2530 lines
246 KiB
XML
2530 lines
246 KiB
XML
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<mods:title id="804D0DB7A36AAF1F5658BF92A021F138">Phytochemistry</mods:title>
|
||
</mods:titleInfo>
|
||
<mods:part id="FE4BA266F906EAD8CF147A2A357D2AC8">
|
||
<mods:date id="7C087C2508D6B6E0D1FA6C429EE1AFB7">2022</mods:date>
|
||
<mods:detail id="7BE68116052A0FBFCC9C58D9CE6FDB0A" type="series">
|
||
<mods:title id="E99041D247E1E69D21FBE1A031D6DE3B">113017</mods:title>
|
||
</mods:detail>
|
||
<mods:detail id="2997E43F374A9BD75938D6505BDE1EBE" type="pubDate">
|
||
<mods:number id="D5F4F2123E3040827B8843C688079489">2022-02-28</mods:number>
|
||
</mods:detail>
|
||
<mods:detail id="DC72B55ED5AEFB946C07E2981565508A" type="volume">
|
||
<mods:number id="9937E9EE269A05C4FD2F24D6D12F8C17">194</mods:number>
|
||
</mods:detail>
|
||
<mods:extent id="D4E7EE5FF77F4D4F69328B1DCCA4E4D3" unit="page">
|
||
<mods:start id="43114C1C7380F93C9B6619458525B29B">1</mods:start>
|
||
<mods:end id="3AF061C0D5A3B1CF6A80BB3B58CAB75C">13</mods:end>
|
||
</mods:extent>
|
||
</mods:part>
|
||
</mods:relatedItem>
|
||
<mods:location id="E9B437832B57CA2F7C662AE39CBAC303">
|
||
<mods:url id="2AC109AE3039258B0DB570062E0D47D0">http://dx.doi.org/10.1016/j.phytochem.2021.113017</mods:url>
|
||
</mods:location>
|
||
<mods:classification id="87B5E13FBC63F833405A63AA010F45CC">journal article</mods:classification>
|
||
<mods:identifier id="9F18A7335DD35378E5D0B85E0617662A" type="DOI">10.1016/j.phytochem.2021.113017</mods:identifier>
|
||
<mods:identifier id="56007B2C7CADC13DF2E3E951B65B99C2" type="GBIF-Dataset">bc4a0634-4be4-45eb-a6fa-cd2f606da47f</mods:identifier>
|
||
<mods:identifier id="C61BBA5DD9661291EC131A42BE681009" type="ISSN">1873-3700</mods:identifier>
|
||
<mods:identifier id="CEDF0FF44B26EACFA2EB62A18729E61E" type="Zenodo-Dep">8240066</mods:identifier>
|
||
</mods:mods>
|
||
<treatment id="7F122842D13AFFEAFFFDF8DDFAFEF82E" ID-DOI="http://doi.org/10.5281/zenodo.8239997" ID-Zenodo-Dep="8239997" LSID="urn:lsid:plazi:treatment:7F122842D13AFFEAFFFDF8DDFAFEF82E" httpUri="http://treatment.plazi.org/id/7F122842D13AFFEAFFFDF8DDFAFEF82E" lastPageId="9" lastPageNumber="10" pageId="1" pageNumber="2">
|
||
<subSubSection id="BFA1CADFD13AFFE2FFFDF8DDFD96F8FA" box="[100,537,1878,1898]" pageId="1" pageNumber="2" type="nomenclature">
|
||
<paragraph id="F7049954D13AFFE2FFFDF8DDFD96F8FA" blockId="1.[100,537,1878,1898]" box="[100,537,1878,1898]" pageId="1" pageNumber="2">
|
||
<heading id="AC4C2E38D13AFFE2FFFDF8DDFD96F8FA" bold="true" box="[100,537,1878,1898]" fontSize="36" level="1" pageId="1" pageNumber="2" reason="1">
|
||
<emphasis id="C5CF4546D13AFFE2FFFDF8DDFD96F8FA" bold="true" box="[100,537,1878,1898]" italics="true" pageId="1" pageNumber="2">
|
||
2.1. Phytochemical investigation of
|
||
<taxonomicName id="30BBE2D7D13AFFE2FE32F8DDFD96F8FA" ID-CoL="5BFGJ" ID-ENA="60093" authorityName="L." box="[427,537,1879,1898]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="minor">Vinca minor</taxonomicName>
|
||
</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
</subSubSection>
|
||
<subSubSection id="BFA1CADFD13AFFE7FF1DF805FDF8F90A" lastPageId="4" lastPageNumber="5" pageId="1" pageNumber="2" type="description">
|
||
<paragraph id="F7049954D13AFFE2FF1DF805FA5FFC7C" blockId="1.[100,770,1935,1982]" lastBlockId="1.[818,1488,148,1982]" pageId="1" pageNumber="2">
|
||
GC-MS analysis of the alkaloid extract of
|
||
<taxonomicName id="30BBE2D7D13AFFE2FD88F805FDEFF832" box="[529,608,1935,1954]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="minor">
|
||
<emphasis id="C5CF4546D13AFFE2FD88F805FDEFF832" bold="true" box="[529,608,1935,1954]" italics="true" pageId="1" pageNumber="2">V. minor</emphasis>
|
||
</taxonomicName>
|
||
led to the initial identification of monoterpene indole alkaloids. Moreover, this extract showed interesting human cholinesterases inhibition activities (IC
|
||
<subScript id="6B3F9B11D13AFFE2FA33FF11FA33FF39" attach="right" box="[1450,1468,155,169]" fontSize="6" pageId="1" pageNumber="2">50</subScript>
|
||
,
|
||
<emphasis id="C5CF4546D13AFFE2FA5BFF11FCD6FF55" bold="true" italics="true" pageId="1" pageNumber="2">
|
||
<subScript id="6B3F9B11D13AFFE2FA5BFF11FCD6FF55" attach="none" fontSize="6" pageId="1" pageNumber="2">hAChE</subScript>
|
||
</emphasis>
|
||
= 191.58 ± 38.03 μg/mL; IC
|
||
<subScript id="6B3F9B11D13AFFE2FBF4FF3DFBF0FF55" attach="right" box="[1133,1151,183,197]" fontSize="6" pageId="1" pageNumber="2">50</subScript>
|
||
,
|
||
<subScript id="6B3F9B11D13AFFE2FB1CFF3CFB33FF55" attach="left" box="[1157,1212,182,197]" fontSize="6" pageId="1" pageNumber="2">
|
||
<emphasis id="C5CF4546D13AFFE2FB1CFF3CFB02FF54" bold="true" box="[1157,1165,182,196]" italics="true" pageId="1" pageNumber="2">h</emphasis>
|
||
BuChE
|
||
</subScript>
|
||
= 13.60 ± 0.82 μg/mL). The promising bioactivities of the indole alkaloids, together with the absence of a detailed up-to-date phytochemical report on
|
||
<taxonomicName id="30BBE2D7D13AFFE2FA9EFF62FADAFF6A" box="[1287,1365,231,251]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="minor">
|
||
<emphasis id="C5CF4546D13AFFE2FA9EFF62FADAFF6A" bold="true" box="[1287,1365,231,251]" italics="true" pageId="1" pageNumber="2">V. minor</emphasis>
|
||
</taxonomicName>
|
||
, encouraged us to examine this species. Extensive chromatographic purification led to the isolation of twenty-two known and one undescribed indole alkaloids (
|
||
<figureCitation id="6F8085D1D13AFFE2FC1AFEB1FC37FEDE" box="[899,952,315,334]" captionStart="Fig" captionStartId="2.[446,476,1364,1381]" captionTargetBox="[208,1380,148,1337]" captionTargetPageId="2" captionText="Fig. 1. Chemical structures of isolated alkaloids from aerial parts of Vinca minor." figureDoi="http://doi.org/10.5281/zenodo.8240068" httpUri="https://zenodo.org/record/8240068/files/figure.png" pageId="1" pageNumber="2">Fig. 1</figureCitation>
|
||
). The known alkaloids were identified by comparison of their MS, ESI-HRMS, 1D and 2D NMR data with the literature as vincaminorine (
|
||
<emphasis id="C5CF4546D13AFFE2FC32FEF9FC38FE16" bold="true" box="[939,951,371,390]" pageId="1" pageNumber="2">1</emphasis>
|
||
) (Farahanikia et al., 2011; Tan et al., 2016), eburnamonine (
|
||
<emphasis id="C5CF4546D13AFFE2FCF4FE05FCF6FE32" bold="true" box="[877,889,399,418]" pageId="1" pageNumber="2">3</emphasis>
|
||
) (Kovacik and Kompiˇs, 1969; Li et al., 2019), minovine (
|
||
<emphasis id="C5CF4546D13AFFE2FA22FE05FA48FE32" bold="true" box="[1467,1479,399,418]" pageId="1" pageNumber="2">4</emphasis>
|
||
) (Farahanikia et al., 2011; Tan et al., 2016), vincatine (
|
||
<emphasis id="C5CF4546D13AFFE2FA0AFE20FA10FE2D" bold="true" box="[1427,1439,426,445]" pageId="1" pageNumber="2">6</emphasis>
|
||
, diastereoisomers 3:2) (Ali et al., 1982; Danieli et al., 1984; D¨oepke et al., 1969), minovincine (
|
||
<emphasis id="C5CF4546D13AFFE2FC65FE69FB87FE66" bold="true" box="[1020,1032,483,502]" pageId="1" pageNumber="2">7</emphasis>
|
||
) (Farahanikia et al., 2011; Kalaus et al., 1997; Laforteza et al., 2013; Varga et al., 2020), demethoxyalstonamide (
|
||
<emphasis id="C5CF4546D13AFFE2FA37FE74FA48FD81" bold="true" box="[1454,1479,510,529]" pageId="1" pageNumber="2">10</emphasis>
|
||
) (Ur-Rahman et al., 1991a), vincorine (
|
||
<emphasis id="C5CF4546D13AFFE2FB36FD90FB47FDBD" bold="true" box="[1199,1224,538,557]" pageId="1" pageNumber="2">11</emphasis>
|
||
) (Horning and MacMillan, 2013; Mokrý et al., 1962), minovincinine (
|
||
<emphasis id="C5CF4546D13AFFE2FB45FDBCFB7AFDD9" bold="true" box="[1244,1269,566,585]" pageId="1" pageNumber="2">12</emphasis>
|
||
) (D¨oepke and Meisel, 1970; Plat et al., 1962; Williams et al., 2019; Zeng et al., 2020), aspidospermidine (
|
||
<emphasis id="C5CF4546D13AFFE2FC58FDE4FC55FD11" bold="true" box="[961,986,622,641]" pageId="1" pageNumber="2">13</emphasis>
|
||
) (Kim et al., 2017; Ma et al., 2015; Xu et al., 2019), 19-oxoeburnamonine (
|
||
<emphasis id="C5CF4546D13AFFE2FB95FD00FBAAFD0D" bold="true" box="[1036,1061,650,669]" pageId="1" pageNumber="2">14</emphasis>
|
||
) (Kitajima et al., 2014), akuammicine (
|
||
<emphasis id="C5CF4546D13AFFE2FA37FD00FA48FD0D" bold="true" box="[1454,1479,650,669]" pageId="1" pageNumber="2">15</emphasis>
|
||
) (Hong and Vanderwal, 2017), tubotaiwine (
|
||
<emphasis id="C5CF4546D13AFFE2FB43FD2CFB7CFD29" bold="true" box="[1242,1267,678,697]" pageId="1" pageNumber="2">16</emphasis>
|
||
) (Martin et al., 2011), aspidofractinine (
|
||
<emphasis id="C5CF4546D13AFFE2FC7DFD4BFC72FD44" bold="true" box="[996,1021,705,724]" pageId="1" pageNumber="2">18</emphasis>
|
||
) (Varga et al., 2020), 2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1
|
||
<emphasis id="C5CF4546D13AFFE2FC6AFD54FB8DFD61" bold="true" box="[1011,1026,734,753]" italics="true" pageId="1" pageNumber="2">H</emphasis>
|
||
-indole (
|
||
<emphasis id="C5CF4546D13AFFE2FBC2FD57FBFBFD60" bold="true" box="[1115,1140,733,752]" pageId="1" pageNumber="2">19</emphasis>
|
||
) (Ur-Rahman et al., 1991b), 14, 15-dihydrovindolinine (
|
||
<emphasis id="C5CF4546D13AFFE2FB8CFD73FBA1FC9C" bold="true" box="[1045,1070,761,780]" pageId="1" pageNumber="2">20</emphasis>
|
||
) (Yagudaev, 1984), strictamine (
|
||
<emphasis id="C5CF4546D13AFFE2FAF7FD73FA08FC9C" bold="true" box="[1390,1415,761,780]" pageId="1" pageNumber="2">21</emphasis>
|
||
) (Chen et al., 2018), and 5-oxoaspidofractinine (
|
||
<emphasis id="C5CF4546D13AFFE2FB2EFC9FFB5FFCB8" bold="true" box="[1207,1232,789,808]" pageId="1" pageNumber="2">22</emphasis>
|
||
) (Wenkert and Liu, 1994). The NMR data for previously described alkaloids vincaminoreine (
|
||
<emphasis id="C5CF4546D13AFFE2FA22FCBBFA48FCD4" bold="true" box="[1467,1479,817,836]" pageId="1" pageNumber="2">2</emphasis>
|
||
) (Farahanikia et al., 2011), 16-methoxyminovine (
|
||
<emphasis id="C5CF4546D13AFFE2FA84FCC7FAA6FCF0" bold="true" box="[1309,1321,845,864]" pageId="1" pageNumber="2">5</emphasis>
|
||
) (Kuehne et al., 1979), 16-methoxyminovincine (
|
||
<emphasis id="C5CF4546D13AFFE2FBE8FCE3FBF2FCEC" bold="true" box="[1137,1149,873,892]" pageId="1" pageNumber="2">8</emphasis>
|
||
) (Plat et al., 1962), raucubainine (
|
||
<emphasis id="C5CF4546D13AFFE2FCA3FC0FFCDCFC08" bold="true" box="[826,851,901,920]" pageId="1" pageNumber="2">17</emphasis>
|
||
) (Sierra et al., 1982), and raucubaine (
|
||
<emphasis id="C5CF4546D13AFFE2FB59FC0FFB56FC08" bold="true" box="[1216,1241,901,920]" pageId="1" pageNumber="2">23</emphasis>
|
||
) (Sierra et al., 1982) have been revised, corrected and missing data added. The newly isolated alkaloid was named vincaminorudeine (
|
||
<emphasis id="C5CF4546D13AFFE2FB32FC37FB38FC40" bold="true" box="[1195,1207,957,976]" pageId="1" pageNumber="2">9</emphasis>
|
||
). Alkaloids
|
||
<emphasis id="C5CF4546D13AFFE2FAB0FC37FABAFC40" bold="true" box="[1321,1333,957,976]" pageId="1" pageNumber="2">5</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D13AFFE2FAD8FC37FAD5FC40" bold="true" box="[1345,1370,957,976]" pageId="1" pageNumber="2">10</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D13AFFE2FAFFFC37FAF0FC40" bold="true" box="[1382,1407,957,976]" pageId="1" pageNumber="2">13</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D13AFFE2FA12FC37FA2BFC40" bold="true" box="[1419,1444,957,976]" pageId="1" pageNumber="2">14</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D13AFFE2FA29FC37FA46FC40" bold="true" box="[1456,1481,957,976]" pageId="1" pageNumber="2">16</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D13AFFE2FCABFC52FCE1FC7B" bold="true" box="[818,878,984,1004]" pageId="1" pageNumber="2">17–20</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D13AFFE2FCE3FC52FC1CFC7B" bold="true" box="[890,915,984,1003]" pageId="1" pageNumber="2">22</emphasis>
|
||
, and
|
||
<emphasis id="C5CF4546D13AFFE2FC50FC52FC6DFC7B" bold="true" box="[969,994,984,1003]" pageId="1" pageNumber="2">23</emphasis>
|
||
are herein reported for the first time in this species.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13AFFE2FCC8FC7EFB63FA3A" blockId="1.[818,1488,148,1982]" pageId="1" pageNumber="2">
|
||
Alkaloid
|
||
<emphasis id="C5CF4546D13AFFE2FC3EFC7EFC4FFB97" bold="true" box="[935,960,1012,1031]" pageId="1" pageNumber="2">10</emphasis>
|
||
was previously isolated from
|
||
<taxonomicName id="30BBE2D7D13AFFE2FB42FC7EFB11FBB4" authority="Wall. ex G. Don (Ur-Rahman et al., 1991 a)" class="Magnoliopsida" family="Apocynaceae" genus="Alstonia" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="macrophylla">
|
||
<emphasis id="C5CF4546D13AFFE2FB42FC7EFA17FB97" bold="true" box="[1243,1432,1012,1031]" italics="true" pageId="1" pageNumber="2">Alstonia macrophylla</emphasis>
|
||
Wall. ex G. Don (Ur-Rahman et al., 1991a)
|
||
</taxonomicName>
|
||
. Alkaloid
|
||
<emphasis id="C5CF4546D13AFFE2FA9BFB9AFA94FBB3" bold="true" box="[1282,1307,1040,1059]" pageId="1" pageNumber="2">13</emphasis>
|
||
was isolated from
|
||
<taxonomicName id="30BBE2D7D13AFFE2FCABFBA6FA9EFBAF" authority="Lour (Shi et al., 2019)" box="[818,1297,1068,1088]" class="Magnoliopsida" family="Apocynaceae" genus="Tabernaemontana" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="bufalina">
|
||
<emphasis id="C5CF4546D13AFFE2FCABFBA6FBA9FBAF" bold="true" box="[818,1062,1068,1087]" italics="true" pageId="1" pageNumber="2">Tabernaemontana bufalina</emphasis>
|
||
Lour (Shi et al., 2019)
|
||
</taxonomicName>
|
||
. and
|
||
<taxonomicName id="30BBE2D7D13AFFE2FAD5FBA6FBFBFBCB" authority="Decne. (Abdel-Mogib et al., 1998)" class="Magnoliopsida" family="Apocynaceae" genus="Rhazya" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="stricta">
|
||
<emphasis id="C5CF4546D13AFFE2FAD5FBA6FA5FFBAF" bold="true" box="[1356,1488,1068,1087]" italics="true" pageId="1" pageNumber="2">Rhazya stricta</emphasis>
|
||
Decne. (Abdel-Mogib et al., 1998)
|
||
</taxonomicName>
|
||
, as well as alkaloid
|
||
<emphasis id="C5CF4546D13AFFE2FAACFBC2FAC1FBCB" bold="true" box="[1333,1358,1096,1115]" pageId="1" pageNumber="2">18</emphasis>
|
||
and its structural
|
||
<typeStatus id="280027F6D13AFFE2FCFAFBEEFC18FBE7" box="[867,919,1124,1143]" pageId="1" pageNumber="2">types</typeStatus>
|
||
, which can be also found in
|
||
<taxonomicName id="30BBE2D7D13AFFE2FB03FBEEFA8EFBE7" box="[1178,1281,1124,1143]" class="Magnoliopsida" family="Apocynaceae" genus="Kopsia" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="undetermined">
|
||
<emphasis id="C5CF4546D13AFFE2FB03FBEEFB59FBE7" bold="true" box="[1178,1238,1124,1143]" italics="true" pageId="1" pageNumber="2">Kopsia</emphasis>
|
||
spp.
|
||
</taxonomicName>
|
||
(Kitajima et al., 2014; Wong et al., 2021).
|
||
<taxonomicName id="30BBE2D7D13AFFE2FC74FB0AFBD9FB03" box="[1005,1110,1152,1171]" class="Magnoliopsida" family="Apocynaceae" genus="Kopsia" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="undetermined">
|
||
<emphasis id="C5CF4546D13AFFE2FC74FB0AFBA6FB03" bold="true" box="[1005,1065,1152,1171]" italics="true" pageId="1" pageNumber="2">Kopsia</emphasis>
|
||
spp.
|
||
</taxonomicName>
|
||
is also a source of alkaloid
|
||
<emphasis id="C5CF4546D13AFFE2FAC1FB0AFAFEFB03" bold="true" box="[1368,1393,1152,1171]" pageId="1" pageNumber="2">14</emphasis>
|
||
(Kitajima et al., 2014). Alkaloid
|
||
<emphasis id="C5CF4546D13AFFE2FB95FB16FBAAFB3F" bold="true" box="[1036,1061,1180,1199]" pageId="1" pageNumber="2">16</emphasis>
|
||
was obtained, for example, from
|
||
<taxonomicName id="30BBE2D7D13AFFE2FAF5FB16FC54FB5B" authority="(Shi et al., 2019)" baseAuthorityName="Shi" baseAuthorityYear="2019" class="Magnoliopsida" family="Apocynaceae" genus="Tabernaemontana" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="bufalina">
|
||
<emphasis id="C5CF4546D13AFFE2FAF5FB16FA40FB3E" bold="true" box="[1388,1487,1179,1199]" italics="true" pageId="1" pageNumber="2">T. bufalina</emphasis>
|
||
(Shi et al., 2019)
|
||
</taxonomicName>
|
||
, as well as from
|
||
<taxonomicName id="30BBE2D7D13AFFE2FB13FB3DFC7EFB77" authority="L. D. Benson (Mroue et al., 1996)" class="Magnoliopsida" family="Apocynaceae" genus="Haplophyton" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="crooksii">
|
||
<emphasis id="C5CF4546D13AFFE2FB13FB3DFAC5FB5A" bold="true" box="[1162,1354,1207,1226]" italics="true" pageId="1" pageNumber="2">Haplophyton crooksii</emphasis>
|
||
L. D. Benson (Mroue et al., 1996)
|
||
</taxonomicName>
|
||
.
|
||
<taxonomicName id="30BBE2D7D13AFFE2FC62FB59FB7AFB77" authority="Griseb." authorityName="Griseb." box="[1019,1269,1235,1255]" class="Magnoliopsida" family="Apocynaceae" genus="Rauvolfia" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="salicifolia">
|
||
<emphasis id="C5CF4546D13AFFE2FC62FB59FB23FB76" bold="true" box="[1019,1196,1235,1254]" italics="true" pageId="1" pageNumber="2">Rauvolfia salicifolia</emphasis>
|
||
Griseb.
|
||
</taxonomicName>
|
||
is a source of alkaloids
|
||
<emphasis id="C5CF4546D13AFFE2FCABFB65FCC4FA92" bold="true" box="[818,843,1263,1282]" pageId="1" pageNumber="2">17</emphasis>
|
||
and
|
||
<emphasis id="C5CF4546D13AFFE2FCE1FB65FC1EFA92" bold="true" box="[888,913,1263,1282]" pageId="1" pageNumber="2">23</emphasis>
|
||
(Sierra et al., 1982). Alkaloid
|
||
<emphasis id="C5CF4546D13AFFE2FB33FB65FB4CFA92" bold="true" box="[1194,1219,1263,1282]" pageId="1" pageNumber="2">23</emphasis>
|
||
can also be found in
|
||
<taxonomicName id="30BBE2D7D13AFFE2FA1FFB65FB61FA8E" authority="(G. Forst.) R. Br. (Jacquier et al., 1982)" class="Magnoliopsida" family="Apocynaceae" genus="Alstonia" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="costata">
|
||
<emphasis id="C5CF4546D13AFFE2FA1FFB65FCFEFA8F" bold="true" italics="true" pageId="1" pageNumber="2">Alstonia costata</emphasis>
|
||
(G. Forst.) R. Br. (Jacquier et al., 1982)
|
||
</taxonomicName>
|
||
. Alkaloid
|
||
<emphasis id="C5CF4546D13AFFE2FAD7FA81FAE8FA8E" bold="true" box="[1358,1383,1291,1310]" pageId="1" pageNumber="2">20</emphasis>
|
||
was previously isolated from other
|
||
<taxonomicName id="30BBE2D7D13AFFE2FB84FAADFBF3FAAB" box="[1053,1148,1319,1339]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="1" pageNumber="2" phylum="Tracheophyta" rank="species" species="undetermined">
|
||
<emphasis id="C5CF4546D13AFFE2FB84FAADFBDFFAAA" bold="true" box="[1053,1104,1319,1338]" italics="true" pageId="1" pageNumber="2">Vinca</emphasis>
|
||
spp.
|
||
</taxonomicName>
|
||
(Abdurakhimova et al., 1967). All of the mentioned plants belong to the Apocynacae family. So far, alkaloids
|
||
<emphasis id="C5CF4546D13AFFE2FCABFAD5FCB1FAE2" bold="true" box="[818,830,1375,1394]" pageId="1" pageNumber="2">5</emphasis>
|
||
and
|
||
<emphasis id="C5CF4546D13AFFE2FCE9FAD5FC06FAE2" bold="true" box="[880,905,1375,1394]" pageId="1" pageNumber="2">22</emphasis>
|
||
have not been found in a natural source, but were prepared synthetically (Kuehne et al., 1979; Wenkert and Liu, 1994). The most active alkaloid (
|
||
<emphasis id="C5CF4546D13AFFE2FC53FA1DFC64FA3A" bold="true" box="[970,1003,1431,1450]" pageId="1" pageNumber="2">19)</emphasis>
|
||
is discussed in detail later.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13AFFE2FCC8FA39FB13F9C1" blockId="1.[818,1488,148,1982]" pageId="1" pageNumber="2">
|
||
The undescribed monoterpene alkaloid (
|
||
<emphasis id="C5CF4546D13AFFE2FB50FA39FB5AFA56" bold="true" box="[1225,1237,1459,1478]" pageId="1" pageNumber="2">9</emphasis>
|
||
) exhibited a molecular ion peak [M+ H]
|
||
<superScript id="00CE341CD13AFFE2FC35FA41FC39FA47" attach="left" box="[940,950,1483,1495]" fontSize="6" pageId="1" pageNumber="2">+</superScript>
|
||
at
|
||
<emphasis id="C5CF4546D13AFFE2FC47FA45FB8DFA72" bold="true" box="[990,1026,1487,1506]" italics="true" pageId="1" pageNumber="2">m/z</emphasis>
|
||
371.2339, matching the formula C
|
||
<subScript id="6B3F9B11D13AFFE2FAC7FA5CFAFFFA74" attach="both" box="[1374,1392,1494,1508]" fontSize="6" pageId="1" pageNumber="2">22</subScript>
|
||
H
|
||
<subScript id="6B3F9B11D13AFFE2FA19FA5CFA1DFA74" attach="both" box="[1408,1426,1494,1508]" fontSize="6" pageId="1" pageNumber="2">30</subScript>
|
||
N
|
||
<subScript id="6B3F9B11D13AFFE2FA38FA5CFA25FA74" attach="both" box="[1441,1450,1494,1508]" fontSize="6" pageId="1" pageNumber="2">2</subScript>
|
||
O
|
||
<subScript id="6B3F9B11D13AFFE2FA23FA5CFA4CFA74" attach="left" box="[1466,1475,1494,1508]" fontSize="6" pageId="1" pageNumber="2">3</subScript>
|
||
<superScript id="00CE341CD13AFFE2FA5AFA41FA42FA47" attach="right" box="[1475,1485,1483,1495]" fontSize="6" pageId="1" pageNumber="2">+</superScript>
|
||
(calc. 371.2329). The compound was isolated as light brown crystals, but, unfortunately, not in sufficient quantity for X-ray diffraction analysis. Moreover, none of the circular dichroism data for compounds with the required similarity were available.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13AFFE1FCC8F9D0FB73F8B8" blockId="1.[818,1488,148,1982]" lastBlockId="2.[818,1488,1422,1972]" lastPageId="2" lastPageNumber="3" pageId="1" pageNumber="2">
|
||
However, the chemical constitution of
|
||
<emphasis id="C5CF4546D13AFFE2FB49F9D0FB53F9FD" bold="true" box="[1232,1244,1626,1645]" pageId="1" pageNumber="2">9</emphasis>
|
||
was elucidated by NMR analysis. The
|
||
<superScript id="00CE341CD13AFFE2FC2DF9FAFC32F9EE" attach="right" box="[948,957,1648,1662]" fontSize="6" pageId="1" pageNumber="2">1</superScript>
|
||
H NMR spectrum revealed four signals of aromatic protons with a characteristic splitting pattern for a 1,2-disubstituted benzene ring (
|
||
<subScript id="6B3F9B11D13AFFE2FC0DF924FC25F953" attach="left" box="[916,938,1710,1731]" fontSize="6" pageId="1" pageNumber="2">δH</subScript>
|
||
7.53, dd,
|
||
<emphasis id="C5CF4546D13AFFE2FB9CF924FB80F951" bold="true" box="[1029,1039,1710,1729]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 7.8 Hz,
|
||
<emphasis id="C5CF4546D13AFFE2FBE9F924FBF5F951" bold="true" box="[1136,1146,1710,1729]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 1.1 Hz, H-14; 7.27, dd,
|
||
<emphasis id="C5CF4546D13AFFE2FAF3F924FAFBF951" bold="true" box="[1386,1396,1710,1729]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 7.8 Hz,
|
||
<emphasis id="C5CF4546D13AFFE2FCABF940FCB3F94D" bold="true" box="[818,828,1738,1757]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 1.1 Hz, H-17; 7.19, td,
|
||
<emphasis id="C5CF4546D13AFFE2FBB3F940FBBBF94D" bold="true" box="[1066,1076,1738,1757]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 7.8 Hz,
|
||
<emphasis id="C5CF4546D13AFFE2FB0CF940FB10F94D" bold="true" box="[1173,1183,1738,1757]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 1.1 Hz, H-16; 7.09, td,
|
||
<emphasis id="C5CF4546D13AFFE2FA14F940FA18F94D" bold="true" box="[1421,1431,1738,1757]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 7.8 Hz,
|
||
<emphasis id="C5CF4546D13AFFE2FCC1F96CFCEDF969" bold="true" box="[856,866,1766,1785]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 1.1 Hz, H-15), and one methine α- proton (
|
||
<subScript id="6B3F9B11D13AFFE2FA8BF96CFAA7F96B" attach="left" box="[1298,1320,1766,1787]" fontSize="6" pageId="1" pageNumber="2">δH</subScript>
|
||
4.39, dd,
|
||
<emphasis id="C5CF4546D13AFFE2FA13F96CFA1BF969" bold="true" box="[1418,1428,1766,1785]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 4.3 Hz,
|
||
<emphasis id="C5CF4546D13AFFE2FCC5F888FCE9F885" bold="true" box="[860,870,1794,1813]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 2.7 Hz, H-3), the chemical shift of which was crucial for determining the relative configuration of this stereocenter (see
|
||
<tableCitation id="BA39ACEFD13AFFE2FA1AF897FA46F8A1" box="[1411,1481,1821,1841]" captionStart="Table 1" captionStartId="3.[100,150,150,166]" captionTargetPageId="3" captionText="Table 1 Key correlations from 2D NMR experiments in the structure elucidation of undescribed alkaloid 9 (HMBC interaction – blue arrow; H2BC and COSY interaction – red bond) and its 1H and 13C NMR chemical shifts assigned to the related position in ppm with coupling constants (in parenthesis, reported in Hz).." httpUri="http://table.plazi.org/id/A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D" pageId="1" pageNumber="2" tableUuid="A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D">Table 1</tableCitation>
|
||
,
|
||
<figureCitation id="6F8085D1D13AFFE2FCABF8B3FCE7F8DC" box="[818,872,1849,1868]" captionStart="Fig" captionStartId="4.[100,130,1146,1163]" captionTargetBox="[209,1379,148,1118]" captionTargetId="graphics-578@4.[209,1379,148,1118]" captionTargetPageId="4" captionText="Fig. 2. Indole alkaloids with a quebrachamine framework previously described in the literature employing at least 1H NMR analysis. The difference in the H-3 chemical shift of 3-epimers can be valuable for distinguishing between these diastereomers, which is highlighted. It must be mentioned that the C-3 configuration for all compounds shown was described to the contrary in Kutney’s article (Kutney et al., 1975). However, the correct configuration of these alkaloids had already been identified by Kompisˇet al. (1968)." figureDoi="http://doi.org/10.5281/zenodo.8240070" httpUri="https://zenodo.org/record/8240070/files/figure.png" pageId="1" pageNumber="2">Fig. 2</figureCitation>
|
||
, respectively). A deshielded singlet (
|
||
<subScript id="6B3F9B11D13AFFE2FB52F8B3FB6DF8DF" attach="left" box="[1227,1250,1849,1871]" fontSize="6" pageId="1" pageNumber="2">δH</subScript>
|
||
3.72, s, 3-COOCH
|
||
<subScript id="6B3F9B11D13AFFE2FA0AF8CBFA13F8DF" attach="left" box="[1427,1436,1857,1871]" fontSize="6" pageId="1" pageNumber="2">3</subScript>
|
||
) was also observed, corresponding to a methyl ester group overlapped with a multiplet of a one proton diastereotopic methylene group (
|
||
<subScript id="6B3F9B11D13AFFE2FAC9F8FBFAE9F817" attach="left" box="[1360,1382,1905,1927]" fontSize="6" pageId="1" pageNumber="2">δH</subScript>
|
||
3.75–3.70, m, H-19), as well as characteristic signals of the 1-hydroxyethyl group (
|
||
<subScript id="6B3F9B11D13AFFE2FCA3F823FCDFF82E" attach="left" box="[826,848,1961,1982]" fontSize="6" pageId="1" pageNumber="2">δH</subScript>
|
||
3.47, q,
|
||
<emphasis id="C5CF4546D13AFFE2FC3FF823FC3FF82C" bold="true" box="[934,944,1961,1980]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 6.5 Hz, H-20; 1.29, d, overlap,
|
||
<emphasis id="C5CF4546D13AFFE2FB6FF823FA8FF82C" bold="true" box="[1270,1280,1961,1980]" italics="true" pageId="1" pageNumber="2">J</emphasis>
|
||
= 6.5 Hz, H-21). The signal of this methyl group overlapped with a multiplet of two protons (
|
||
<subScript id="6B3F9B11D139FFE1FFF5FA20FF0CFA50" attach="left" box="[108,131,1450,1472]" fontSize="6" pageId="2" pageNumber="3">δH</subScript>
|
||
1.36–1.21, m, overlap, H-7, H-6). Resonances of another eight protons were further recognized. In the
|
||
<superScript id="00CE341CD139FFE1FE4CFA4AFE68FA5E" attach="right" box="[469,487,1472,1486]" fontSize="6" pageId="2" pageNumber="3">13</superScript>
|
||
C NMR spectrum, 21 carbon signals were observed: specific chemical shifts for a methyl ester group (
|
||
<subScript id="6B3F9B11D139FFE1FFF5FA74FF0EF983" attach="left" box="[108,129,1534,1555]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
177.0 and 52.7, 3-COOCH
|
||
<subScript id="6B3F9B11D139FFE1FEE5F98FFE0AF983" attach="left" box="[380,389,1541,1555]" fontSize="6" pageId="2" pageNumber="3">3</subScript>
|
||
), four quaternary sp
|
||
<superScript id="00CE341CD139FFE1FDDFFA72FDC0F996" attach="right" box="[582,591,1528,1542]" fontSize="6" pageId="2" pageNumber="3">2</superScript>
|
||
-carbons (
|
||
<subScript id="6B3F9B11D139FFE1FD35FA74FD4EF983" attach="left" box="[684,705,1534,1555]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
139.1, C-2; 136.7, C-18; 127.0, C-13; 110.3, C-12), four protonated sp
|
||
<superScript id="00CE341CD139FFE1FD30F99EFD3DF9B2" attach="left" box="[681,690,1556,1570]" fontSize="6" pageId="2" pageNumber="3">2</superScript>
|
||
-carbons (
|
||
<subScript id="6B3F9B11D139FFE1FFF5F9BCFF0EF9DB" attach="left" box="[108,129,1590,1611]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
120.7, C-16; 118.5, C-15; 118.1, C-14; 108.6, C-17), a deshielded
|
||
<emphasis id="C5CF4546D139FFE1FD75F9BCFD74F9D9" bold="true" box="[748,763,1590,1609]" italics="true" pageId="2" pageNumber="3">O</emphasis>
|
||
- methine group (
|
||
<subScript id="6B3F9B11D139FFE1FF60F9D8FE81F9F7" attach="left" box="[249,270,1618,1639]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
74.2, C-20), three
|
||
<emphasis id="C5CF4546D139FFE1FE23F9D8FE46F9F5" bold="true" box="[442,457,1618,1637]" italics="true" pageId="2" pageNumber="3">N</emphasis>
|
||
-methylene groups (
|
||
<subScript id="6B3F9B11D139FFE1FD1BF9D8FD18F9F7" attach="left" box="[642,663,1618,1639]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
56.6, C-19; 55.2, C-8; 53.6, C-10), one quaternary sp
|
||
<superScript id="00CE341CD139FFE1FE6DF9E2FE72F9E6" attach="right" box="[500,509,1640,1654]" fontSize="6" pageId="2" pageNumber="3">3</superScript>
|
||
-carbon (
|
||
<subScript id="6B3F9B11D139FFE1FDCDF9E4FDE6F913" attach="left" box="[596,617,1646,1667]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
42.9, C-5), one α- carbon (
|
||
<subScript id="6B3F9B11D139FFE1FF5CF903FF56F90F" attach="left" box="[197,217,1673,1695]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
38.7, C-3), four methylene groups (
|
||
<subScript id="6B3F9B11D139FFE1FDB2F903FDB0F90F" attach="left" box="[555,575,1673,1695]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
31.7, C-6; 31.1, C-4; 22.3, C-11; 22.3, C-7), one
|
||
<emphasis id="C5CF4546D139FFE1FEE9F92FFEF0F928" bold="true" box="[368,383,1701,1720]" italics="true" pageId="2" pageNumber="3">N</emphasis>
|
||
-methyl (
|
||
<subScript id="6B3F9B11D139FFE1FE41F92FFE63F92B" attach="left" box="[472,492,1701,1723]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
30.3, 1-
|
||
<collectingCountry id="8FACD9C4D139FFE1FDA3F92FFDD3F928" box="[570,604,1701,1720]" name="Switzerland" pageId="2" pageNumber="3">CH</collectingCountry>
|
||
<subScript id="6B3F9B11D139FFE1FDC4F927FDE9F92B" attach="right" box="[605,614,1709,1723]" fontSize="6" pageId="2" pageNumber="3">3</subScript>
|
||
), and one more shielded methyl (
|
||
<subScript id="6B3F9B11D139FFE1FE92F94BFEAFF946" attach="left" box="[267,288,1729,1750]" fontSize="6" pageId="2" pageNumber="3">δC</subScript>
|
||
17.6, C-21). Every individual signal of the proton and carbon NMR spectra was unambiguously assigned to specific groups employing HSQC experiment. Coupled spin systems were identified by correlations in the COSY and H2BC spectra, and then the
|
||
<emphasis id="C5CF4546D139FFE1FD3DF89FFD3CF8B8" bold="true" box="[676,691,1813,1832]" italics="true" pageId="2" pageNumber="3">N</emphasis>
|
||
-methylindole moiety and hexahydroazonine cycle were established according to correlations found in the HMBC spectrum. This 9-membered ring condensed with indole is characteristic of quebrachamine-type alkaloids. Furthermore, the propylene connection of the tertiary nitrogen and quaternary carbon C-5 was determined by two-dimensional (2D) NMR experiments. The substituent of C-5 was established by HMBC cross-peaks of H-21/C-5 and H-20/C-19. All related key correlations are depicted in
|
||
<tableCitation id="BA39ACEFD139FFE1FC3AFA4CFC64FA49" box="[931,1003,1478,1497]" captionStart="Table 1" captionStartId="3.[100,150,150,166]" captionTargetPageId="3" captionText="Table 1 Key correlations from 2D NMR experiments in the structure elucidation of undescribed alkaloid 9 (HMBC interaction – blue arrow; H2BC and COSY interaction – red bond) and its 1H and 13C NMR chemical shifts assigned to the related position in ppm with coupling constants (in parenthesis, reported in Hz).." httpUri="http://table.plazi.org/id/A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D" pageId="2" pageNumber="3" tableUuid="A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D">Table 1</tableCitation>
|
||
. Due to several reasons, the relative configuration was determined for all three chiral centers in
|
||
<emphasis id="C5CF4546D139FFE1FA98FA68FA82FA65" bold="true" box="[1281,1293,1506,1525]" pageId="2" pageNumber="3">9</emphasis>
|
||
. Unfortunately, the configuration of the hydroxy methylene C-20 must be left unspecified because of a free rotation of the 1-hydroxy ethylene and the impossibility of using NOESY experiment. Moreover, it was not possible to either derivatize or analyze the compound by X-ray, as mentioned above. At least the stereochemistry of the other two carbons was determined. Because of the many conformations of the 1-azabicyclo [6.3.1]dodec-4-ene moiety, NOESY experiment was not used for the determination of its relative configuration. By comparison of the data for an analogue (
|
||
<emphasis id="C5CF4546D139FFE1FC2DF957FC4FF960" bold="true" box="[948,960,1757,1776]" pageId="2" pageNumber="3">1</emphasis>
|
||
), a structure confirmed by X-ray crystallographic analysis, with that of its diastereomer (
|
||
<emphasis id="C5CF4546D139FFE1FBE4F973FB06F89C" bold="true" box="[1149,1161,1785,1804]" pageId="2" pageNumber="3">2</emphasis>
|
||
), the relative configuration at C-3 and C-5 was determined for
|
||
<emphasis id="C5CF4546D139FFE1FBA6F89FFBC4F8B8" bold="true" box="[1087,1099,1813,1832]" pageId="2" pageNumber="3">9</emphasis>
|
||
(Tan et al., 2016).
|
||
</paragraph>
|
||
<caption id="A3C4C9DCD139FFE1FE27FADEFBFAFAF5" ID-DOI="http://doi.org/10.5281/zenodo.8240068" ID-Zenodo-Dep="8240068" box="[446,1141,1364,1381]" httpUri="https://zenodo.org/record/8240068/files/figure.png" pageId="2" pageNumber="3" startId="2.[446,476,1364,1381]" targetBox="[208,1380,148,1337]" targetPageId="2" targetType="figure">
|
||
<paragraph id="F7049954D139FFE1FE27FADEFBFAFAF5" blockId="2.[446,1141,1364,1381]" box="[446,1141,1364,1381]" pageId="2" pageNumber="3">
|
||
<emphasis id="C5CF4546D139FFE1FE27FADEFE78FAF5" bold="true" box="[446,503,1364,1381]" pageId="2" pageNumber="3">Fig. 1.</emphasis>
|
||
Chemical structures of isolated alkaloids from aerial parts of
|
||
<taxonomicName id="30BBE2D7D139FFE1FB94FADEFBFFFAF5" box="[1037,1136,1364,1381]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="2" pageNumber="3" phylum="Tracheophyta" rank="species" species="minor">
|
||
<emphasis id="C5CF4546D139FFE1FB94FADEFBFFFAF5" bold="true" box="[1037,1136,1364,1381]" italics="true" pageId="2" pageNumber="3">Vinca minor</emphasis>
|
||
</taxonomicName>
|
||
.
|
||
</paragraph>
|
||
</caption>
|
||
<paragraph id="F7049954D139FFE0FCC8F8BBFE23F8EA" blockId="2.[818,1488,1422,1972]" lastBlockId="3.[100,771,1532,1970]" lastPageId="3" lastPageNumber="4" pageId="2" pageNumber="3">
|
||
When comparing the chemical shifts of
|
||
<emphasis id="C5CF4546D139FFE1FB44F8BBFB66F8D4" bold="true" box="[1245,1257,1841,1860]" pageId="2" pageNumber="3">9</emphasis>
|
||
with known analogues without a 20-hydroxy substitution, vincaminorine (
|
||
<emphasis id="C5CF4546D139FFE1FA80F8C7FAAAF8F0" bold="true" box="[1305,1317,1869,1888]" pageId="2" pageNumber="3">1</emphasis>
|
||
) and its 3-epimer vincaminoreine (
|
||
<emphasis id="C5CF4546D139FFE1FC40F8E2FC6AF8EB" bold="true" box="[985,997,1896,1915]" pageId="2" pageNumber="3">2</emphasis>
|
||
), to confirm further the configuration of
|
||
<emphasis id="C5CF4546D139FFE1FA00F8E2FA2AF8EB" bold="true" box="[1433,1445,1896,1915]" pageId="2" pageNumber="3">9</emphasis>
|
||
, an inconsistency was found in the published data. Farahanikia et al. (2011) presented NMR data for
|
||
<emphasis id="C5CF4546D139FFE1FB8FF82AFBADF823" bold="true" box="[1046,1058,1952,1971]" pageId="2" pageNumber="3">1</emphasis>
|
||
and
|
||
<emphasis id="C5CF4546D139FFE1FBC9F82AFBD3F823" bold="true" box="[1104,1116,1952,1971]" pageId="2" pageNumber="3">2</emphasis>
|
||
. Both these alkaloids were also isolated in our work, allowing us to compare the chemical shifts of these molecules. The interpretation of our 1D NMR spectra of
|
||
<emphasis id="C5CF4546D138FFE0FDEBF992FDF1F9BB" bold="true" box="[626,638,1560,1579]" pageId="3" pageNumber="4">1</emphasis>
|
||
matched the published data of
|
||
<emphasis id="C5CF4546D138FFE0FE91F9BEFE9BF9D7" bold="true" box="[264,276,1588,1607]" pageId="3" pageNumber="4">1</emphasis>
|
||
prepared in the enantioselective synthesis (Tan et al., 2016). X-ray analysis confirmed the configuration of
|
||
<quantity id="304334B1D138FFE0FDFEF9DAFD01F9F3" box="[615,654,1616,1635]" metricMagnitude="-2" metricUnit="m" metricValue="2.54" pageId="3" pageNumber="4" unit="in" value="1.0">
|
||
<emphasis id="C5CF4546D138FFE0FDFEF9DAFDFCF9F3" bold="true" box="[615,627,1616,1635]" pageId="3" pageNumber="4">1</emphasis>
|
||
in
|
||
</quantity>
|
||
Tan’ s work (Tan et al., 2016). When the 3-methyl ester and 5-ethyl substituents of
|
||
<emphasis id="C5CF4546D138FFE0FD6CF9E6FC8EF9EF" bold="true" box="[757,769,1644,1663]" pageId="3" pageNumber="4">1</emphasis>
|
||
are
|
||
<emphasis id="C5CF4546D138FFE0FF10F902FF2FF90B" bold="true" box="[137,160,1672,1691]" italics="true" pageId="3" pageNumber="4">cis</emphasis>
|
||
orientated (3
|
||
<emphasis id="C5CF4546D138FFE0FEBBF902FEB7F90B" bold="true" box="[290,312,1672,1691]" italics="true" pageId="3" pageNumber="4">S*</emphasis>
|
||
,5
|
||
<emphasis id="C5CF4546D138FFE0FED3F902FED0F90B" bold="true" box="[330,351,1672,1691]" italics="true" pageId="3" pageNumber="4">S*</emphasis>
|
||
), the chemical shift of the α- proton is more deshielded. The cause of this has been described in the past and is supposed to be the conformation in which this atom is centered onto
|
||
<emphasis id="C5CF4546D138FFE0FD7EF94AFD79F943" bold="true" box="[743,758,1728,1747]" italics="true" pageId="3" pageNumber="4">N</emphasis>
|
||
4 (Gilbert, 1968). Otherwise, when these substituents are in the
|
||
<emphasis id="C5CF4546D138FFE0FD4CF956FC8DF97F" bold="true" box="[725,770,1756,1775]" italics="true" pageId="3" pageNumber="4">trans</emphasis>
|
||
position (3
|
||
<emphasis id="C5CF4546D138FFE0FF53F97DFF6DF89A" bold="true" box="[202,226,1783,1802]" italics="true" pageId="3" pageNumber="4">R*</emphasis>
|
||
,5
|
||
<emphasis id="C5CF4546D138FFE0FF6DF97DFE86F89A" bold="true" box="[244,265,1783,1802]" italics="true" pageId="3" pageNumber="4">S*</emphasis>
|
||
), the α- proton is more shielded, and it is found in the range of 3.90 to 3.65 ppm.
|
||
<figureCitation id="6F8085D1D138FFE0FEFBF899FE19F8B6" box="[354,406,1811,1830]" captionStart="Fig" captionStartId="4.[100,130,1146,1163]" captionTargetBox="[209,1379,148,1118]" captionTargetId="graphics-578@4.[209,1379,148,1118]" captionTargetPageId="4" captionText="Fig. 2. Indole alkaloids with a quebrachamine framework previously described in the literature employing at least 1H NMR analysis. The difference in the H-3 chemical shift of 3-epimers can be valuable for distinguishing between these diastereomers, which is highlighted. It must be mentioned that the C-3 configuration for all compounds shown was described to the contrary in Kutney’s article (Kutney et al., 1975). However, the correct configuration of these alkaloids had already been identified by Kompisˇet al. (1968)." figureDoi="http://doi.org/10.5281/zenodo.8240070" httpUri="https://zenodo.org/record/8240070/files/figure.png" pageId="3" pageNumber="4">Fig. 2</figureCitation>
|
||
shows this assumption in summary for
|
||
<emphasis id="C5CF4546D138FFE0FFFDF8A5FFFFF8D2" bold="true" box="[100,112,1839,1858]" pageId="3" pageNumber="4">1</emphasis>
|
||
and
|
||
<emphasis id="C5CF4546D138FFE0FF31F8A5FF3BF8D2" bold="true" box="[168,180,1839,1858]" pageId="3" pageNumber="4">2</emphasis>
|
||
supported by data of other known related 3-methyl esters. Accordingly, it was possible to elucidate the relative configuration at C-3 and C-5 of compounds
|
||
<emphasis id="C5CF4546D138FFE0FEA6F8EDFEC4F8EA" bold="true" box="[319,331,1895,1914]" pageId="3" pageNumber="4">1</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D138FFE0FEC1F8EDFEEBF8EA" bold="true" box="[344,356,1895,1914]" pageId="3" pageNumber="4">2</emphasis>
|
||
, and
|
||
<emphasis id="C5CF4546D138FFE0FE03F8EDFE29F8EA" bold="true" box="[410,422,1895,1914]" pageId="3" pageNumber="4">9</emphasis>
|
||
.
|
||
</paragraph>
|
||
<caption id="A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D" ID-Table-UUID="A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D" httpUri="http://table.plazi.org/id/A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D" pageId="3" pageNumber="4" startId="3.[100,150,150,166]" targetBox="[116,754,800,1480]" targetIsTable="true" targetPageId="3" targetType="table">
|
||
<paragraph id="F7049954D138FFE0FFFDFF1CFF28FF37" blockId="3.[100,770,150,269]" box="[100,167,150,167]" pageId="3" pageNumber="4">
|
||
<emphasis id="C5CF4546D138FFE0FFFDFF1CFF28FF37" bold="true" box="[100,167,150,167]" pageId="3" pageNumber="4">Table 1</emphasis>
|
||
</paragraph>
|
||
<paragraph id="F7049954D138FFE0FFFDFF3AFC8DFE9D" blockId="3.[100,770,150,269]" pageId="3" pageNumber="4">
|
||
Key correlations from 2D NMR experiments in the structure elucidation of undescribed alkaloid
|
||
<emphasis id="C5CF4546D138FFE0FEBDFF43FEA0FF4A" bold="true" box="[292,303,201,218]" pageId="3" pageNumber="4">9</emphasis>
|
||
(HMBC interaction – blue arrow; H2BC and COSY interaction – red bond) and its
|
||
<superScript id="00CE341CD138FFE0FEF5FF54FEFBFF7A" attach="right" box="[364,372,222,234]" fontSize="5" pageId="3" pageNumber="4">1</superScript>
|
||
H and
|
||
<superScript id="00CE341CD138FFE0FE34FF54FE32FF7A" attach="right" box="[429,445,222,234]" fontSize="5" pageId="3" pageNumber="4">13</superScript>
|
||
C NMR chemical shifts assigned to the related position in ppm with coupling constants (in parenthesis, reported in Hz)..
|
||
</paragraph>
|
||
</caption>
|
||
<paragraph id="F7049954D138FFE0FFEDFCAAFD19FA56" pageId="3" pageNumber="4">
|
||
<table id="85BB6BF4D138001CFFEDFCAAFD7DFA58" box="[116,754,800,1480]" gridcols="3" gridrows="29" pageId="3" pageNumber="4">
|
||
<tr id="498B9B16D138001CFFEDFCAAFD7DFCBE" box="[116,754,800,814]" gridrow="0" pageId="3" pageNumber="4" rowspan-2="1">
|
||
<th id="0A5AF26AD138001CFFEDFCAAFF4AFCBE" box="[116,197,800,814]" gridcol="0" gridrow="0" pageId="3" pageNumber="4">Position</th>
|
||
<th id="0A5AF26AD138001CFED3FCAAFE7FFCBE" box="[330,496,800,814]" gridcol="1" gridrow="0" pageId="3" pageNumber="4">vincaminorudeine 9</th>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFCC9FD7DFCC3" box="[116,754,835,851]" gridrow="1" pageId="3" pageNumber="4" rowspan-0="1">
|
||
<td id="0A5AF26AD138001CFED3FCC9FE7FFCC3" box="[330,496,835,851]" gridcol="1" gridrow="1" pageId="3" pageNumber="4">500 MHz, CDCl3</td>
|
||
<td id="0A5AF26AD138001CFDECFCC9FD7DFCC3" box="[629,754,835,851]" gridcol="2" gridrow="1" pageId="3" pageNumber="4">125 MHz, CDCl3</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFCECFD7DFCE4" box="[116,754,870,884]" gridrow="2" pageId="3" pageNumber="4" rowspan-1="1">
|
||
<th id="0A5AF26AD138001CFFEDFCECFF4AFCE4" box="[116,197,870,884]" gridcol="0" gridrow="2" pageId="3" pageNumber="4">2</th>
|
||
<td id="0A5AF26AD138001CFDECFCECFD7DFCE4" box="[629,754,870,884]" gridcol="2" gridrow="2" pageId="3" pageNumber="4">139.1</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFCF7FD7DFC1B" box="[116,754,893,907]" gridrow="3" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFCF7FF4AFC1B" box="[116,197,893,907]" gridcol="0" gridrow="3" pageId="3" pageNumber="4">3</th>
|
||
<td id="0A5AF26AD138001CFED3FCF7FE7FFC1B" box="[330,496,893,907]" gridcol="1" gridrow="3" pageId="3" pageNumber="4">4.39, dd (4.1, 2.7)</td>
|
||
<td id="0A5AF26AD138001CFDECFCF7FD7DFC1B" box="[629,754,893,907]" gridcol="2" gridrow="3" pageId="3" pageNumber="4">38.7</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFC19FD7DFC32" box="[116,754,915,930]" gridrow="4" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFC19FF4AFC32" box="[116,197,915,930]" gridcol="0" gridrow="4" pageId="3" pageNumber="4">4</th>
|
||
<td id="0A5AF26AD138001CFED3FC19FE7FFC32" box="[330,496,915,930]" gridcol="1" gridrow="4" pageId="3" pageNumber="4">2.63–2.55, m</td>
|
||
<td id="0A5AF26AD138001CFDECFC19FD7DFC32" box="[629,754,915,930]" gridcol="2" gridrow="4" pageId="3" pageNumber="4">31.1</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFC20FD7DFC29" box="[116,754,938,953]" gridrow="5" pageId="3" pageNumber="4" rowspan-0="1" rowspan-2="1">
|
||
<td id="0A5AF26AD138001CFED3FC20FE7FFC29" box="[330,496,938,953]" gridcol="1" gridrow="5" pageId="3" pageNumber="4">1.92, dd (14.3, 4.1)</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFC4BFD7DFC5F" box="[116,754,961,975]" gridrow="6" pageId="3" pageNumber="4" rowspan-1="1">
|
||
<th id="0A5AF26AD138001CFFEDFC4BFF4AFC5F" box="[116,197,961,975]" gridcol="0" gridrow="6" pageId="3" pageNumber="4">5</th>
|
||
<td id="0A5AF26AD138001CFDECFC4BFD7DFC5F" box="[629,754,961,975]" gridcol="2" gridrow="6" pageId="3" pageNumber="4">42.9</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFC52FD7DFC76" box="[116,754,984,998]" gridrow="7" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFC52FF4AFC76" box="[116,197,984,998]" gridcol="0" gridrow="7" pageId="3" pageNumber="4">6</th>
|
||
<td id="0A5AF26AD138001CFED3FC52FE7FFC76" box="[330,496,984,998]" gridcol="1" gridrow="7" pageId="3" pageNumber="4">1.36–1.21, m</td>
|
||
<td id="0A5AF26AD138001CFDECFC52FD7DFC76" box="[629,754,984,998]" gridcol="2" gridrow="7" pageId="3" pageNumber="4">31.7</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFC65FD7DFC6D" box="[116,754,1007,1021]" gridrow="8" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFC65FD7DFC6D" box="[116,754,1007,1021]" colspan="3" colspanRight="2" gridcol="0" gridrow="8" pageId="3" pageNumber="4">1.06, td (12.5, 5.5)</th>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFB8CFD7DFB84" box="[116,754,1030,1044]" gridrow="9" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFB8CFF4AFB84" box="[116,197,1030,1044]" gridcol="0" gridrow="9" pageId="3" pageNumber="4">7</th>
|
||
<td id="0A5AF26AD138001CFED3FB8CFE7FFB84" box="[330,496,1030,1044]" gridcol="1" gridrow="9" pageId="3" pageNumber="4">1.52–1.39, m</td>
|
||
<td id="0A5AF26AD138001CFDECFB8CFD7DFB84" box="[629,754,1030,1044]" gridcol="2" gridrow="9" pageId="3" pageNumber="4">22.3</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFB97FD7DFBBB" box="[116,754,1053,1067]" gridrow="10" pageId="3" pageNumber="4" rowspan-0="1" rowspan-2="1">
|
||
<td id="0A5AF26AD138001CFED3FB97FE7FFBBB" box="[330,496,1053,1067]" gridcol="1" gridrow="10" pageId="3" pageNumber="4">1.36–1.21, m</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFBB9FD7DFBD2" box="[116,754,1075,1090]" gridrow="11" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFBB9FF4AFBD2" box="[116,197,1075,1090]" gridcol="0" gridrow="11" pageId="3" pageNumber="4">8</th>
|
||
<td id="0A5AF26AD138001CFED3FBB9FE7FFBD2" box="[330,496,1075,1090]" gridcol="1" gridrow="11" pageId="3" pageNumber="4">2.38–2.22, m</td>
|
||
<td id="0A5AF26AD138001CFDECFBB9FD7DFBD2" box="[629,754,1075,1090]" gridcol="2" gridrow="11" pageId="3" pageNumber="4">55.2</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFBC0FD7DFBC9" box="[116,754,1098,1113]" gridrow="12" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFBC0FF4AFBC9" box="[116,197,1098,1113]" gridcol="0" gridrow="12" pageId="3" pageNumber="4">10</th>
|
||
<td id="0A5AF26AD138001CFED3FBC0FE7FFBC9" box="[330,496,1098,1113]" gridcol="1" gridrow="12" pageId="3" pageNumber="4">2.63–2.55, m</td>
|
||
<td id="0A5AF26AD138001CFDECFBC0FD7DFBC9" box="[629,754,1098,1113]" gridcol="2" gridrow="12" pageId="3" pageNumber="4">53.6</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFBEBFD7DFBE0" box="[116,754,1121,1136]" gridrow="13" pageId="3" pageNumber="4" rowspan-0="1" rowspan-2="1">
|
||
<td id="0A5AF26AD138001CFED3FBEBFE7FFBE0" box="[330,496,1121,1136]" gridcol="1" gridrow="13" pageId="3" pageNumber="4">2.38–2.22, m</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFBF2FD7DFB16" box="[116,754,1144,1158]" gridrow="14" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFBF2FF4AFB16" box="[116,197,1144,1158]" gridcol="0" gridrow="14" pageId="3" pageNumber="4">11</th>
|
||
<td id="0A5AF26AD138001CFED3FBF2FE7FFB16" box="[330,496,1144,1158]" gridcol="1" gridrow="14" pageId="3" pageNumber="4">3.05–2.85, m</td>
|
||
<td id="0A5AF26AD138001CFDECFBF2FD7DFB16" box="[629,754,1144,1158]" gridcol="2" gridrow="14" pageId="3" pageNumber="4">22.3</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFB05FD7DFB0D" box="[116,754,1167,1181]" gridrow="15" pageId="3" pageNumber="4" rowspan-1="1">
|
||
<th id="0A5AF26AD138001CFFEDFB05FF4AFB0D" box="[116,197,1167,1181]" gridcol="0" gridrow="15" pageId="3" pageNumber="4">12</th>
|
||
<td id="0A5AF26AD138001CFDECFB05FD7DFB0D" box="[629,754,1167,1181]" gridcol="2" gridrow="15" pageId="3" pageNumber="4">110.3</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFB2CFD7DFB24" box="[116,754,1190,1204]" gridrow="16" pageId="3" pageNumber="4" rowspan-1="1">
|
||
<th id="0A5AF26AD138001CFFEDFB2CFF4AFB24" box="[116,197,1190,1204]" gridcol="0" gridrow="16" pageId="3" pageNumber="4">13</th>
|
||
<td id="0A5AF26AD138001CFDECFB2CFD7DFB24" box="[629,754,1190,1204]" gridcol="2" gridrow="16" pageId="3" pageNumber="4">127.0</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFB37FD7DFB5B" box="[116,754,1213,1227]" gridrow="17" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFB37FF4AFB5B" box="[116,197,1213,1227]" gridcol="0" gridrow="17" pageId="3" pageNumber="4">14</th>
|
||
<td id="0A5AF26AD138001CFED3FB37FE7FFB5B" box="[330,496,1213,1227]" gridcol="1" gridrow="17" pageId="3" pageNumber="4">7.53, dd (7.8, 1.1)</td>
|
||
<td id="0A5AF26AD138001CFDECFB37FD7DFB5B" box="[629,754,1213,1227]" gridcol="2" gridrow="17" pageId="3" pageNumber="4">118.1</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFB59FD7DFB71" box="[116,754,1235,1249]" gridrow="18" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFB59FF4AFB71" box="[116,197,1235,1249]" gridcol="0" gridrow="18" pageId="3" pageNumber="4">15</th>
|
||
<td id="0A5AF26AD138001CFED3FB59FE7FFB71" box="[330,496,1235,1249]" gridcol="1" gridrow="18" pageId="3" pageNumber="4">7.09, dd (7.8, 1.1)</td>
|
||
<td id="0A5AF26AD138001CFDECFB59FD7DFB71" box="[629,754,1235,1249]" gridcol="2" gridrow="18" pageId="3" pageNumber="4">118.5</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFB60FD7DFB68" box="[116,754,1258,1272]" gridrow="19" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFB60FF4AFB68" box="[116,197,1258,1272]" gridcol="0" gridrow="19" pageId="3" pageNumber="4">16</th>
|
||
<td id="0A5AF26AD138001CFED3FB60FE7FFB68" box="[330,496,1258,1272]" gridcol="1" gridrow="19" pageId="3" pageNumber="4">7.19, dd (7.8, 1.1)</td>
|
||
<td id="0A5AF26AD138001CFDECFB60FD7DFB68" box="[629,754,1258,1272]" gridcol="2" gridrow="19" pageId="3" pageNumber="4">120.7</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFA8BFD7DFA9F" box="[116,754,1281,1295]" gridrow="20" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFA8BFF4AFA9F" box="[116,197,1281,1295]" gridcol="0" gridrow="20" pageId="3" pageNumber="4">17</th>
|
||
<td id="0A5AF26AD138001CFED3FA8BFE7FFA9F" box="[330,496,1281,1295]" gridcol="1" gridrow="20" pageId="3" pageNumber="4">7.27, dd (7.8, 1.1)</td>
|
||
<td id="0A5AF26AD138001CFDECFA8BFD7DFA9F" box="[629,754,1281,1295]" gridcol="2" gridrow="20" pageId="3" pageNumber="4">108.6</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFA92FD7DFAB6" box="[116,754,1304,1318]" gridrow="21" pageId="3" pageNumber="4" rowspan-1="1">
|
||
<th id="0A5AF26AD138001CFFEDFA92FF4AFAB6" box="[116,197,1304,1318]" gridcol="0" gridrow="21" pageId="3" pageNumber="4">18</th>
|
||
<td id="0A5AF26AD138001CFDECFA92FD7DFAB6" box="[629,754,1304,1318]" gridcol="2" gridrow="21" pageId="3" pageNumber="4">136.7</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFAA5FD7DFAAD" box="[116,754,1327,1341]" gridrow="22" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFAA5FF4AFAAD" box="[116,197,1327,1341]" gridcol="0" gridrow="22" pageId="3" pageNumber="4">19</th>
|
||
<td id="0A5AF26AD138001CFED3FAA5FE7FFAAD" box="[330,496,1327,1341]" gridcol="1" gridrow="22" pageId="3" pageNumber="4">3.75–3.70, m, overlap</td>
|
||
<td id="0A5AF26AD138001CFDECFAA5FD7DFAAD" box="[629,754,1327,1341]" gridcol="2" gridrow="22" pageId="3" pageNumber="4">56.6</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFACCFD7DFAC4" box="[116,754,1350,1364]" gridrow="23" pageId="3" pageNumber="4" rowspan-0="1" rowspan-2="1">
|
||
<td id="0A5AF26AD138001CFED3FACCFE7FFAC4" box="[330,496,1350,1364]" gridcol="1" gridrow="23" pageId="3" pageNumber="4">1.64, d (12.5)</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFAD6FD7DFAFB" box="[116,754,1372,1387]" gridrow="24" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFAD6FF4AFAFB" box="[116,197,1372,1387]" gridcol="0" gridrow="24" pageId="3" pageNumber="4">20</th>
|
||
<td id="0A5AF26AD138001CFED3FAD6FE7FFAFB" box="[330,496,1372,1387]" gridcol="1" gridrow="24" pageId="3" pageNumber="4">3.47, q (6.5)</td>
|
||
<td id="0A5AF26AD138001CFDECFAD6FD7DFAFB" box="[629,754,1372,1387]" gridcol="2" gridrow="24" pageId="3" pageNumber="4">74.2</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFAF9FD7DFA11" box="[116,754,1395,1409]" gridrow="25" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFAF9FF4AFA11" box="[116,197,1395,1409]" gridcol="0" gridrow="25" pageId="3" pageNumber="4">21</th>
|
||
<td id="0A5AF26AD138001CFED3FAF9FE7FFA11" box="[330,496,1395,1409]" gridcol="1" gridrow="25" pageId="3" pageNumber="4">1.29, d, overlap (6.5)</td>
|
||
<td id="0A5AF26AD138001CFDECFAF9FD7DFA11" box="[629,754,1395,1409]" gridcol="2" gridrow="25" pageId="3" pageNumber="4">17.6</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFA00FD7DFA08" box="[116,754,1418,1432]" gridrow="26" pageId="3" pageNumber="4" rowspan-1="1">
|
||
<th id="0A5AF26AD138001CFFEDFA00FF4AFA08" box="[116,197,1418,1432]" gridcol="0" gridrow="26" pageId="3" pageNumber="4">C= O</th>
|
||
<td id="0A5AF26AD138001CFDECFA00FD7DFA08" box="[629,754,1418,1432]" gridcol="2" gridrow="26" pageId="3" pageNumber="4">177.0</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFA2BFD7DFA22" box="[116,754,1441,1458]" gridrow="27" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFA2BFF4AFA22" box="[116,197,1441,1458]" gridcol="0" gridrow="27" pageId="3" pageNumber="4">3-COOCH3</th>
|
||
<td id="0A5AF26AD138001CFED3FA2BFE7FFA22" box="[330,496,1441,1458]" gridcol="1" gridrow="27" pageId="3" pageNumber="4">3.72, s, overlap</td>
|
||
<td id="0A5AF26AD138001CFDECFA2BFD7DFA22" box="[629,754,1441,1458]" gridcol="2" gridrow="27" pageId="3" pageNumber="4">52.7</td>
|
||
</tr>
|
||
<tr id="498B9B16D138001CFFEDFA32FD7DFA58" box="[116,754,1464,1480]" gridrow="28" pageId="3" pageNumber="4">
|
||
<th id="0A5AF26AD138001CFFEDFA32FF4AFA58" box="[116,197,1464,1480]" gridcol="0" gridrow="28" pageId="3" pageNumber="4">
|
||
<emphasis id="C5CF4546D138FFE0FFEDFA32FF0FFA56" bold="true" box="[116,128,1464,1478]" italics="true" pageId="3" pageNumber="4">N</emphasis>
|
||
CH3
|
||
</th>
|
||
<td id="0A5AF26AD138001CFED3FA32FE7FFA58" box="[330,496,1464,1480]" gridcol="1" gridrow="28" pageId="3" pageNumber="4">3.54, s</td>
|
||
<td id="0A5AF26AD138001CFDECFA32FD7DFA58" box="[629,754,1464,1480]" gridcol="2" gridrow="28" pageId="3" pageNumber="4">30.3</td>
|
||
</tr>
|
||
</table>
|
||
</paragraph>
|
||
<paragraph id="F7049954D138FFE0FF1DF809FBD4FE16" blockId="3.[100,771,1532,1970]" lastBlockId="3.[818,1488,147,1980]" pageId="3" pageNumber="4">
|
||
The NMR data of
|
||
<emphasis id="C5CF4546D138FFE0FEAAF809FEB0F806" bold="true" box="[307,319,1923,1942]" pageId="3" pageNumber="4">2</emphasis>
|
||
presented by Farahanikia et al. were different from our experimental findings (Farahanikia et al., 2011), which are summarized in
|
||
<tableCitation id="BA39ACEFD138FFE0FC51FF1EFB9EFF37" box="[968,1041,148,167]" captionStart="Table 2" captionStartId="5.[100,150,150,166]" captionTargetPageId="5" captionText="Table 2 Comparison of experimental NMR data of this work with those presented by Farahanikia et al. (2011) for the very same structure of vincaminoreine 2. The specific optical rotation was consistent with the published one by Farahanikia et al. (2011) and Mokrý et al. (1964). 1 H and 13C NMR chemical shifts are assigned to the related position in ppm with coupling constants for 1H NMR (in parenthesis, reported in Hz).." httpUri="http://table.plazi.org/id/A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64" pageId="3" pageNumber="4" tableUuid="A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64">Table 2</tableCitation>
|
||
. For instance, the chemical shift of α proton (H-3) was described as a multiplet at 1.96–1.93 ppm, but our experimental data, supported by 2D NMR experiments, confirmed the resonance of H-3 at 3.90 ppm, split into a doublet of doublets (
|
||
<emphasis id="C5CF4546D138FFE0FAD0FF62FADCFF6B" bold="true" box="[1353,1363,232,251]" italics="true" pageId="3" pageNumber="4">J</emphasis>
|
||
= 4.8 Hz and 2.9 Hz). In
|
||
<tableCitation id="BA39ACEFD138FFE0FC0EFE89FC53FE86" box="[919,988,259,278]" captionStart="Table 2" captionStartId="5.[100,150,150,166]" captionTargetPageId="5" captionText="Table 2 Comparison of experimental NMR data of this work with those presented by Farahanikia et al. (2011) for the very same structure of vincaminoreine 2. The specific optical rotation was consistent with the published one by Farahanikia et al. (2011) and Mokrý et al. (1964). 1 H and 13C NMR chemical shifts are assigned to the related position in ppm with coupling constants for 1H NMR (in parenthesis, reported in Hz).." httpUri="http://table.plazi.org/id/A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64" pageId="3" pageNumber="4" tableUuid="A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64">Table 2</tableCitation>
|
||
, our experimental
|
||
<superScript id="00CE341CD138FFE0FB13FF74FB1CFE9C" attach="right" box="[1162,1171,254,268]" fontSize="6" pageId="3" pageNumber="4">1</superScript>
|
||
H and
|
||
<superScript id="00CE341CD138FFE0FB57FF74FB6FFE9C" attach="right" box="[1230,1248,254,268]" fontSize="6" pageId="3" pageNumber="4">13</superScript>
|
||
C NMR chemical shifts for
|
||
<emphasis id="C5CF4546D138FFE0FCABFE95FCB1FEA2" bold="true" box="[818,830,287,306]" pageId="3" pageNumber="4">2</emphasis>
|
||
are compared with the previously published data. For further proof of this revision of the interpretation of the
|
||
<superScript id="00CE341CD138FFE0FB28FEBFFB35FED3" attach="right" box="[1201,1210,309,323]" fontSize="6" pageId="3" pageNumber="4">1</superScript>
|
||
H and
|
||
<superScript id="00CE341CD138FFE0FB63FEBFFA83FED3" attach="right" box="[1274,1292,309,323]" fontSize="6" pageId="3" pageNumber="4">13</superScript>
|
||
C spectra, a comparison of the chemical shifts of other 3-methyl ester quebrachamine derivatives was made (see
|
||
<figureCitation id="6F8085D1D138FFE0FB81FEF9FBC1FE16" box="[1048,1102,371,390]" captionStart="Fig" captionStartId="4.[100,130,1146,1163]" captionTargetBox="[209,1379,148,1118]" captionTargetId="graphics-578@4.[209,1379,148,1118]" captionTargetPageId="4" captionText="Fig. 2. Indole alkaloids with a quebrachamine framework previously described in the literature employing at least 1H NMR analysis. The difference in the H-3 chemical shift of 3-epimers can be valuable for distinguishing between these diastereomers, which is highlighted. It must be mentioned that the C-3 configuration for all compounds shown was described to the contrary in Kutney’s article (Kutney et al., 1975). However, the correct configuration of these alkaloids had already been identified by Kompisˇet al. (1968)." figureDoi="http://doi.org/10.5281/zenodo.8240070" httpUri="https://zenodo.org/record/8240070/files/figure.png" pageId="3" pageNumber="4">Fig. 2</figureCitation>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D138FFE0FCC8FE05FA92FE65" blockId="3.[818,1488,147,1980]" pageId="3" pageNumber="4">
|
||
For four isolated alkaloids, namely
|
||
<emphasis id="C5CF4546D138FFE0FB3AFE05FB20FE32" bold="true" box="[1187,1199,399,418]" pageId="3" pageNumber="4">5</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D138FFE0FB25FE05FB47FE32" bold="true" box="[1212,1224,399,418]" pageId="3" pageNumber="4">8</emphasis>
|
||
,
|
||
<emphasis id="C5CF4546D138FFE0FB4FFE05FB60FE32" bold="true" box="[1238,1263,399,418]" pageId="3" pageNumber="4">17</emphasis>
|
||
, and
|
||
<emphasis id="C5CF4546D138FFE0FABFFE05FAB0FE32" bold="true" box="[1318,1343,399,418]" pageId="3" pageNumber="4">23</emphasis>
|
||
, relevant NMR data have not yet been published. Therefore, all compounds were extensively analysed by NMR spectroscopy (1D, and 2D NMR experiments), HRMS, polarimetry, and circular dichroism.
|
||
</paragraph>
|
||
<paragraph id="F7049954D138FFE0FCC8FE74FC51FC08" blockId="3.[818,1488,147,1980]" pageId="3" pageNumber="4">
|
||
<materialsCitation id="47D39309D138FFE0FCC8FE74FC55FC08" collectionCode="N, MS, IR, UV, H, NMR" pageId="3" pageNumber="4" specimenCount="1">
|
||
Compounds
|
||
<emphasis id="C5CF4546D138FFE0FC5CFE74FC5EFD81" bold="true" box="[965,977,510,529]" pageId="3" pageNumber="4">5</emphasis>
|
||
and
|
||
<emphasis id="C5CF4546D138FFE0FC64FE74FB86FD81" bold="true" box="[1021,1033,510,529]" pageId="3" pageNumber="4">8</emphasis>
|
||
both belong to the aspidospermine
|
||
<typeStatus id="280027F6D138FFE0FAC9FE75FAF6FD82" box="[1360,1401,511,530]" pageId="3" pageNumber="4">type</typeStatus>
|
||
of indole alkaloids. Compound
|
||
<emphasis id="C5CF4546D138FFE0FC66FD90FB84FDBD" bold="true" box="[1023,1035,538,557]" pageId="3" pageNumber="4">5</emphasis>
|
||
was named as (±)-
|
||
<emphasis id="C5CF4546D138FFE0FB5DFD90FB5CFDBD" bold="true" box="[1220,1235,538,557]" italics="true" pageId="3" pageNumber="4">
|
||
<collectionCode id="91AA0191D138FFE0FB5DFD90FB5CFDBD" box="[1220,1235,538,557]" country="China" lsid="urn:lsid:biocol.org:col:13092" name="Nanjing University" pageId="3" pageNumber="4" type="Herbarium">N</collectionCode>
|
||
</emphasis>
|
||
-methylervinceine (its synthesis was reported in 1979) (Kuehne et al., 1979), and ()-2,3-anhydro-4-deacetoxy-6,7-dihydrovindoline, an intermediate in vindoline synthesis published in 1978 (Kutney et al., 1978). These articles provide
|
||
<collectionCode id="91AA0191D138FFE0FCABFD00FCDDFD0D" box="[818,850,650,669]" country="Italy" lsid="urn:lsid:biocol.org:col:14396" name="Herbarium Messanaensis, Università di Messina" pageId="3" pageNumber="4" type="Herbarium">MS</collectionCode>
|
||
,
|
||
<collectionCode id="91AA0191D138FFE0FCC3FD00FCFEFD0D" box="[858,881,650,669]" pageId="3" pageNumber="4">IR</collectionCode>
|
||
,
|
||
<collectionCode id="91AA0191D138FFE0FCE3FD00FC15FD0D" box="[890,922,650,669]" country="Colombia" name="Departamento de Biologia de la Universidad del Valle" pageId="3" pageNumber="4">UV</collectionCode>
|
||
, [
|
||
<emphasis id="C5CF4546D138FFE0FC35FD00FC38FD0D" bold="true" box="[940,951,650,669]" italics="true" pageId="3" pageNumber="4">a</emphasis>
|
||
]
|
||
<subScript id="6B3F9B11D138FFE0FC59FD1BFC44FD0F" attach="none" box="[960,971,657,671]" fontSize="6" pageId="3" pageNumber="4">D</subScript>
|
||
, and melting point, but only poor interpretations of the
|
||
<superScript id="00CE341CD138FFE0FCABFD2AFCB4FD3E" attach="right" box="[818,827,672,686]" fontSize="6" pageId="3" pageNumber="4">1</superScript>
|
||
<collectionCode id="91AA0191D138FFE0FCA2FD2CFCC4FD29" box="[827,843,678,697]" country="Finland" lsid="urn:lsid:biocol.org:col:15618" name="University of Helsinki" pageId="3" pageNumber="4" type="Herbarium">H</collectionCode>
|
||
<collectionCode id="91AA0191D138FFE0FCD6FD2CFCF0FD29" box="[847,895,678,697]" country="Netherlands" httpUri="http://grbio.org/cool/jyde-k516" name="Natuurhistorisch Museum" pageId="3" pageNumber="4">NMR</collectionCode>
|
||
spectrum. Kutney et al. (1978) described the optical rotation for the synthetic intermediate as [α]
|
||
<subScript id="6B3F9B11D138FFE0FBFFFD43FBFEFD47" attach="left" box="[1126,1137,713,727]" fontSize="6" pageId="3" pageNumber="4">D</subScript>
|
||
= 377.2 (c 0.17, CHCl
|
||
<subScript id="6B3F9B11D138FFE0FAC1FD43FAEEFD47" attach="left" box="[1368,1377,713,727]" fontSize="6" pageId="3" pageNumber="4">3</subScript>
|
||
). However, our experimental value was [α]
|
||
<subScript id="6B3F9B11D138FFE0FBFDFD6FFBE0FD63" attach="left" box="[1124,1135,741,755]" fontSize="6" pageId="3" pageNumber="4">D</subScript>
|
||
= 21.2 (c 0.17, CHCl
|
||
<subScript id="6B3F9B11D138FFE0FAC1FD6FFAEEFD63" attach="left" box="[1368,1377,741,755]" fontSize="6" pageId="3" pageNumber="4">3</subScript>
|
||
). Based on these facts, data of the isolated minovine (
|
||
<emphasis id="C5CF4546D138FFE0FB58FD73FB42FC9C" bold="true" box="[1217,1229,761,780]" pageId="3" pageNumber="4">4</emphasis>
|
||
), which is a well-described alkaloid (Ishikawa et al., 2006; Tan et al., 2016; Yuan et al., 2005), were used in comparison with its 16-methoxy analog (
|
||
<emphasis id="C5CF4546D138FFE0FA98FCBBFA98FCD4" bold="true" box="[1281,1303,817,836]" pageId="3" pageNumber="4">5)</emphasis>
|
||
. Experimental data were correlated with those of
|
||
<emphasis id="C5CF4546D138FFE0FBCAFCC7FBD0FCF0" bold="true" box="[1107,1119,845,864]" pageId="3" pageNumber="4">5</emphasis>
|
||
(see
|
||
<tableCitation id="BA39ACEFD138FFE0FB0AFCC7FB69FCF0" box="[1171,1254,845,864]" captionStart="Table 1" captionStartId="3.[100,150,150,166]" captionTargetPageId="3" captionText="Table 1 Key correlations from 2D NMR experiments in the structure elucidation of undescribed alkaloid 9 (HMBC interaction – blue arrow; H2BC and COSY interaction – red bond) and its 1H and 13C NMR chemical shifts assigned to the related position in ppm with coupling constants (in parenthesis, reported in Hz).." httpUri="http://table.plazi.org/id/A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D" pageId="3" pageNumber="4" tableUuid="A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D">Table S1</tableCitation>
|
||
); accordingly, the name 16-methoxyminovine fits much more properly for structure
|
||
<quantity id="304334B1D138FFE0FAE6FCE3FA28FCEC" box="[1407,1447,873,892]" metricMagnitude="-1" metricUnit="m" metricValue="1.27" pageId="3" pageNumber="4" unit="in" value="5.0">
|
||
<emphasis id="C5CF4546D138FFE0FAE6FCE3FA04FCEC" bold="true" box="[1407,1419,873,892]" pageId="3" pageNumber="4">5</emphasis>
|
||
in
|
||
</quantity>
|
||
the described context
|
||
</materialsCitation>
|
||
.
|
||
</paragraph>
|
||
<paragraph id="F7049954D138FFE0FCC8FC2BFBA5FA8F" blockId="3.[818,1488,147,1980]" pageId="3" pageNumber="4">
|
||
A similar issue occurred for
|
||
<emphasis id="C5CF4546D138FFE0FBF9FC2BFBE3FC24" bold="true" box="[1120,1132,929,948]" pageId="3" pageNumber="4">8</emphasis>
|
||
, with two names previously used for this compound. 16-Methoxyminovincine modified from 16-methoxyminovincinine by Oppenauer oxidation of the secondary hydroxyl, was previously described by melting point only, without analysis, but with determined stereochemistry (Doepke ¨and Meisel, 1968). The second name used for
|
||
<emphasis id="C5CF4546D138FFE0FC5CFBA6FC5EFBAF" bold="true" box="[965,977,1068,1087]" pageId="3" pageNumber="4">8</emphasis>
|
||
is minoriceine from the work of Zachystalova´et al. (1963), which was described as an isolated indole alkaloid from
|
||
<taxonomicName id="30BBE2D7D138FFE0FA05FBC2FCE9FBE7" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="3" pageNumber="4" phylum="Tracheophyta" rank="species" species="minor">
|
||
<emphasis id="C5CF4546D138FFE0FA05FBC2FCE9FBE7" bold="true" italics="true" pageId="3" pageNumber="4">Vinca minor</emphasis>
|
||
</taxonomicName>
|
||
L., with published analytical data for melting point, UV spectrum, and [
|
||
<emphasis id="C5CF4546D138FFE0FCFBFB0AFCE2FB03" bold="true" box="[866,877,1152,1171]" italics="true" pageId="3" pageNumber="4">a</emphasis>
|
||
]
|
||
<subScript id="6B3F9B11D138FFE0FCEFFB0DFC0EFB05" attach="none" box="[886,897,1159,1173]" fontSize="6" pageId="3" pageNumber="4">D</subScript>
|
||
. We believe that the compound presented under these names in the ’60s equals
|
||
<emphasis id="C5CF4546D138FFE0FC50FB16FC52FB3F" bold="true" box="[969,989,1180,1199]" pageId="3" pageNumber="4">8,</emphasis>
|
||
the 16-methoxy derivative of the well-known
|
||
<taxonomicName id="30BBE2D7D138FFE0FA05FB16FA40FB3F" box="[1436,1487,1180,1199]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="3" pageNumber="4" phylum="Tracheophyta" rank="genus">
|
||
<emphasis id="C5CF4546D138FFE0FA05FB16FA40FB3F" bold="true" box="[1436,1487,1180,1199]" italics="true" pageId="3" pageNumber="4">Vinca</emphasis>
|
||
</taxonomicName>
|
||
alkaloid minovincine (
|
||
<emphasis id="C5CF4546D138FFE0FB92FB32FB98FB5B" bold="true" box="[1035,1047,1208,1227]" pageId="3" pageNumber="4">7</emphasis>
|
||
), also isolated in our work. According to the comparison of the 1D and 2D NMR data, and the similar optical rotation value of
|
||
<emphasis id="C5CF4546D138FFE0FC1AFB65FC00FA92" bold="true" box="[899,911,1263,1282]" pageId="3" pageNumber="4">8</emphasis>
|
||
with its analog
|
||
<emphasis id="C5CF4546D138FFE0FBBEFB7AFBBCFA93" bold="true" box="[1063,1075,1264,1283]" pageId="3" pageNumber="4">7</emphasis>
|
||
(see
|
||
<tableCitation id="BA39ACEFD138FFE0FBFCFB7AFB39FA93" box="[1125,1206,1264,1283]" captionStart="Table 2" captionStartId="5.[100,150,150,166]" captionTargetPageId="5" captionText="Table 2 Comparison of experimental NMR data of this work with those presented by Farahanikia et al. (2011) for the very same structure of vincaminoreine 2. The specific optical rotation was consistent with the published one by Farahanikia et al. (2011) and Mokrý et al. (1964). 1 H and 13C NMR chemical shifts are assigned to the related position in ppm with coupling constants for 1H NMR (in parenthesis, reported in Hz).." httpUri="http://table.plazi.org/id/A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64" pageId="3" pageNumber="4" tableUuid="A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64">Table S2</tableCitation>
|
||
), the name 16-methoxyminovincine has been set for
|
||
<emphasis id="C5CF4546D138FFE0FB8EFA81FBACFA8E" bold="true" box="[1047,1059,1291,1310]" pageId="3" pageNumber="4">8</emphasis>
|
||
.
|
||
</paragraph>
|
||
<paragraph id="F7049954D138FFE0FCC8FAADFB93F830" blockId="3.[818,1488,147,1980]" pageId="3" pageNumber="4">
|
||
After 2D NMR confirmation of the unusual picraline
|
||
<typeStatus id="280027F6D138FFE0FAD2FAA2FAFBFAAB" box="[1355,1396,1320,1339]" pageId="3" pageNumber="4">type</typeStatus>
|
||
alkaloids raucubainine (
|
||
<emphasis id="C5CF4546D138FFE0FC23FAC9FC5CFAC6" bold="true" box="[954,979,1347,1366]" pageId="3" pageNumber="4">17</emphasis>
|
||
) and raucubaine (
|
||
<emphasis id="C5CF4546D138FFE0FBE6FAC9FB17FAC6" bold="true" box="[1151,1176,1347,1366]" pageId="3" pageNumber="4">23</emphasis>
|
||
), only interpretations of
|
||
<superScript id="00CE341CD138FFE0FA18FAB7FA05FADB" attach="right" box="[1409,1418,1341,1355]" fontSize="6" pageId="3" pageNumber="4">1</superScript>
|
||
H NMR spectra were found in the literature as references. The identified chemical constitution of
|
||
<emphasis id="C5CF4546D138FFE0FBB9FAF1FBB6FA1E" bold="true" box="[1056,1081,1403,1422]" pageId="3" pageNumber="4">17</emphasis>
|
||
with an epoxide moiety was found in the structure of raucubainine (
|
||
<taxonomicName id="30BBE2D7D138FFE0FBA3FA1DFACFFA3A" authority="Griseb." authorityName="Griseb." box="[1082,1344,1431,1450]" class="Magnoliopsida" family="Apocynaceae" genus="Rauvolfia" kingdom="Plantae" order="Gentianales" pageId="3" pageNumber="4" phylum="Tracheophyta" rank="species" species="salicifolia">
|
||
<emphasis id="C5CF4546D138FFE0FBA3FA1DFB60FA3A" bold="true" box="[1082,1263,1431,1450]" italics="true" pageId="3" pageNumber="4">Rauvolfia salicifolia</emphasis>
|
||
Griseb.
|
||
</taxonomicName>
|
||
, (Sierra et al., 1982)) and quaternoxine (
|
||
<taxonomicName id="30BBE2D7D138FFE0FBB3FA38FA42FA56" authority="Van Heurck & Mull. Arg." authorityName="Van Heurck & Mull. Arg." box="[1066,1485,1458,1478]" class="Magnoliopsida" family="Apocynaceae" genus="Alstonia" kingdom="Plantae" order="Gentianales" pageId="3" pageNumber="4" phylum="Tracheophyta" rank="species" species="quaternata">
|
||
<emphasis id="C5CF4546D138FFE0FBB3FA38FB55FA56" bold="true" box="[1066,1242,1458,1478]" italics="true" pageId="3" pageNumber="4">Alstonia quaternata</emphasis>
|
||
Van Heurck & Müll. Arg.
|
||
</taxonomicName>
|
||
, (Mamatas-Kalamaras et al., 1975)), previously described diastereomers. The assignment of individual
|
||
<collectingCountry id="8FACD9C4D138FFE0FBC1FA61FBFAFA6E" box="[1112,1141,1515,1534]" name="Switzerland" pageId="3" pageNumber="4">CH</collectingCountry>
|
||
<subScript id="6B3F9B11D138FFE0FBECFA78FBF1F990" attach="left" box="[1141,1150,1522,1536]" fontSize="6" pageId="3" pageNumber="4">3</subScript>
|
||
/
|
||
<collectingCountry id="8FACD9C4D138FFE0FB1FFA61FB29FA6E" box="[1158,1190,1515,1534]" name="Switzerland" pageId="3" pageNumber="4">CH</collectingCountry>
|
||
<subScript id="6B3F9B11D138FFE0FB3FFA78FB20F990" attach="left" box="[1190,1199,1522,1536]" fontSize="6" pageId="3" pageNumber="4">2</subScript>
|
||
/
|
||
<collectingCountry id="8FACD9C4D138FFE0FB2FFA61FB58FA6E" box="[1206,1239,1515,1534]" name="Switzerland" pageId="3" pageNumber="4">CH</collectingCountry>
|
||
/C groups in the original article (Sierra et al., 1982) has been revised (see
|
||
<tableCitation id="BA39ACEFD138FFE0FB6DF98CFACAF98A" box="[1268,1349,1542,1562]" captionStart="Table 3" captionStartId="6.[100,150,1013,1029]" captionTargetPageId="6" captionText="Table 3 Biological activities of isolated Vinca minor alkaloids." httpUri="http://table.plazi.org/id/A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" pageId="3" pageNumber="4" tableUuid="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F">Table S3</tableCitation>
|
||
). Based on our analysis of the 2D NMR spectra, the interchange of methylene groups at positions 6 and 14 was recognized in comparison with the previous assignment. The red-colored bonds in
|
||
<figureCitation id="6F8085D1D138FFE0FB00F9D0FB41F9FD" box="[1177,1230,1626,1645]" captionStart="Fig" captionStartId="6.[100,130,596,613]" captionTargetBox="[106,764,148,568]" captionTargetId="graphics-420@6.[106,730,189,483]" captionTargetPageId="6" captionText="Fig. 3. Described key 2D NMR correlations of revision of previously assigned positions in molecule 17 (COSY interaction – red bond, HMBC interaction – blue arrow). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)" figureDoi="http://doi.org/10.5281/zenodo.8240072" httpUri="https://zenodo.org/record/8240072/files/figure.png" pageId="3" pageNumber="4">Fig. 3</figureCitation>
|
||
show COSY correlations of 3.83 (H-5)/1.69 ppm (H-6) and 3.83 (H-5)/2.72–2.68 ppm (H-6), determining the ethylene connection from the indoline moiety to the second tertiary nitrogen. In addition, the spin-spin system H-2/H-3/H-14/H-15/H-16 was also confirmed in the COSY experiment. Another proof is HMBC correlations of H-6 to the quaternary sp
|
||
<superScript id="00CE341CD138FFE0FA19F96AFA06F97E" attach="left" box="[1408,1417,1760,1774]" fontSize="6" pageId="3" pageNumber="4">2</superScript>
|
||
carbon C-8, as well as correlations over three bonds of methylene H-14 to C-2, C-16, and C-20 (see
|
||
<figureCitation id="6F8085D1D138FFE0FC73F897FB91F8A1" box="[1002,1054,1821,1841]" captionStart="Fig" captionStartId="6.[100,130,596,613]" captionTargetBox="[106,764,148,568]" captionTargetId="graphics-420@6.[106,730,189,483]" captionTargetPageId="6" captionText="Fig. 3. Described key 2D NMR correlations of revision of previously assigned positions in molecule 17 (COSY interaction – red bond, HMBC interaction – blue arrow). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)" figureDoi="http://doi.org/10.5281/zenodo.8240072" httpUri="https://zenodo.org/record/8240072/files/figure.png" pageId="3" pageNumber="4">Fig. 3</figureCitation>
|
||
). The results of the NOESY experiment suggest two possible orientations of the epoxide to the rest of the molecule, which was impossible to distinguish without X-ray analysis. Therefore, the configuration at C-19 and C-20 remains undetermined, as in the case with Sierra et al. (1982).
|
||
</paragraph>
|
||
<paragraph id="F7049954D138FFE7FCC8F823FDF8F90A" blockId="3.[818,1488,147,1980]" lastBlockId="4.[100,770,1280,1690]" lastPageId="4" lastPageNumber="5" pageId="3" pageNumber="4">
|
||
Two diastereomers, raucubaine (Sierra et al., 1982) and quaternoline (Mamatas-Kalamaras et al., 1975), are described for the constitution of
|
||
<emphasis id="C5CF4546D13FFFE7FFFDFA96FFF2FABF" bold="true" box="[100,125,1308,1327]" pageId="4" pageNumber="5">23</emphasis>
|
||
as well. Quaternoline was excluded from the comparison due to its poorly described analytical data, as was the case with quaternoxine and alkaloid
|
||
<emphasis id="C5CF4546D13FFFE7FF20FADEFF5DFAF7" bold="true" box="[185,210,1364,1383]" pageId="4" pageNumber="5">17</emphasis>
|
||
. Nevertheless, the
|
||
<superScript id="00CE341CD13FFFE7FE14FAC4FE19FACC" attach="right" box="[397,406,1358,1372]" fontSize="6" pageId="4" pageNumber="5">1</superScript>
|
||
H NMR spectrum presented by Sierra et al. (1982) corresponds to our experimental data perfectly, along with specific optical rotation and circular dichroism data. The configuration of raucubaine was previously determined by X-ray (Pauptit and Trotter, 1981), CD analysis, and polarimetry (Sierra et al., 1982) in one collaboration. When comparing the experimental
|
||
<superScript id="00CE341CD13FFFE7FD8DFA50FD92FA78" attach="right" box="[532,541,1498,1512]" fontSize="6" pageId="4" pageNumber="5">1</superScript>
|
||
H NMR spectral details with those published for raucubaine (Sierra et al., 1982), almost identical chemical shifts were observed (see Table S4). The missing
|
||
<superScript id="00CE341CD13FFFE7FD37F998FD4FF9B0" attach="right" box="[686,704,1554,1568]" fontSize="6" pageId="4" pageNumber="5">13</superScript>
|
||
C NMR spectrum interpretation of
|
||
<emphasis id="C5CF4546D13FFFE7FEFCF9B9FEF1F9D6" bold="true" box="[357,382,1587,1606]" pageId="4" pageNumber="5">23</emphasis>
|
||
, with established stereochemistry of 2
|
||
<emphasis id="C5CF4546D13FFFE7FD77F9B9FD73F9D6" bold="true" box="[750,764,1587,1606]" italics="true" pageId="4" pageNumber="5">R</emphasis>
|
||
, 3
|
||
<emphasis id="C5CF4546D13FFFE7FFE9F9C5FFF4F9F2" bold="true" box="[112,123,1615,1634]" italics="true" pageId="4" pageNumber="5">S</emphasis>
|
||
,7
|
||
<emphasis id="C5CF4546D13FFFE7FF14F9C5FF14F9F2" bold="true" box="[141,155,1615,1634]" italics="true" pageId="4" pageNumber="5">R</emphasis>
|
||
,15
|
||
<emphasis id="C5CF4546D13FFFE7FF20F9C5FF48F9F2" bold="true" box="[185,199,1615,1634]" italics="true" pageId="4" pageNumber="5">R</emphasis>
|
||
,16
|
||
<emphasis id="C5CF4546D13FFFE7FF7DF9C5FF7DF9F2" bold="true" box="[228,242,1615,1634]" italics="true" pageId="4" pageNumber="5">R</emphasis>
|
||
,19
|
||
<emphasis id="C5CF4546D13FFFE7FE89F9C5FE91F9F2" bold="true" box="[272,286,1615,1634]" italics="true" pageId="4" pageNumber="5">R</emphasis>
|
||
,20
|
||
<emphasis id="C5CF4546D13FFFE7FEA2F9C5FEC9F9F2" bold="true" box="[315,326,1615,1634]" italics="true" pageId="4" pageNumber="5">S</emphasis>
|
||
, is presented in the Supplementary Data, together with the data of other isolated known alkaloids for which the NMR spectroscopic details have not been fully reported.
|
||
</paragraph>
|
||
</subSubSection>
|
||
<caption id="A3C4C9DCD13FFFE7FFFDFBF0FE03FB47" ID-DOI="http://doi.org/10.5281/zenodo.8240070" ID-Zenodo-Dep="8240070" httpUri="https://zenodo.org/record/8240070/files/figure.png" pageId="4" pageNumber="5" startId="4.[100,130,1146,1163]" targetBox="[209,1379,148,1118]" targetPageId="4" targetType="figure">
|
||
<paragraph id="F7049954D13FFFE7FFFDFBF0FE03FB47" blockId="4.[100,1487,1141,1239]" pageId="4" pageNumber="5">
|
||
<emphasis id="C5CF4546D13FFFE7FFFDFBF0FF10FB1B" bold="true" box="[100,159,1146,1163]" pageId="4" pageNumber="5">Fig. 2.</emphasis>
|
||
Indole alkaloids with a quebrachamine framework previously described in the literature employing at least
|
||
<superScript id="00CE341CD13FFFE7FBCAFBFFFBD4FB11" attach="right" box="[1107,1115,1141,1153]" fontSize="5" pageId="4" pageNumber="5">1</superScript>
|
||
H NMR analysis. The difference in the H-3 chemical shift of 3-epimers can be valuable for distinguishing between these diastereomers, which is highlighted. It must be mentioned that the C-3 configuration for all compounds shown was described to the contrary in Kutney’ s article (Kutney et al., 1975). However, the correct configuration of these alkaloids had already been identified by Kompisˇet al. (1968).
|
||
</paragraph>
|
||
</caption>
|
||
<subSubSection id="BFA1CADFD13FFFE5FFFDF941FC68FEFA" lastPageId="6" lastPageNumber="7" pageId="4" pageNumber="5" type="biology_ecology">
|
||
<paragraph id="F7049954D13FFFE7FFFDF941FDA4F94E" blockId="4.[100,555,1739,1758]" box="[100,555,1739,1758]" pageId="4" pageNumber="5">
|
||
<heading id="AC4C2E38D13FFFE7FFFDF941FDA4F94E" bold="true" box="[100,555,1739,1758]" fontSize="36" level="1" pageId="4" pageNumber="5" reason="1">
|
||
<emphasis id="C5CF4546D13FFFE7FFFDF941FDA4F94E" bold="true" box="[100,555,1739,1758]" italics="true" pageId="4" pageNumber="5">2.2. Biological activity of isolated indole alkaloids</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13FFFE7FF1DF889FAD9F805" blockId="4.[100,770,1795,1984]" lastBlockId="4.[818,1488,1280,1969]" pageId="4" pageNumber="5">
|
||
All the isolated alkaloids were tested for their inhibition of
|
||
<emphasis id="C5CF4546D13FFFE7FD5BF889FD42F886" bold="true" box="[706,717,1795,1814]" italics="true" pageId="4" pageNumber="5">h</emphasis>
|
||
AChE and
|
||
<emphasis id="C5CF4546D13FFFE7FF17F895FF16F8A2" bold="true" box="[142,153,1823,1842]" italics="true" pageId="4" pageNumber="5">h</emphasis>
|
||
BuChE. Alkaloids obtained in sufficient amounts were also evaluated for their activity against POP. To determine
|
||
<emphasis id="C5CF4546D13FFFE7FDDCF8B1FDDFF8DE" bold="true" box="[581,592,1851,1870]" italics="true" pageId="4" pageNumber="5">h</emphasis>
|
||
AChE and
|
||
<emphasis id="C5CF4546D13FFFE7FD21F8B1FD4CF8DE" bold="true" box="[696,707,1851,1870]" italics="true" pageId="4" pageNumber="5">h</emphasis>
|
||
BuChE inhibition properties, galanthamine and eserine were used as reference compounds. Regarding the POP inhibition assay, berberine served as a reference compound. Results of the biological studies are summarized in
|
||
<tableCitation id="BA39ACEFD13FFFE7FFFDF821FF25F82E" box="[100,170,1963,1982]" captionStart="Table 3" captionStartId="6.[100,150,1013,1029]" captionTargetPageId="6" captionText="Table 3 Biological activities of isolated Vinca minor alkaloids." httpUri="http://table.plazi.org/id/A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" pageId="4" pageNumber="5" tableUuid="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F">Table 3</tableCitation>
|
||
. In the
|
||
<emphasis id="C5CF4546D13FFFE7FF6BF820FF72F82D" bold="true" box="[242,253,1962,1981]" italics="true" pageId="4" pageNumber="5">h</emphasis>
|
||
AChE assay, all isolated alkaloids were inactive (IC
|
||
<subScript id="6B3F9B11D13FFFE7FD43F838FD63F850" attach="left" box="[730,748,1970,1984]" fontSize="6" pageId="4" pageNumber="5">50</subScript>
|
||
<emphasis id="C5CF4546D13FFFE7FD68F821FC8EF82E" box="[753,769,1963,1982]" italics="true" pageId="4" pageNumber="5">></emphasis>
|
||
100 μM,
|
||
<tableCitation id="BA39ACEFD13FFFE7FC11FA8AFC5FFA84" box="[904,976,1280,1300]" captionStart="Table 3" captionStartId="6.[100,150,1013,1029]" captionTargetPageId="6" captionText="Table 3 Biological activities of isolated Vinca minor alkaloids." httpUri="http://table.plazi.org/id/A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" pageId="4" pageNumber="5" tableUuid="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F">Table 3</tableCitation>
|
||
). On the other hand, some of the alkaloids showed a promising capacity to inhibit
|
||
<emphasis id="C5CF4546D13FFFE7FBD8FA96FBC3FABF" bold="true" box="[1089,1100,1308,1327]" italics="true" pageId="4" pageNumber="5">h</emphasis>
|
||
BuChE. Vincaminoreine (
|
||
<emphasis id="C5CF4546D13FFFE7FAAEFA96FACCFABF" bold="true" box="[1335,1347,1308,1327]" pageId="4" pageNumber="5">2</emphasis>
|
||
) and vincorine (
|
||
<emphasis id="C5CF4546D13FFFE7FCA3FAB2FCDCFADB" bold="true" box="[826,851,1336,1355]" pageId="4" pageNumber="5">11</emphasis>
|
||
) demonstrated inhibition potential in the single-digit micromolar range with IC
|
||
<subScript id="6B3F9B11D13FFFE7FC20FAD1FC44FAF9" attach="left" box="[953,971,1371,1385]" fontSize="6" pageId="4" pageNumber="5">50</subScript>
|
||
values of = 8.71 ± 0.49 μM, and 9.75 ± 0.45 μM, respectively. The best
|
||
<emphasis id="C5CF4546D13FFFE7FB9CFAFAFB9FFA13" bold="true" box="[1029,1040,1392,1411]" italics="true" pageId="4" pageNumber="5">h</emphasis>
|
||
BuChE inhibition activity was demonstrated by ()-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1
|
||
<emphasis id="C5CF4546D13FFFE7FB4CFA06FB6BFA0F" bold="true" box="[1237,1252,1420,1439]" italics="true" pageId="4" pageNumber="5">H</emphasis>
|
||
-indole (also known as demethoxycarbonyltetrahydrosecodine (Aclinou et al., 1994),
|
||
<emphasis id="C5CF4546D13FFFE7FAE4FA22FA19FA2B" bold="true" box="[1405,1430,1448,1467]" pageId="4" pageNumber="5">19</emphasis>
|
||
) with an IC
|
||
<subScript id="6B3F9B11D13FFFE7FCFDFA41FCF9FA49" attach="left" box="[868,886,1483,1497]" fontSize="6" pageId="4" pageNumber="5">50</subScript>
|
||
value of 650 ± 16 nM. This structurally simple indole alkaloid has been previously isolated from other
|
||
<taxonomicName id="30BBE2D7D13FFFE7FB4AFA6AFAC1FA63" box="[1235,1358,1504,1523]" class="Magnoliopsida" family="Apocynaceae" kingdom="Plantae" order="Gentianales" pageId="4" pageNumber="5" phylum="Tracheophyta" rank="family">Apocynaceae</taxonomicName>
|
||
plants (e.g.,
|
||
<taxonomicName id="30BBE2D7D13FFFE7FCABFA71FBF3F99F" authority="L. D. Benson" authorityName="L. D. Benson" box="[818,1148,1531,1551]" class="Magnoliopsida" family="Apocynaceae" genus="Haplophyton" kingdom="Plantae" order="Gentianales" pageId="4" pageNumber="5" phylum="Tracheophyta" rank="species" species="crooksii">
|
||
<emphasis id="C5CF4546D13FFFE7FCABFA71FC7CF99E" bold="true" box="[818,1011,1531,1550]" italics="true" pageId="4" pageNumber="5">Haplophyton crooksii</emphasis>
|
||
L. D. Benson
|
||
</taxonomicName>
|
||
, and
|
||
<taxonomicName id="30BBE2D7D13FFFE7FB2FFA71FCEBF9BA" authority="Stapf" authorityName="Stapf" class="Magnoliopsida" family="Apocynaceae" genus="Tabernaemontana" kingdom="Plantae" order="Gentianales" pageId="4" pageNumber="5" phylum="Tracheophyta" rank="species" species="pachysiphon">
|
||
<emphasis id="C5CF4546D13FFFE7FB2FFA71FA40F99E" bold="true" box="[1206,1487,1531,1550]" italics="true" pageId="4" pageNumber="5">Tabernaemontana pachysiphon</emphasis>
|
||
Stapf
|
||
</taxonomicName>
|
||
) and tested for its potential to inhibit AChE from electric eel (Crooks et al., 1968; Mroue et al., 1996). The obtained inhibition potency within the previous study (IC
|
||
<subScript id="6B3F9B11D13FFFE7FB1AF9DCFB1AF9F4" attach="left" box="[1155,1173,1622,1636]" fontSize="6" pageId="4" pageNumber="5">50</subScript>
|
||
= 203 μM) is in agreement with our results (IC
|
||
<subScript id="6B3F9B11D13FFFE7FC25F9F8FC41F910" attach="left" box="[956,974,1650,1664]" fontSize="6" pageId="4" pageNumber="5">50</subScript>
|
||
=
|
||
<emphasis id="C5CF4546D13FFFE7FC77F9E1FC71F9EE" box="[1006,1022,1643,1662]" italics="true" pageId="4" pageNumber="5">></emphasis>
|
||
100 μM;
|
||
<tableCitation id="BA39ACEFD13FFFE7FBC6F9E1FB27F9EE" box="[1119,1192,1643,1662]" captionStart="Table 3" captionStartId="6.[100,150,1013,1029]" captionTargetPageId="6" captionText="Table 3 Biological activities of isolated Vinca minor alkaloids." httpUri="http://table.plazi.org/id/A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" pageId="4" pageNumber="5" tableUuid="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F">Table 3</tableCitation>
|
||
), pointing to very weak AChE inhibition potency. Compound (+)-
|
||
<emphasis id="C5CF4546D13FFFE7FB1AF90DFB13F90A" bold="true" box="[1155,1180,1671,1690]" pageId="4" pageNumber="5">19</emphasis>
|
||
was isolated from the leaves of
|
||
<taxonomicName id="30BBE2D7D13FFFE7FCABF928FA80F926" authority="Decne. (Ur-Rahman et al., 1991 b)" box="[818,1295,1698,1718]" class="Magnoliopsida" family="Apocynaceae" genus="Rhazya" kingdom="Plantae" order="Gentianales" pageId="4" pageNumber="5" phylum="Tracheophyta" rank="species" species="stricta">
|
||
<emphasis id="C5CF4546D13FFFE7FCABF928FC39F926" bold="true" box="[818,950,1698,1718]" italics="true" pageId="4" pageNumber="5">Rhazya stricta</emphasis>
|
||
Decne. (Ur-Rahman et al., 1991b)
|
||
</taxonomicName>
|
||
. The cholinesterase inhibition activity of the (+)-isomer has not been studied. Since these alkaloids are isolated from natural sources only in a limited amount, the possibility of stereoselective synthesis of the (+)-isomer was successfully explored by Palmisano et al. (1995). Both isomers can also be synthetically prepared with a shorter route by alkylation of phenylglycinol-derived bicyclic lactams (Amat et al., 2005). The preparation of semisynthetic analogues derived from
|
||
<emphasis id="C5CF4546D13FFFE7FB61F8ECFA9EF8E9" bold="true" box="[1272,1297,1894,1913]" pageId="4" pageNumber="5">19</emphasis>
|
||
could be interesting for the further development of selective BuChE inhibitors.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13FFFE6FCC8F814FE41F92F" blockId="4.[818,1488,1280,1969]" lastBlockId="5.[100,771,1624,1979]" lastPageId="5" lastPageNumber="6" pageId="4" pageNumber="5">
|
||
For POP inhibition potency, alkaloid
|
||
<emphasis id="C5CF4546D13FFFE7FB4EF814FB7FF821" bold="true" box="[1239,1264,1950,1969]" pageId="4" pageNumber="5">19</emphasis>
|
||
was the most active compound in our study. Compound
|
||
<emphasis id="C5CF4546D13EFFE6FE53F9D2FE6CF9FB" bold="true" box="[458,483,1624,1643]" pageId="5" pageNumber="6">19</emphasis>
|
||
revealed two-digit inhibition ability, with an IC
|
||
<subScript id="6B3F9B11D13EFFE6FE95F9F1FE91F919" attach="left" box="[268,286,1659,1673]" fontSize="6" pageId="5" pageNumber="6">50</subScript>
|
||
value of 58 ± 0.45 μM (
|
||
<tableCitation id="BA39ACEFD13EFFE6FE66F9FEFDCAF917" box="[511,581,1652,1671]" captionStart="Table 3" captionStartId="6.[100,150,1013,1029]" captionTargetPageId="6" captionText="Table 3 Biological activities of isolated Vinca minor alkaloids." httpUri="http://table.plazi.org/id/A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" pageId="5" pageNumber="6" tableUuid="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F">Table 3</tableCitation>
|
||
), being nearly three times more active than berberine, an isoquinoline alkaloid recognized as a POP inhibitor (Tarrago et al., 2007).
|
||
</paragraph>
|
||
<caption id="A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64" ID-Table-UUID="A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64" httpUri="http://table.plazi.org/id/A3C4C9DCD13EFFE6FFFDFF1CFCCFFF64" pageId="5" pageNumber="6" startId="5.[100,150,150,166]" targetBox="[116,1345,777,1570]" targetIsTable="true" targetPageId="5" targetType="table">
|
||
<paragraph id="F7049954D13EFFE6FFFDFF1CFF28FF37" blockId="5.[100,1487,150,244]" box="[100,167,150,167]" pageId="5" pageNumber="6">
|
||
<emphasis id="C5CF4546D13EFFE6FFFDFF1CFF28FF37" bold="true" box="[100,167,150,167]" pageId="5" pageNumber="6">Table 2</emphasis>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13EFFE6FFFDFF3AFCCFFF64" blockId="5.[100,1487,150,244]" pageId="5" pageNumber="6">
|
||
Comparison of experimental NMR data of this work with those presented by Farahanikia et al. (2011) for the very same structure of vincaminoreine
|
||
<emphasis id="C5CF4546D13EFFE6FACDFF3AFAD0FF51" bold="true" box="[1364,1375,176,193]" pageId="5" pageNumber="6">2</emphasis>
|
||
. The specific optical rotation was consistent with the published one by Farahanikia et al. (2011) and Mokrý et al. (1964).
|
||
<superScript id="00CE341CD13EFFE6FC7FFF4EFC61FF40" attach="right" box="[998,1006,196,208]" fontSize="5" pageId="5" pageNumber="6">1</superScript>
|
||
H and
|
||
<superScript id="00CE341CD13EFFE6FBBDFF4EFBBBFF40" attach="right" box="[1060,1076,196,208]" fontSize="5" pageId="5" pageNumber="6">13</superScript>
|
||
C NMR chemical shifts are assigned to the related position in ppm with coupling constants for
|
||
<superScript id="00CE341CD13EFFE6FE44FF54FE6AFF7A" attach="right" box="[477,485,222,234]" fontSize="5" pageId="5" pageNumber="6">1</superScript>
|
||
H NMR (in parenthesis, reported in Hz)..
|
||
</paragraph>
|
||
</caption>
|
||
<paragraph id="F7049954D13EFFE6FFEDFC83FA8FF9B2" pageId="5" pageNumber="6">
|
||
<table id="85BB6BF4D13E001CFFEDFC83FACEF9B2" box="[116,1345,777,1570]" gridcols="5" gridrows="34" pageId="5" pageNumber="6">
|
||
<tr id="498B9B16D13E001CFFEDFC83FACEFC88" box="[116,1345,777,792]" gridrow="0" pageId="5" pageNumber="6" rowspan-2="1">
|
||
<th id="0A5AF26AD13E001CFFEDFC83FF4AFC88" box="[116,197,777,792]" gridcol="0" gridrow="0" pageId="5" pageNumber="6">Position</th>
|
||
<th id="0A5AF26AD13E001CFEF8FC83FDC0FC88" box="[353,591,777,792]" gridcol="1" gridrow="0" pageId="5" pageNumber="6">Experimental vincaminoreine 2</th>
|
||
<th id="0A5AF26AD13E001CFC30FC83FACEFC88" box="[937,1345,777,792]" colspan="2" colspanRight="1" gridcol="3" gridrow="0" pageId="5" pageNumber="6">published vincaminoreine 2 (Farahanikia et al., 2011)</th>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFCA6FACEFCAD" box="[116,1345,812,829]" gridrow="1" pageId="5" pageNumber="6" rowspan-0="1">
|
||
<td id="0A5AF26AD13E001CFEF8FCA6FDC0FCAD" box="[353,591,812,829]" gridcol="1" gridrow="1" pageId="5" pageNumber="6">500 MHz, CDCl3</td>
|
||
<td id="0A5AF26AD13E001CFD08FCA6FC82FCAD" box="[657,781,812,829]" gridcol="2" gridrow="1" pageId="5" pageNumber="6">125 MHz, CDCl3</td>
|
||
<td id="0A5AF26AD13E001CFC30FCA6FBA9FCAD" box="[937,1062,812,829]" gridcol="3" gridrow="1" pageId="5" pageNumber="6">500 MHz, CDCl3</td>
|
||
<td id="0A5AF26AD13E001CFB5BFCA6FACEFCAD" box="[1218,1345,812,829]" gridcol="4" gridrow="1" pageId="5" pageNumber="6">125 MHz, CDCl3</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFCDAFACEFCCE" box="[116,1345,848,862]" gridrow="2" pageId="5" pageNumber="6" rowspan-1="1" rowspan-3="1">
|
||
<th id="0A5AF26AD13E001CFFEDFCDAFF4AFCCE" box="[116,197,848,862]" gridcol="0" gridrow="2" pageId="5" pageNumber="6">2</th>
|
||
<td id="0A5AF26AD13E001CFD08FCDAFC82FCCE" box="[657,781,848,862]" gridcol="2" gridrow="2" pageId="5" pageNumber="6">139.3</td>
|
||
<td id="0A5AF26AD13E001CFB5BFCDAFACEFCCE" box="[1218,1345,848,862]" gridcol="4" gridrow="2" pageId="5" pageNumber="6">139.3</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFCECFACEFCE5" box="[116,1345,870,885]" gridrow="3" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFCECFF4AFCE5" box="[116,197,870,885]" gridcol="0" gridrow="3" pageId="5" pageNumber="6">3</th>
|
||
<td id="0A5AF26AD13E001CFEF8FCECFDC0FCE5" box="[353,591,870,885]" gridcol="1" gridrow="3" pageId="5" pageNumber="6">3.90, dd (4.8, 2.9)</td>
|
||
<td id="0A5AF26AD13E001CFD08FCECFC82FCE5" box="[657,781,870,885]" gridcol="2" gridrow="3" pageId="5" pageNumber="6">38.1</td>
|
||
<td id="0A5AF26AD13E001CFC30FCECFBA9FCE5" box="[937,1062,870,885]" gridcol="3" gridrow="3" pageId="5" pageNumber="6">1.96–1.93, m</td>
|
||
<td id="0A5AF26AD13E001CFB5BFCECFACEFCE5" box="[1218,1345,870,885]" gridcol="4" gridrow="3" pageId="5" pageNumber="6">33.8</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFCF7FACEFC1C" box="[116,1345,893,908]" gridrow="4" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFCF7FF4AFC1C" box="[116,197,893,908]" gridcol="0" gridrow="4" pageId="5" pageNumber="6">4</th>
|
||
<td id="0A5AF26AD13E001CFEF8FCF7FDC0FC1C" box="[353,591,893,908]" gridcol="1" gridrow="4" pageId="5" pageNumber="6">2.46, dd (13.7, 2.9)</td>
|
||
<td id="0A5AF26AD13E001CFD08FCF7FC82FC1C" box="[657,781,893,908]" gridcol="2" gridrow="4" pageId="5" pageNumber="6">33.9</td>
|
||
<td id="0A5AF26AD13E001CFC30FCF7FBA9FC1C" box="[937,1062,893,908]" gridcol="3" gridrow="4" pageId="5" pageNumber="6">2.95–2.93, m</td>
|
||
<td id="0A5AF26AD13E001CFB5BFCF7FACEFC1C" box="[1218,1345,893,908]" gridcol="4" gridrow="4" pageId="5" pageNumber="6">22.5</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFC1EFACEFC32" box="[116,1345,916,930]" gridrow="5" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFC1EFACEFC32" box="[116,1345,916,930]" colspan="5" colspanRight="4" gridcol="0" gridrow="5" pageId="5" pageNumber="6">1.97, d (13.7)</th>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFC21FACEFC29" box="[116,1345,939,953]" gridrow="6" pageId="5" pageNumber="6" rowspan-1="1" rowspan-3="1">
|
||
<th id="0A5AF26AD13E001CFFEDFC21FF4AFC29" box="[116,197,939,953]" gridcol="0" gridrow="6" pageId="5" pageNumber="6">5</th>
|
||
<td id="0A5AF26AD13E001CFD08FC21FC82FC29" box="[657,781,939,953]" gridcol="2" gridrow="6" pageId="5" pageNumber="6">38.1</td>
|
||
<td id="0A5AF26AD13E001CFB5BFC21FACEFC29" box="[1218,1345,939,953]" gridcol="4" gridrow="6" pageId="5" pageNumber="6">24.8</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFC48FACEFC40" box="[116,1345,962,976]" gridrow="7" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFC48FF4AFC40" box="[116,197,962,976]" gridcol="0" gridrow="7" pageId="5" pageNumber="6">6</th>
|
||
<td id="0A5AF26AD13E001CFEF8FC48FDC0FC40" box="[353,591,962,976]" gridcol="1" gridrow="7" pageId="5" pageNumber="6">1.43–1.36, m</td>
|
||
<td id="0A5AF26AD13E001CFD08FC48FC82FC40" box="[657,781,962,976]" gridcol="2" gridrow="7" pageId="5" pageNumber="6">34.2</td>
|
||
<td id="0A5AF26AD13E001CFC30FC48FBA9FC40" box="[937,1062,962,976]" gridcol="3" gridrow="7" pageId="5" pageNumber="6">1.35–1.30, m</td>
|
||
<td id="0A5AF26AD13E001CFB5BFC48FACEFC40" box="[1218,1345,962,976]" gridcol="4" gridrow="7" pageId="5" pageNumber="6">31.0</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFC53FACEFC77" box="[116,1345,985,999]" gridrow="8" pageId="5" pageNumber="6" rowspan-0="1" rowspan-2="1" rowspan-4="1">
|
||
<td id="0A5AF26AD13E001CFEF8FC53FDC0FC77" box="[353,591,985,999]" gridcol="1" gridrow="8" pageId="5" pageNumber="6">1.24–1.12, m</td>
|
||
<td id="0A5AF26AD13E001CFC30FC53FBA9FC77" box="[937,1062,985,999]" gridcol="3" gridrow="8" pageId="5" pageNumber="6">1.20–1.18, m</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFC7AFACEFC6E" box="[116,1345,1008,1022]" gridrow="9" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFC7AFF4AFC6E" box="[116,197,1008,1022]" gridcol="0" gridrow="9" pageId="5" pageNumber="6">7</th>
|
||
<td id="0A5AF26AD13E001CFEF8FC7AFDC0FC6E" box="[353,591,1008,1022]" gridcol="1" gridrow="9" pageId="5" pageNumber="6">1.54–1.44, m</td>
|
||
<td id="0A5AF26AD13E001CFD08FC7AFC82FC6E" box="[657,781,1008,1022]" gridcol="2" gridrow="9" pageId="5" pageNumber="6">22.5</td>
|
||
<td id="0A5AF26AD13E001CFC30FC7AFBA9FC6E" box="[937,1062,1008,1022]" gridcol="3" gridrow="9" pageId="5" pageNumber="6">1.54–1.47, m</td>
|
||
<td id="0A5AF26AD13E001CFB5BFC7AFACEFC6E" box="[1218,1345,1008,1022]" gridcol="4" gridrow="9" pageId="5" pageNumber="6">22.3</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFB8CFACEFB85" box="[116,1345,1030,1045]" gridrow="10" pageId="5" pageNumber="6" rowspan-0="1" rowspan-2="1" rowspan-4="1">
|
||
<td id="0A5AF26AD13E001CFEF8FB8CFDC0FB85" box="[353,591,1030,1045]" gridcol="1" gridrow="10" pageId="5" pageNumber="6">1.35–1.24, m</td>
|
||
<td id="0A5AF26AD13E001CFC30FB8CFBA9FB85" box="[937,1062,1030,1045]" gridcol="3" gridrow="10" pageId="5" pageNumber="6">1.29–1.25, m</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFB97FACEFBBC" box="[116,1345,1053,1068]" gridrow="11" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFB97FF4AFBBC" box="[116,197,1053,1068]" gridcol="0" gridrow="11" pageId="5" pageNumber="6">8</th>
|
||
<td id="0A5AF26AD13E001CFEF8FB97FDC0FBBC" box="[353,591,1053,1068]" gridcol="1" gridrow="11" pageId="5" pageNumber="6">2.38–2.32, m</td>
|
||
<td id="0A5AF26AD13E001CFD08FB97FC82FBBC" box="[657,781,1053,1068]" gridcol="2" gridrow="11" pageId="5" pageNumber="6">55.3</td>
|
||
<td id="0A5AF26AD13E001CFC30FB97FBA9FBBC" box="[937,1062,1053,1068]" gridcol="3" gridrow="11" pageId="5" pageNumber="6">2.51–2.49, m</td>
|
||
<td id="0A5AF26AD13E001CFB5BFB97FACEFBBC" box="[1218,1345,1053,1068]" gridcol="4" gridrow="11" pageId="5" pageNumber="6">53.3</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFBBEFACEFBD2" box="[116,1345,1076,1090]" gridrow="12" pageId="5" pageNumber="6" rowspan-0="1" rowspan-2="1" rowspan-4="1">
|
||
<td id="0A5AF26AD13E001CFEF8FBBEFDC0FBD2" box="[353,591,1076,1090]" gridcol="1" gridrow="12" pageId="5" pageNumber="6">2.32–2.20, m</td>
|
||
<td id="0A5AF26AD13E001CFC30FBBEFBA9FBD2" box="[937,1062,1076,1090]" gridcol="3" gridrow="12" pageId="5" pageNumber="6">2.27–2.24, m</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFBC1FACEFBC9" box="[116,1345,1099,1113]" gridrow="13" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFBC1FF4AFBC9" box="[116,197,1099,1113]" gridcol="0" gridrow="13" pageId="5" pageNumber="6">10</th>
|
||
<td id="0A5AF26AD13E001CFEF8FBC1FDC0FBC9" box="[353,591,1099,1113]" gridcol="1" gridrow="13" pageId="5" pageNumber="6">2.55–2.50, m</td>
|
||
<td id="0A5AF26AD13E001CFD08FBC1FC82FBC9" box="[657,781,1099,1113]" gridcol="2" gridrow="13" pageId="5" pageNumber="6">53.3</td>
|
||
<td id="0A5AF26AD13E001CFC30FBC1FBA9FBC9" box="[937,1062,1099,1113]" gridcol="3" gridrow="13" pageId="5" pageNumber="6">2.33–2.29, m</td>
|
||
<td id="0A5AF26AD13E001CFB5BFBC1FACEFBC9" box="[1218,1345,1099,1113]" gridcol="4" gridrow="13" pageId="5" pageNumber="6">55.3</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFBE8FACEFBE0" box="[116,1345,1122,1136]" gridrow="14" pageId="5" pageNumber="6" rowspan-0="1" rowspan-2="1" rowspan-4="1">
|
||
<td id="0A5AF26AD13E001CFEF8FBE8FDC0FBE0" box="[353,591,1122,1136]" gridcol="1" gridrow="14" pageId="5" pageNumber="6">2.32–2.20, m</td>
|
||
<td id="0A5AF26AD13E001CFC30FBE8FBA9FBE0" box="[937,1062,1122,1136]" gridcol="3" gridrow="14" pageId="5" pageNumber="6">2.29–2.27, m</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFBF3FACEFB17" box="[116,1345,1145,1159]" gridrow="15" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFBF3FF4AFB17" box="[116,197,1145,1159]" gridcol="0" gridrow="15" pageId="5" pageNumber="6">11</th>
|
||
<td id="0A5AF26AD13E001CFEF8FBF3FDC0FB17" box="[353,591,1145,1159]" gridcol="1" gridrow="15" pageId="5" pageNumber="6">3.00–2.89, m</td>
|
||
<td id="0A5AF26AD13E001CFD08FBF3FC82FB17" box="[657,781,1145,1159]" gridcol="2" gridrow="15" pageId="5" pageNumber="6">22.3</td>
|
||
<td id="0A5AF26AD13E001CFC30FBF3FBA9FB17" box="[937,1062,1145,1159]" gridcol="3" gridrow="15" pageId="5" pageNumber="6">1.41–1.36, m</td>
|
||
<td id="0A5AF26AD13E001CFB5BFBF3FACEFB17" box="[1218,1345,1145,1159]" gridcol="4" gridrow="15" pageId="5" pageNumber="6">34.2</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFB05FACEFB0E" box="[116,1345,1167,1182]" gridrow="16" pageId="5" pageNumber="6" rowspan-0="1" rowspan-1="1" rowspan-2="1" rowspan-4="1">
|
||
<td id="0A5AF26AD13E001CFC30FB05FBA9FB0E" box="[937,1062,1167,1182]" gridcol="3" gridrow="16" pageId="5" pageNumber="6">1.18–1.16, m</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFB2CFACEFB24" box="[116,1345,1190,1204]" gridrow="17" pageId="5" pageNumber="6" rowspan-1="1" rowspan-3="1">
|
||
<th id="0A5AF26AD13E001CFFEDFB2CFF4AFB24" box="[116,197,1190,1204]" gridcol="0" gridrow="17" pageId="5" pageNumber="6">12</th>
|
||
<td id="0A5AF26AD13E001CFD08FB2CFC82FB24" box="[657,781,1190,1204]" gridcol="2" gridrow="17" pageId="5" pageNumber="6">110.0</td>
|
||
<td id="0A5AF26AD13E001CFB5BFB2CFACEFB24" box="[1218,1345,1190,1204]" gridcol="4" gridrow="17" pageId="5" pageNumber="6">110.0</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFB37FACEFB5B" box="[116,1345,1213,1227]" gridrow="18" pageId="5" pageNumber="6" rowspan-1="1" rowspan-3="1">
|
||
<th id="0A5AF26AD13E001CFFEDFB37FF4AFB5B" box="[116,197,1213,1227]" gridcol="0" gridrow="18" pageId="5" pageNumber="6">13</th>
|
||
<td id="0A5AF26AD13E001CFD08FB37FC82FB5B" box="[657,781,1213,1227]" gridcol="2" gridrow="18" pageId="5" pageNumber="6">127.1</td>
|
||
<td id="0A5AF26AD13E001CFB5BFB37FACEFB5B" box="[1218,1345,1213,1227]" gridcol="4" gridrow="18" pageId="5" pageNumber="6">127.1</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFB5EFACEFB72" box="[116,1345,1236,1250]" gridrow="19" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFB5EFF4AFB72" box="[116,197,1236,1250]" gridcol="0" gridrow="19" pageId="5" pageNumber="6">14</th>
|
||
<td id="0A5AF26AD13E001CFEF8FB5EFDC0FB72" box="[353,591,1236,1250]" gridcol="1" gridrow="19" pageId="5" pageNumber="6">7.50, dd (7.8, 1.0)</td>
|
||
<td id="0A5AF26AD13E001CFD08FB5EFC82FB72" box="[657,781,1236,1250]" gridcol="2" gridrow="19" pageId="5" pageNumber="6">118.0</td>
|
||
<td id="0A5AF26AD13E001CFC30FB5EFBA9FB72" box="[937,1062,1236,1250]" gridcol="3" gridrow="19" pageId="5" pageNumber="6">7.50, d (7.1)</td>
|
||
<td id="0A5AF26AD13E001CFB5BFB5EFACEFB72" box="[1218,1345,1236,1250]" gridcol="4" gridrow="19" pageId="5" pageNumber="6">118.0</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFB61FACEFB69" box="[116,1345,1259,1273]" gridrow="20" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFB61FF4AFB69" box="[116,197,1259,1273]" gridcol="0" gridrow="20" pageId="5" pageNumber="6">15</th>
|
||
<td id="0A5AF26AD13E001CFEF8FB61FDC0FB69" box="[353,591,1259,1273]" gridcol="1" gridrow="20" pageId="5" pageNumber="6">7.18, td (7.8, 1.0)</td>
|
||
<td id="0A5AF26AD13E001CFD08FB61FC82FB69" box="[657,781,1259,1273]" gridcol="2" gridrow="20" pageId="5" pageNumber="6">118.5</td>
|
||
<td id="0A5AF26AD13E001CFC30FB61FBA9FB69" box="[937,1062,1259,1273]" gridcol="3" gridrow="20" pageId="5" pageNumber="6">7.17, t (7.0)</td>
|
||
<td id="0A5AF26AD13E001CFB5BFB61FACEFB69" box="[1218,1345,1259,1273]" gridcol="4" gridrow="20" pageId="5" pageNumber="6">120.6</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFA88FACEFA80" box="[116,1345,1282,1296]" gridrow="21" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFA88FF4AFA80" box="[116,197,1282,1296]" gridcol="0" gridrow="21" pageId="5" pageNumber="6">16</th>
|
||
<td id="0A5AF26AD13E001CFEF8FA88FDC0FA80" box="[353,591,1282,1296]" gridcol="1" gridrow="21" pageId="5" pageNumber="6">7.09, td (7.8, 1.0)</td>
|
||
<td id="0A5AF26AD13E001CFD08FA88FC82FA80" box="[657,781,1282,1296]" gridcol="2" gridrow="21" pageId="5" pageNumber="6">120.6</td>
|
||
<td id="0A5AF26AD13E001CFC30FA88FBA9FA80" box="[937,1062,1282,1296]" gridcol="3" gridrow="21" pageId="5" pageNumber="6">7.07, t (7.0)</td>
|
||
<td id="0A5AF26AD13E001CFB5BFA88FACEFA80" box="[1218,1345,1282,1296]" gridcol="4" gridrow="21" pageId="5" pageNumber="6">118.5</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFA93FACEFAB7" box="[116,1345,1305,1319]" gridrow="22" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFA93FF4AFAB7" box="[116,197,1305,1319]" gridcol="0" gridrow="22" pageId="5" pageNumber="6">17</th>
|
||
<td id="0A5AF26AD13E001CFEF8FA93FDC0FAB7" box="[353,591,1305,1319]" gridcol="1" gridrow="22" pageId="5" pageNumber="6">7.26, dd (7.8, 1.0)</td>
|
||
<td id="0A5AF26AD13E001CFD08FA93FC82FAB7" box="[657,781,1305,1319]" gridcol="2" gridrow="22" pageId="5" pageNumber="6">108.6</td>
|
||
<td id="0A5AF26AD13E001CFC30FA93FBA9FAB7" box="[937,1062,1305,1319]" gridcol="3" gridrow="22" pageId="5" pageNumber="6">7.24, overlap</td>
|
||
<td id="0A5AF26AD13E001CFB5BFA93FACEFAB7" box="[1218,1345,1305,1319]" gridcol="4" gridrow="22" pageId="5" pageNumber="6">108.6</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFAA5FACEFAAE" box="[116,1345,1327,1342]" gridrow="23" pageId="5" pageNumber="6" rowspan-1="1" rowspan-3="1">
|
||
<th id="0A5AF26AD13E001CFFEDFAA5FF4AFAAE" box="[116,197,1327,1342]" gridcol="0" gridrow="23" pageId="5" pageNumber="6">18</th>
|
||
<td id="0A5AF26AD13E001CFD08FAA5FC82FAAE" box="[657,781,1327,1342]" gridcol="2" gridrow="23" pageId="5" pageNumber="6">136.8</td>
|
||
<td id="0A5AF26AD13E001CFB5BFAA5FACEFAAE" box="[1218,1345,1327,1342]" gridcol="4" gridrow="23" pageId="5" pageNumber="6">136.7</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFACCFACEFAC4" box="[116,1345,1350,1364]" gridrow="24" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFACCFF4AFAC4" box="[116,197,1350,1364]" gridcol="0" gridrow="24" pageId="5" pageNumber="6">19</th>
|
||
<td id="0A5AF26AD13E001CFEF8FACCFDC0FAC4" box="[353,591,1350,1364]" gridcol="1" gridrow="24" pageId="5" pageNumber="6">3.16, d (12.5)</td>
|
||
<td id="0A5AF26AD13E001CFD08FACCFC82FAC4" box="[657,781,1350,1364]" gridcol="2" gridrow="24" pageId="5" pageNumber="6">57.9</td>
|
||
<td id="0A5AF26AD13E001CFC30FACCFBA9FAC4" box="[937,1062,1350,1364]" gridcol="3" gridrow="24" pageId="5" pageNumber="6">3.16, d (15.0)</td>
|
||
<td id="0A5AF26AD13E001CFB5BFACCFACEFAC4" box="[1218,1345,1350,1364]" gridcol="4" gridrow="24" pageId="5" pageNumber="6">57.9</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFAD7FACEFAFB" box="[116,1345,1373,1387]" gridrow="25" pageId="5" pageNumber="6" rowspan-0="1" rowspan-2="1" rowspan-4="1">
|
||
<td id="0A5AF26AD13E001CFEF8FAD7FDC0FAFB" box="[353,591,1373,1387]" gridcol="1" gridrow="25" pageId="5" pageNumber="6">1.61, d (12.5)</td>
|
||
<td id="0A5AF26AD13E001CFC30FAD7FBA9FAFB" box="[937,1062,1373,1387]" gridcol="3" gridrow="25" pageId="5" pageNumber="6">1.61, d (15.0)</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFAFEFACEFA12" box="[116,1345,1396,1410]" gridrow="26" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFAFEFF4AFA12" box="[116,197,1396,1410]" gridcol="0" gridrow="26" pageId="5" pageNumber="6">20</th>
|
||
<td id="0A5AF26AD13E001CFEF8FAFEFDC0FA12" box="[353,591,1396,1410]" gridcol="1" gridrow="26" pageId="5" pageNumber="6">1.35–1.24, m</td>
|
||
<td id="0A5AF26AD13E001CFD08FAFEFC82FA12" box="[657,781,1396,1410]" gridcol="2" gridrow="26" pageId="5" pageNumber="6">31.0</td>
|
||
<td id="0A5AF26AD13E001CFC30FAFEFBA9FA12" box="[937,1062,1396,1410]" gridcol="3" gridrow="26" pageId="5" pageNumber="6">1.25–1.20, m</td>
|
||
<td id="0A5AF26AD13E001CFB5BFAFEFACEFA12" box="[1218,1345,1396,1410]" gridcol="4" gridrow="26" pageId="5" pageNumber="6">14.2</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFA01FACEFA09" box="[116,1345,1419,1433]" gridrow="27" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFA01FACEFA09" box="[116,1345,1419,1433]" colspan="5" colspanRight="4" gridcol="0" gridrow="27" pageId="5" pageNumber="6">1.24–1.12, m</th>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFA28FACEFA20" box="[116,1345,1442,1456]" gridrow="28" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFA28FF4AFA20" box="[116,197,1442,1456]" gridcol="0" gridrow="28" pageId="5" pageNumber="6">21</th>
|
||
<td id="0A5AF26AD13E001CFEF8FA28FDC0FA20" box="[353,591,1442,1456]" gridcol="1" gridrow="28" pageId="5" pageNumber="6">0.95, t (7.5)</td>
|
||
<td id="0A5AF26AD13E001CFD08FA28FC82FA20" box="[657,781,1442,1456]" gridcol="2" gridrow="28" pageId="5" pageNumber="6">7.4</td>
|
||
<td id="0A5AF26AD13E001CFC30FA28FBA9FA20" box="[937,1062,1442,1456]" gridcol="3" gridrow="28" pageId="5" pageNumber="6">0.93, t (7.2)</td>
|
||
<td id="0A5AF26AD13E001CFB5BFA28FACEFA20" box="[1218,1345,1442,1456]" gridcol="4" gridrow="28" pageId="5" pageNumber="6">7.4</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFA33FACEFA57" box="[116,1345,1465,1479]" gridrow="29" pageId="5" pageNumber="6" rowspan-1="1" rowspan-3="1">
|
||
<th id="0A5AF26AD13E001CFFEDFA33FF4AFA57" box="[116,197,1465,1479]" gridcol="0" gridrow="29" pageId="5" pageNumber="6">C= O</th>
|
||
<td id="0A5AF26AD13E001CFD08FA33FC82FA57" box="[657,781,1465,1479]" gridcol="2" gridrow="29" pageId="5" pageNumber="6">175.2</td>
|
||
<td id="0A5AF26AD13E001CFB5BFA33FACEFA57" box="[1218,1345,1465,1479]" gridcol="4" gridrow="29" pageId="5" pageNumber="6">175.2</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFA45FACEFA70" box="[116,1345,1487,1504]" gridrow="30" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFA45FF4AFA70" box="[116,197,1487,1504]" gridcol="0" gridrow="30" pageId="5" pageNumber="6">3-COOCH3</th>
|
||
<td id="0A5AF26AD13E001CFEF8FA45FDC0FA70" box="[353,591,1487,1504]" gridcol="1" gridrow="30" pageId="5" pageNumber="6">3.71, s</td>
|
||
<td id="0A5AF26AD13E001CFD08FA45FC82FA70" box="[657,781,1487,1504]" gridcol="2" gridrow="30" pageId="5" pageNumber="6">52.5</td>
|
||
<td id="0A5AF26AD13E001CFC30FA45FBA9FA70" box="[937,1062,1487,1504]" gridcol="3" gridrow="30" pageId="5" pageNumber="6">3.70, s</td>
|
||
<td id="0A5AF26AD13E001CFB5BFA45FACEFA70" box="[1218,1345,1487,1504]" gridcol="4" gridrow="30" pageId="5" pageNumber="6">52.5</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFA6CFACEFA67" box="[116,1345,1510,1527]" gridrow="31" pageId="5" pageNumber="6">
|
||
<th id="0A5AF26AD13E001CFFEDFA6CFF4AFA67" box="[116,197,1510,1527]" gridcol="0" gridrow="31" pageId="5" pageNumber="6">NCH3</th>
|
||
<td id="0A5AF26AD13E001CFEF8FA6CFDC0FA67" box="[353,591,1510,1527]" gridcol="1" gridrow="31" pageId="5" pageNumber="6">3.54, s</td>
|
||
<td id="0A5AF26AD13E001CFD08FA6CFC82FA67" box="[657,781,1510,1527]" gridcol="2" gridrow="31" pageId="5" pageNumber="6">30.2</td>
|
||
<td id="0A5AF26AD13E001CFC30FA6CFBA9FA67" box="[937,1062,1510,1527]" gridcol="3" gridrow="31" pageId="5" pageNumber="6">3.52, s</td>
|
||
<td id="0A5AF26AD13E001CFB5BFA6CFACEFA67" box="[1218,1345,1510,1527]" gridcol="4" gridrow="31" pageId="5" pageNumber="6">30.2</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDFA77FACEF99E" box="[116,1345,1533,1550]" gridrow="32" pageId="5" pageNumber="6" rowspan-2="1" rowspan-4="1">
|
||
<th id="0A5AF26AD13E001CFFEDFA77FF4AF99E" box="[116,197,1533,1550]" gridcol="0" gridrow="32" pageId="5" pageNumber="6">[a]D</th>
|
||
<td id="0A5AF26AD13E001CFEF8FA77FDC0F99E" box="[353,591,1533,1550]" gridcol="1" gridrow="32" pageId="5" pageNumber="6">+ 27.6 (c 0.18, CHCl3)</td>
|
||
<td id="0A5AF26AD13E001CFC30FA77FBA9F99E" box="[937,1062,1533,1550]" gridcol="3" gridrow="32" pageId="5" pageNumber="6">+ 26.5 (CHCl3)</td>
|
||
</tr>
|
||
<tr id="498B9B16D13E001CFFEDF99EFACEF9B2" box="[116,1345,1556,1570]" gridrow="33" pageId="5" pageNumber="6" rowspan-0="1" rowspan-1="1" rowspan-2="1">
|
||
<td id="0A5AF26AD13E001CFC30F99EFACEF9B2" box="[937,1345,1556,1570]" colspan="2" colspanRight="1" gridcol="3" gridrow="33" pageId="5" pageNumber="6">(Farahanikia et al., 2011; Mokrý et al., 1964)</td>
|
||
</tr>
|
||
</table>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13EFFE6FF1DF942FD4CF8F6" blockId="5.[100,771,1624,1979]" pageId="5" pageNumber="6">
|
||
Since GSK-3β is involved in the formation of Aβ and NFTs in AD, it can be considered a promising target for developing antidementia drugs. Thus, alkaloid
|
||
<emphasis id="C5CF4546D13EFFE6FF77F88AFE88F883" bold="true" box="[238,263,1792,1811]" pageId="5" pageNumber="6">19</emphasis>
|
||
, as the most active compound from the cholinesterase and POP inhibition assays, was also screened for its GSK-3β inhibition potency at a concentration of 100 μM. However, it showed only marginal inhibition potential (31.43 ± 3.05% inhibition of GSK-3β).
|
||
</paragraph>
|
||
<paragraph id="F7049954D13EFFE6FF1DF8FAFBA6F8BF" blockId="5.[100,771,1624,1979]" lastBlockId="5.[818,1488,1624,1979]" pageId="5" pageNumber="6">
|
||
An enzyme kinetic study was carried out to explore the inhibition mechanism of active compound
|
||
<emphasis id="C5CF4546D13EFFE6FE2BF801FE44F80E" bold="true" box="[434,459,1931,1950]" pageId="5" pageNumber="6">19</emphasis>
|
||
with
|
||
<emphasis id="C5CF4546D13EFFE6FD88F801FD93F80E" bold="true" box="[529,540,1931,1950]" italics="true" pageId="5" pageNumber="6">h</emphasis>
|
||
BuChE to describe the involved interaction. Inhibition kinetics was determined from velocity curves measured at different concentrations of
|
||
<emphasis id="C5CF4546D13EFFE6FB76F9D2FA87F9FB" bold="true" box="[1263,1288,1624,1643]" pageId="5" pageNumber="6">19</emphasis>
|
||
. The
|
||
<typeStatus id="280027F6D13EFFE6FAA6F9D3FAE7F9FC" box="[1343,1384,1625,1644]" pageId="5" pageNumber="6">type</typeStatus>
|
||
of enzyme inhibition and appropriate affinity parameter (
|
||
<emphasis id="C5CF4546D13EFFE6FB65F9FEFA85F917" bold="true" box="[1276,1290,1652,1671]" italics="true" pageId="5" pageNumber="6">K</emphasis>
|
||
<subScript id="6B3F9B11D13EFFE6FA93F9F1FA80F919" attach="left" box="[1290,1295,1659,1673]" fontSize="6" pageId="5" pageNumber="6">i</subScript>
|
||
) was calculated by nonlinear regression analysis. Results for each
|
||
<typeStatus id="280027F6D13EFFE6FB77F91BFA98F934" box="[1262,1303,1681,1700]" pageId="5" pageNumber="6">type</typeStatus>
|
||
of model of inhibition (competitive, non-competitive, uncompetitive, and mixed) were compared by the sum-of-squares F-test. Statistical analysis showed a competitive
|
||
<typeStatus id="280027F6D13EFFE6FC31F96EFC5EF967" box="[936,977,1764,1783]" pageId="5" pageNumber="6">type</typeStatus>
|
||
of inhibition (p ˂ 0.05), which is in accordance with the Lineweaver–Burk (double reciprocal) plot, used for visualization of the obtained data (
|
||
<figureCitation id="6F8085D1D13EFFE6FC7FF896FB94F8BF" box="[998,1051,1820,1839]" captionStart="Fig" captionStartId="7.[100,130,658,675]" captionTargetBox="[107,766,149,630]" captionTargetId="figure-1023@7.[106,767,148,631]" captionTargetPageId="7" captionText="Fig. 4. Steady state competitive type inhibition of hBuChE substrate hydrolysis by active compound 19 at different concentrations. Lineweaver Burk plots of initial velocity at increasing substrate concentrations (2.5–10.0 mM) are presented. Lines were derived from a linear regression of the data points. All measurements were made in triplicate and averaged." figureDoi="http://doi.org/10.5281/zenodo.8240074" httpUri="https://zenodo.org/record/8240074/files/figure.png" pageId="5" pageNumber="6">Fig. 4</figureCitation>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D13EFFE6FCC8F8B2FBACF82A" blockId="5.[818,1488,1624,1979]" pageId="5" pageNumber="6">
|
||
The intersection of lines is located on the y-axis, which means reversible competitive binding mode to the active site of the enzyme. With increasing concentration of inhibitor, the apparent
|
||
<emphasis id="C5CF4546D13EFFE6FADCF8FAFADCF813" bold="true" box="[1349,1363,1904,1923]" italics="true" pageId="5" pageNumber="6">V</emphasis>
|
||
<subScript id="6B3F9B11D13EFFE6FACAF8FDFAFEF815" attach="left" box="[1363,1393,1911,1925]" fontSize="6" pageId="5" pageNumber="6">max</subScript>
|
||
remained unchanged and
|
||
<emphasis id="C5CF4546D13EFFE6FC53F801FC57F80E" bold="true" box="[970,984,1931,1950]" italics="true" pageId="5" pageNumber="6">K</emphasis>
|
||
<subScript id="6B3F9B11D13EFFE6FC41F819FC69F831" attach="left" box="[984,998,1939,1953]" fontSize="6" pageId="5" pageNumber="6">m</subScript>
|
||
increased. A
|
||
<emphasis id="C5CF4546D13EFFE6FBF0F801FBF8F80E" bold="true" box="[1129,1143,1931,1950]" italics="true" pageId="5" pageNumber="6">K</emphasis>
|
||
<subScript id="6B3F9B11D13EFFE6FBEEF818FBF3F830" attach="left" box="[1143,1148,1938,1952]" fontSize="6" pageId="5" pageNumber="6">i</subScript>
|
||
value of 54.9 ± 8.8 nM was determined for
|
||
<emphasis id="C5CF4546D13EFFE6FC0DF82DFC22F82A" bold="true" box="[916,941,1959,1978]" pageId="5" pageNumber="6">16</emphasis>
|
||
on
|
||
<emphasis id="C5CF4546D13EFFE6FC48F82DFC53F82A" bold="true" box="[977,988,1959,1978]" italics="true" pageId="5" pageNumber="6">h</emphasis>
|
||
BuChE.
|
||
</paragraph>
|
||
<caption id="A3C4C9DCD13DFFE5FFFDFDDEFDC8FD22" ID-DOI="http://doi.org/10.5281/zenodo.8240072" ID-Zenodo-Dep="8240072" httpUri="https://zenodo.org/record/8240072/files/figure.png" pageId="6" pageNumber="7" startId="6.[100,130,596,613]" targetBox="[106,764,148,568]" targetPageId="6" targetType="figure">
|
||
<paragraph id="F7049954D13DFFE5FFFDFDDEFDC8FD22" blockId="6.[100,771,596,690]" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FFFDFDDEFF11FDF5" bold="true" box="[100,158,596,613]" pageId="6" pageNumber="7">Fig. 3.</emphasis>
|
||
Described key 2D NMR correlations of revision of previously assigned positions in molecule
|
||
<emphasis id="C5CF4546D13DFFE5FEBFFDE4FEB3FDEF" bold="true" box="[294,316,622,639]" pageId="6" pageNumber="7">17</emphasis>
|
||
(COSY interaction – red bond, HMBC interaction – blue arrow). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
|
||
</paragraph>
|
||
</caption>
|
||
<paragraph id="F7049954D13DFFE5FF1DFD51FC68FEFA" blockId="6.[100,770,731,946]" lastBlockId="6.[818,1487,148,362]" pageId="6" pageNumber="7">
|
||
The crucial requirement for a compound to be of clinical relevance for AD is its CNS availability; thus, the compound must penetrate through the blood-brain barrier. One of the fastest methods to predict that is the calculation of logBB, the logarithmic ratio between the concentration of a compound in the brain and blood. Compounds with logBB
|
||
<emphasis id="C5CF4546D13DFFE5FF38FCEDFF3EFCEA" box="[161,177,871,890]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
0.3 have a very high probability of easy penetration by passive diffusion, whereas compounds with logBB
|
||
<emphasis id="C5CF4546D13DFFE5FD98FC08FD9EFC05" box="[513,529,898,917]" italics="true" pageId="6" pageNumber="7"><</emphasis>
|
||
1 are unlikely to pass; values between 0.3 and 1 still mean the theoretical ability for penetration (Kunwittaya et al., 2013). According to this method, all
|
||
<emphasis id="C5CF4546D13DFFE5FCABFF25FCB2FF52" bold="true" box="[818,829,175,194]" italics="true" pageId="6" pageNumber="7">h</emphasis>
|
||
BuChE active alkaloids (IC
|
||
<subScript id="6B3F9B11D13DFFE5FBD7FF3DFB13FF55" attach="left" box="[1102,1180,182,197]" fontSize="6" pageId="6" pageNumber="7">
|
||
50,
|
||
<emphasis id="C5CF4546D13DFFE5FBFDFF3CFBE3FF54" bold="true" box="[1124,1132,182,196]" italics="true" pageId="6" pageNumber="7">h</emphasis>
|
||
BuChE
|
||
</subScript>
|
||
<emphasis id="C5CF4546D13DFFE5FB33FF3AFB35FF53" box="[1194,1210,176,195]" italics="true" pageId="6" pageNumber="7"><</emphasis>
|
||
10 μM) comply with this requirement (
|
||
<tableCitation id="BA39ACEFD13DFFE5FC2AFF41FC77FF4F" box="[947,1016,203,223]" captionStart="Table 3" captionStartId="6.[100,150,1013,1029]" captionTargetPageId="6" captionText="Table 3 Biological activities of isolated Vinca minor alkaloids." httpUri="http://table.plazi.org/id/A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" pageId="6" pageNumber="7" tableUuid="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F">Table 3</tableCitation>
|
||
). Another commonly employed method to predict the availability of the compound to the CNS is
|
||
<emphasis id="C5CF4546D13DFFE5FB75FF6DFAA3FF6A" bold="true" box="[1260,1324,231,250]" italics="true" pageId="6" pageNumber="7">in vitro</emphasis>
|
||
parallel artificial membrane permeability assessment (PAMPA). Based on the obtained results for
|
||
<emphasis id="C5CF4546D13DFFE5FC0DFE95FC5CFEA2" bold="true" box="[916,979,287,306]" italics="true" pageId="6" pageNumber="7">in vitro</emphasis>
|
||
permeability of
|
||
<emphasis id="C5CF4546D13DFFE5FBF2FE95FB0BFEA2" bold="true" box="[1131,1156,287,306]" pageId="6" pageNumber="7">19</emphasis>
|
||
(
|
||
<emphasis id="C5CF4546D13DFFE5FB08FE95FB29FEA2" bold="true" box="[1169,1190,287,306]" italics="true" pageId="6" pageNumber="7">Pe</emphasis>
|
||
= 15.7 ± 1.3 × 10
|
||
<quantity id="304334B1D13DFFE5FAFBFE93FA03FEA3" box="[1378,1420,281,307]" metricMagnitude="-2" metricUnit="m" metricValue="6.0" pageId="6" pageNumber="7" unit="cm" value="6.0">
|
||
<superScript id="00CE341CD13DFFE5FAFBFE93FAE4FEB7" attach="right" box="[1378,1387,281,295]" fontSize="6" pageId="6" pageNumber="7">6</superScript>
|
||
cm
|
||
</quantity>
|
||
s
|
||
<superScript id="00CE341CD13DFFE5FA3CFE93FA21FEB7" attach="right" box="[1445,1454,281,295]" fontSize="6" pageId="6" pageNumber="7">1</superScript>
|
||
), it can be concluded that this indole alkaloid can cross the BBB by passive diffusion (
|
||
<tableCitation id="BA39ACEFD13DFFE5FC0AFEDDFC56FEFA" box="[915,985,343,362]" captionStart="Table 3" captionStartId="6.[100,150,1013,1029]" captionTargetPageId="6" captionText="Table 3 Biological activities of isolated Vinca minor alkaloids." httpUri="http://table.plazi.org/id/A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" pageId="6" pageNumber="7" tableUuid="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F">Table 3</tableCitation>
|
||
).
|
||
</paragraph>
|
||
</subSubSection>
|
||
<subSubSection id="BFA1CADFD13DFFE4FCABFE2EFB01FC24" lastPageId="7" lastPageNumber="8" pageId="6" pageNumber="7" type="discussion">
|
||
<paragraph id="F7049954D13DFFE5FCABFE2EFA2BFE27" blockId="6.[818,1444,420,439]" box="[818,1444,420,439]" pageId="6" pageNumber="7">
|
||
<heading id="AC4C2E38D13DFFE5FCABFE2EFA2BFE27" bold="true" box="[818,1444,420,439]" fontSize="36" level="1" pageId="6" pageNumber="7" reason="1">
|
||
<emphasis id="C5CF4546D13DFFE5FCABFE2EFA2BFE27" bold="true" box="[818,1444,420,439]" italics="true" pageId="6" pageNumber="7">2.3. Docking study of ()-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13DFFE5FCABFE4AFC15FE43" blockId="6.[818,922,448,467]" box="[818,922,448,467]" pageId="6" pageNumber="7">
|
||
<heading id="AC4C2E38D13DFFE5FCABFE4AFC15FE43" box="[818,922,448,467]" fontSize="8" level="3" pageId="6" pageNumber="7" reason="8">
|
||
<emphasis id="C5CF4546D13DFFE5FCABFE4AFC15FE43" bold="true" box="[818,922,448,467]" italics="true" pageId="6" pageNumber="7">indole (19)</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13DFFE5FCC8FE72FAB9FD07" blockId="6.[818,1488,504,969]" pageId="6" pageNumber="7">
|
||
A molecular dynamic simulation was performed to determine the structural aspects crucial for the high BuChE inhibition ability of 19. The template structure of
|
||
<emphasis id="C5CF4546D13DFFE5FB99FDA5FB84FDD2" bold="true" box="[1024,1035,559,578]" italics="true" pageId="6" pageNumber="7">h</emphasis>
|
||
BuChE was taken from Protein Data Bank (PDB ID: 4BDS) (Nachon et al., 2013). The result was compared with a crystal structure of tacrine, the first FDA-approved drug for AD therapy acting as a dual AChE/BuChE inhibitor (Soukup et al., 2013).
|
||
</paragraph>
|
||
<paragraph id="F7049954D13DFFE4FCC8FD15FE4DFCD5" blockId="6.[818,1488,504,969]" lastBlockId="7.[100,770,818,1340]" lastPageId="7" lastPageNumber="8" pageId="6" pageNumber="7">
|
||
Molecular dynamic simulation of
|
||
<emphasis id="C5CF4546D13DFFE5FB0DFD15FB22FD22" bold="true" box="[1172,1197,671,690]" pageId="6" pageNumber="7">19</emphasis>
|
||
within the
|
||
<emphasis id="C5CF4546D13DFFE5FA87FD15FAA6FD22" bold="true" box="[1310,1321,671,690]" italics="true" pageId="6" pageNumber="7">h</emphasis>
|
||
BuChE active site revealed several crucial interactions responsible for high ligand affinity (
|
||
<figureCitation id="6F8085D1D13DFFE5FCA3FD5DFC31FD7A" box="[826,958,727,746]" captionStart="Fig" captionStartId="8.[100,130,1178,1195]" captionTargetBox="[208,1380,149,1150]" captionTargetId="figure-560@8.[206,1381,148,1151]" captionTargetPageId="8" captionText="Fig. 5. The top-scored docking poses of 19 in hBuChE (A, B; PDB ID: 4BDS) and the crystal structure of tacrine bound to hBuChE (C, D). The ligands are displayed in blue (A) and green (C) for 19 and tacrine, respectively; important amino acid residues responsible for ligand anchoring are shown in grey for hBuChE (A, C). Catalytic triad residues are displayed in yellow (A, C). Important interactions are rendered by black dashed lines; distances are measured in angstroms (Å). The rest of the receptor is displayed in light-grey cartoon conformation (A, C). Figures A and C were created with The PyMOL Molecular Graphics System, Version 2.4.1, Schr¨odinger, LLC. 2D figures (B, D) were generated with Maestro 12.3 (Schr¨odinger Release, Schr¨odinger, LLC, New York, NY, 2020). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)" figureDoi="http://doi.org/10.5281/zenodo.8240076" httpUri="https://zenodo.org/record/8240076/files/figure.png" pageId="6" pageNumber="7">Fig. 5A and B</figureCitation>
|
||
). The 2-ethyl-1
|
||
<emphasis id="C5CF4546D13DFFE5FBD7FD5DFBD2FD7A" bold="true" box="[1102,1117,727,746]" italics="true" pageId="6" pageNumber="7">H</emphasis>
|
||
-indole moiety of
|
||
<emphasis id="C5CF4546D13DFFE5FA9FFD5DFA90FD7A" bold="true" box="[1286,1311,727,746]" pageId="6" pageNumber="7">19</emphasis>
|
||
is engaged in parallel π- π and displaced π- π stackings with Y440 (4.2 Å) and W430 (4.7 Å), respectively. Moreover, the 2-ethyl-1
|
||
<emphasis id="C5CF4546D13DFFE5FB12FC85FB15FCB2" bold="true" box="[1163,1178,783,802]" italics="true" pageId="6" pageNumber="7">H</emphasis>
|
||
-indole moiety lies in the vicinity of W82 (4.3 Å). The hydrogen atom of the indole moiety contacts the amide backbone of H438 from the catalytic triad via hydrogen bond interaction (1.9 Å). Other catalytic triad residues (S198, E325) stand aside from
|
||
<emphasis id="C5CF4546D13DFFE5FC07FCF5FC38FC02" bold="true" box="[926,951,895,914]" pageId="6" pageNumber="7">19</emphasis>
|
||
. The protonated nitrogen atom of the 3-ethylpiperidine moiety faces towards Y332 (4.5 Å) by providing cation-π interaction. Besides, the ethyl appendage of 3-ethylpiperidine occupies the hydrophobic region formed by F329.
|
||
</paragraph>
|
||
<caption id="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" ID-Table-UUID="A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" httpUri="http://table.plazi.org/id/A3C4C9DCD13DFFE5FFFDFC7FFDA6FB8F" pageId="6" pageNumber="7" startId="6.[100,150,1013,1029]" targetBox="[116,1464,1071,1764]" targetIsTable="true" targetPageId="6" targetType="table">
|
||
<paragraph id="F7049954D13DFFE5FFFDFC7FFF28FB96" blockId="6.[100,553,1013,1055]" box="[100,167,1013,1030]" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FFFDFC7FFF28FB96" bold="true" box="[100,167,1013,1030]" pageId="6" pageNumber="7">Table 3</emphasis>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13DFFE5FFFDFB84FDA6FB8F" blockId="6.[100,553,1013,1055]" box="[100,553,1038,1055]" pageId="6" pageNumber="7">
|
||
Biological activities of isolated
|
||
<taxonomicName id="30BBE2D7D13DFFE5FEF7FB84FE5EFB8F" box="[366,465,1038,1055]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="6" pageNumber="7" phylum="Tracheophyta" rank="species" species="minor">
|
||
<emphasis id="C5CF4546D13DFFE5FEF7FB84FE5EFB8F" bold="true" box="[366,465,1038,1055]" italics="true" pageId="6" pageNumber="7">Vinca minor</emphasis>
|
||
</taxonomicName>
|
||
alkaloids.
|
||
</paragraph>
|
||
</caption>
|
||
<paragraph id="F7049954D13DFFE5FFEDFBB9FA28F974" pageId="6" pageNumber="7">
|
||
<table id="85BB6BF4D13D001CFFEDFBA5FA37F974" box="[116,1464,1071,1764]" gridcols="8" gridrows="29" pageId="6" pageNumber="7">
|
||
<tr id="498B9B16D13D001CFFEDFBA5FA37FBCA" box="[116,1464,1071,1114]" gridrow="0" pageId="6" pageNumber="7">
|
||
<th id="0A5AF26AD13D001CFFEDFBA5FE39FBCA" box="[116,438,1071,1114]" gridcol="0" gridrow="0" pageId="6" pageNumber="7">Compound</th>
|
||
<th id="0A5AF26AD13D001CFE79FBA5FDFFFBCA" box="[480,624,1071,1114]" gridcol="1" gridrow="0" pageId="6" pageNumber="7">
|
||
IC50
|
||
<emphasis id="C5CF4546D13DFFE5FD9DFBB9FD82FBD1" bold="true" box="[516,525,1075,1089]" italics="true" pageId="6" pageNumber="7">h</emphasis>
|
||
AChE ± SEM (μM) a
|
||
</th>
|
||
<th id="0A5AF26AD13D001CFD0BFBA5FCA5FBCA" box="[658,810,1071,1114]" gridcol="2" gridrow="0" pageId="6" pageNumber="7">
|
||
IC50
|
||
<emphasis id="C5CF4546D13DFFE5FD2FFBB9FD30FBD1" bold="true" box="[694,703,1075,1089]" italics="true" pageId="6" pageNumber="7">h</emphasis>
|
||
BuChE ± SEM (μM) a
|
||
</th>
|
||
<th id="0A5AF26AD13D001CFCD4FBA5FC45FBCA" box="[845,970,1071,1114]" gridcol="3" gridrow="0" pageId="6" pageNumber="7">IC50 POP ± SEM (μM) a</th>
|
||
<th id="0A5AF26AD13D001CFC77FBA5FB14FBCA" box="[1006,1179,1071,1114]" gridcol="4" gridrow="0" pageId="6" pageNumber="7">% inhibition of GSK-3β SEM b ±</th>
|
||
<th id="0A5AF26AD13D001CFB5EFBA5FA8CFBCA" box="[1223,1283,1071,1114]" gridcol="5" gridrow="0" pageId="6" pageNumber="7">logBB c</th>
|
||
<th id="0A5AF26AD13D001CFAB8FBA5FA37FBCA" box="[1313,1464,1071,1114]" colspan="2" colspanRight="1" gridcol="6" gridrow="0" pageId="6" pageNumber="7">
|
||
PAMPA (
|
||
<emphasis id="C5CF4546D13DFFE5FAFFFBB9FAFFFBD1" bold="true" box="[1382,1392,1075,1089]" italics="true" pageId="6" pageNumber="7">P</emphasis>
|
||
e; 10 6 cm s 1)d
|
||
</th>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFBE7FA37FBEB" box="[116,1464,1133,1147]" gridrow="1" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFBE7FE39FBEB" box="[116,438,1133,1147]" gridcol="0" gridrow="1" pageId="6" pageNumber="7">
|
||
vincaminorine (
|
||
<emphasis id="C5CF4546D13DFFE5FF75FBE7FF79FBEB" bold="true" box="[236,246,1133,1147]" pageId="6" pageNumber="7">1</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FBE7FDFFFBEB" box="[480,624,1133,1147]" gridcol="1" gridrow="1" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FBE7FE62FBEB" box="[480,493,1133,1147]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFBE7FCA5FBEB" box="[658,810,1133,1147]" gridcol="2" gridrow="1" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BFBE7FD10FBEB" box="[658,671,1133,1147]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4FBE7FC45FBEB" box="[845,970,1133,1147]" gridcol="3" gridrow="1" pageId="6" pageNumber="7">429 ± 30</td>
|
||
<td id="0A5AF26AD13D001CFC77FBE7FB14FBEB" box="[1006,1179,1133,1147]" gridcol="4" gridrow="1" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFBE7FA8CFBEB" box="[1223,1283,1133,1147]" gridcol="5" gridrow="1" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FBE7FA1CFBEB" box="[1313,1427,1133,1147]" gridcol="6" gridrow="1" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFB0EFA37FB02" box="[116,1464,1156,1170]" gridrow="2" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFB0EFE39FB02" box="[116,438,1156,1170]" gridcol="0" gridrow="2" pageId="6" pageNumber="7">
|
||
vincaminoreine (
|
||
<emphasis id="C5CF4546D13DFFE5FF6CFB0EFF70FB02" bold="true" box="[245,255,1156,1170]" pageId="6" pageNumber="7">2</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FB0EFDFFFB02" box="[480,624,1156,1170]" gridcol="1" gridrow="2" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FB0EFE62FB02" box="[480,493,1156,1170]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFB0EFCA5FB02" box="[658,810,1156,1170]" gridcol="2" gridrow="2" pageId="6" pageNumber="7">8.71 ± 0.49</td>
|
||
<td id="0A5AF26AD13D001CFCD4FB0EFC45FB02" box="[845,970,1156,1170]" gridcol="3" gridrow="2" pageId="6" pageNumber="7">408 ± 60</td>
|
||
<td id="0A5AF26AD13D001CFC77FB0EFB14FB02" box="[1006,1179,1156,1170]" gridcol="4" gridrow="2" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFB0EFA8CFB02" box="[1223,1283,1156,1170]" gridcol="5" gridrow="2" pageId="6" pageNumber="7">0.262</td>
|
||
<td id="0A5AF26AD13D001CFAB8FB0EFA1CFB02" box="[1313,1427,1156,1170]" gridcol="6" gridrow="2" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFB11FA37FB39" box="[116,1464,1179,1193]" gridrow="3" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFB11FE39FB39" box="[116,438,1179,1193]" gridcol="0" gridrow="3" pageId="6" pageNumber="7">
|
||
eburnamonine (
|
||
<emphasis id="C5CF4546D13DFFE5FF74FB11FF78FB39" bold="true" box="[237,247,1179,1193]" pageId="6" pageNumber="7">3</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FB11FDFFFB39" box="[480,624,1179,1193]" gridcol="1" gridrow="3" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FB11FE62FB39" box="[480,493,1179,1193]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFB11FCA5FB39" box="[658,810,1179,1193]" gridcol="2" gridrow="3" pageId="6" pageNumber="7">93.49 ± 15.90</td>
|
||
<td id="0A5AF26AD13D001CFCD4FB11FC45FB39" box="[845,970,1179,1193]" gridcol="3" gridrow="3" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FB11FB14FB39" box="[1006,1179,1179,1193]" gridcol="4" gridrow="3" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFB11FA8CFB39" box="[1223,1283,1179,1193]" gridcol="5" gridrow="3" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FB11FA1CFB39" box="[1313,1427,1179,1193]" gridcol="6" gridrow="3" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFB3BFA37FB50" box="[116,1464,1201,1216]" gridrow="4" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFB3BFE39FB50" box="[116,438,1201,1216]" gridcol="0" gridrow="4" pageId="6" pageNumber="7">
|
||
minovine (
|
||
<emphasis id="C5CF4546D13DFFE5FF5FFB3BFF5FFB2F" bold="true" box="[198,208,1201,1215]" pageId="6" pageNumber="7">4</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FB3BFDFFFB50" box="[480,624,1201,1216]" gridcol="1" gridrow="4" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FB38FE62FB50" box="[480,493,1202,1216]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFB3BFCA5FB50" box="[658,810,1201,1216]" gridcol="2" gridrow="4" pageId="6" pageNumber="7">26.32 ± 2.52</td>
|
||
<td id="0A5AF26AD13D001CFCD4FB3BFC45FB50" box="[845,970,1201,1216]" gridcol="3" gridrow="4" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FB3BFB14FB50" box="[1006,1179,1201,1216]" gridcol="4" gridrow="4" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFB3BFA8CFB50" box="[1223,1283,1201,1216]" gridcol="5" gridrow="4" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FB3BFA1CFB50" box="[1313,1427,1201,1216]" gridcol="6" gridrow="4" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFB42FA37FB47" box="[116,1464,1224,1239]" gridrow="5" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFB42FE39FB47" box="[116,438,1224,1239]" gridcol="0" gridrow="5" pageId="6" pageNumber="7">
|
||
16-methoxyminovine (
|
||
<emphasis id="C5CF4546D13DFFE5FEB9FB42FEA5FB46" bold="true" box="[288,298,1224,1238]" pageId="6" pageNumber="7">5</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FB42FDFFFB47" box="[480,624,1224,1239]" gridcol="1" gridrow="5" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FB43FE62FB47" box="[480,493,1225,1239]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFB42FCA5FB47" box="[658,810,1224,1239]" gridcol="2" gridrow="5" pageId="6" pageNumber="7">25.01 ± 3.27</td>
|
||
<td id="0A5AF26AD13D001CFCD4FB42FC45FB47" box="[845,970,1224,1239]" gridcol="3" gridrow="5" pageId="6" pageNumber="7">n.t.</td>
|
||
<td id="0A5AF26AD13D001CFC77FB42FB14FB47" box="[1006,1179,1224,1239]" gridcol="4" gridrow="5" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFB42FA8CFB47" box="[1223,1283,1224,1239]" gridcol="5" gridrow="5" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FB42FA1CFB47" box="[1313,1427,1224,1239]" gridcol="6" gridrow="5" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFB55FA37FB7E" box="[116,1464,1247,1262]" gridrow="6" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFB55FE39FB7E" box="[116,438,1247,1262]" gridcol="0" gridrow="6" pageId="6" pageNumber="7">
|
||
vincatine (
|
||
<emphasis id="C5CF4546D13DFFE5FF5CFB55FF40FB7D" bold="true" box="[197,207,1247,1261]" pageId="6" pageNumber="7">6</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FB55FDFFFB7E" box="[480,624,1247,1262]" gridcol="1" gridrow="6" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FB6AFE62FB7E" box="[480,493,1248,1262]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFB55FCA5FB7E" box="[658,810,1247,1262]" gridcol="2" gridrow="6" pageId="6" pageNumber="7">43.47 ± 3.30</td>
|
||
<td id="0A5AF26AD13D001CFCD4FB55FC45FB7E" box="[845,970,1247,1262]" gridcol="3" gridrow="6" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FB55FB14FB7E" box="[1006,1179,1247,1262]" gridcol="4" gridrow="6" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFB55FA8CFB7E" box="[1223,1283,1247,1262]" gridcol="5" gridrow="6" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FB55FA1CFB7E" box="[1313,1427,1247,1262]" gridcol="6" gridrow="6" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFB7CFA37FA94" box="[116,1464,1270,1284]" gridrow="7" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFB7CFE39FA94" box="[116,438,1270,1284]" gridcol="0" gridrow="7" pageId="6" pageNumber="7">
|
||
minovincine (
|
||
<emphasis id="C5CF4546D13DFFE5FF44FB7CFF68FA94" bold="true" box="[221,231,1270,1284]" pageId="6" pageNumber="7">7</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FB7CFDFFFA94" box="[480,624,1270,1284]" gridcol="1" gridrow="7" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FB7CFE62FA94" box="[480,493,1270,1284]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFB7CFCA5FA94" box="[658,810,1270,1284]" gridcol="2" gridrow="7" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BFB7CFD10FA94" box="[658,671,1270,1284]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4FB7CFC45FA94" box="[845,970,1270,1284]" gridcol="3" gridrow="7" pageId="6" pageNumber="7">301 ± 15</td>
|
||
<td id="0A5AF26AD13D001CFC77FB7CFB14FA94" box="[1006,1179,1270,1284]" gridcol="4" gridrow="7" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFB7CFA8CFA94" box="[1223,1283,1270,1284]" gridcol="5" gridrow="7" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FB7CFA1CFA94" box="[1313,1427,1270,1284]" gridcol="6" gridrow="7" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFA87FA37FA8B" box="[116,1464,1293,1307]" gridrow="8" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFA87FE39FA8B" box="[116,438,1293,1307]" gridcol="0" gridrow="8" pageId="6" pageNumber="7">
|
||
16-methoxyminovincine (
|
||
<emphasis id="C5CF4546D13DFFE5FEAEFA87FECEFA8B" bold="true" box="[311,321,1293,1307]" pageId="6" pageNumber="7">8</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FA87FDFFFA8B" box="[480,624,1293,1307]" gridcol="1" gridrow="8" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FA87FE62FA8B" box="[480,493,1293,1307]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFA87FCA5FA8B" box="[658,810,1293,1307]" gridcol="2" gridrow="8" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BFA87FD10FA8B" box="[658,671,1293,1307]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4FA87FC45FA8B" box="[845,970,1293,1307]" gridcol="3" gridrow="8" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FA87FB14FA8B" box="[1006,1179,1293,1307]" gridcol="4" gridrow="8" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFA87FA8CFA8B" box="[1223,1283,1293,1307]" gridcol="5" gridrow="8" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FA87FA1CFA8B" box="[1313,1427,1293,1307]" gridcol="6" gridrow="8" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFAAEFA37FAA2" box="[116,1464,1316,1330]" gridrow="9" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFAAEFE39FAA2" box="[116,438,1316,1330]" gridcol="0" gridrow="9" pageId="6" pageNumber="7">
|
||
vincaminorudeine (
|
||
<emphasis id="C5CF4546D13DFFE5FE91FAAEFE9DFAA2" bold="true" box="[264,274,1316,1330]" pageId="6" pageNumber="7">9</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FAAEFDFFFAA2" box="[480,624,1316,1330]" gridcol="1" gridrow="9" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FAAEFE62FAA2" box="[480,493,1316,1330]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFAAEFCA5FAA2" box="[658,810,1316,1330]" gridcol="2" gridrow="9" pageId="6" pageNumber="7">84.91 ± 2.98</td>
|
||
<td id="0A5AF26AD13D001CFCD4FAAEFC45FAA2" box="[845,970,1316,1330]" gridcol="3" gridrow="9" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FAAEFB14FAA2" box="[1006,1179,1316,1330]" gridcol="4" gridrow="9" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFAAEFA8CFAA2" box="[1223,1283,1316,1330]" gridcol="5" gridrow="9" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FAAEFA1CFAA2" box="[1313,1427,1316,1330]" gridcol="6" gridrow="9" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFAB1FA37FAD9" box="[116,1464,1339,1353]" gridrow="10" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFAB1FE39FAD9" box="[116,438,1339,1353]" gridcol="0" gridrow="10" pageId="6" pageNumber="7">
|
||
demethoxyalstonamide (
|
||
<emphasis id="C5CF4546D13DFFE5FEB7FAB1FECDFAD9" bold="true" box="[302,322,1339,1353]" pageId="6" pageNumber="7">10</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FAB1FDFFFAD9" box="[480,624,1339,1353]" gridcol="1" gridrow="10" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FAB1FE62FAD9" box="[480,493,1339,1353]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFAB1FCA5FAD9" box="[658,810,1339,1353]" gridcol="2" gridrow="10" pageId="6" pageNumber="7">56.38 ± 2.58</td>
|
||
<td id="0A5AF26AD13D001CFCD4FAB1FC45FAD9" box="[845,970,1339,1353]" gridcol="3" gridrow="10" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FAB1FB14FAD9" box="[1006,1179,1339,1353]" gridcol="4" gridrow="10" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFAB1FA8CFAD9" box="[1223,1283,1339,1353]" gridcol="5" gridrow="10" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FAB1FA1CFAD9" box="[1313,1427,1339,1353]" gridcol="6" gridrow="10" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFADBFA37FAF0" box="[116,1464,1361,1376]" gridrow="11" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFADBFE39FAF0" box="[116,438,1361,1376]" gridcol="0" gridrow="11" pageId="6" pageNumber="7">
|
||
vincorine (
|
||
<emphasis id="C5CF4546D13DFFE5FF5FFADBFF55FACF" bold="true" box="[198,218,1361,1375]" pageId="6" pageNumber="7">11</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FADBFDFFFAF0" box="[480,624,1361,1376]" gridcol="1" gridrow="11" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FAD8FE62FAF0" box="[480,493,1362,1376]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFADBFCA5FAF0" box="[658,810,1361,1376]" gridcol="2" gridrow="11" pageId="6" pageNumber="7">9.75 ± 0.45</td>
|
||
<td id="0A5AF26AD13D001CFCD4FADBFC45FAF0" box="[845,970,1361,1376]" gridcol="3" gridrow="11" pageId="6" pageNumber="7">n.t.</td>
|
||
<td id="0A5AF26AD13D001CFC77FADBFB14FAF0" box="[1006,1179,1361,1376]" gridcol="4" gridrow="11" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFADBFA8CFAF0" box="[1223,1283,1361,1376]" gridcol="5" gridrow="11" pageId="6" pageNumber="7">0.022</td>
|
||
<td id="0A5AF26AD13D001CFAB8FADBFA1CFAF0" box="[1313,1427,1361,1376]" gridcol="6" gridrow="11" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFAE2FA37FAE7" box="[116,1464,1384,1399]" gridrow="12" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFAE2FE39FAE7" box="[116,438,1384,1399]" gridcol="0" gridrow="12" pageId="6" pageNumber="7">
|
||
minovincinine (
|
||
<emphasis id="C5CF4546D13DFFE5FF75FAE2FE8FFAE6" bold="true" box="[236,256,1384,1398]" pageId="6" pageNumber="7">12</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FAE2FDFFFAE7" box="[480,624,1384,1399]" gridcol="1" gridrow="12" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FAE3FE62FAE7" box="[480,493,1385,1399]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFAE2FCA5FAE7" box="[658,810,1384,1399]" gridcol="2" gridrow="12" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BFAE3FD10FAE7" box="[658,671,1385,1399]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4FAE2FC45FAE7" box="[845,970,1384,1399]" gridcol="3" gridrow="12" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FAE2FB14FAE7" box="[1006,1179,1384,1399]" gridcol="4" gridrow="12" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFAE2FA8CFAE7" box="[1223,1283,1384,1399]" gridcol="5" gridrow="12" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FAE2FA1CFAE7" box="[1313,1427,1384,1399]" gridcol="6" gridrow="12" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFAF5FA37FA1E" box="[116,1464,1407,1422]" gridrow="13" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFAF5FE39FA1E" box="[116,438,1407,1422]" gridcol="0" gridrow="13" pageId="6" pageNumber="7">
|
||
aspidospermidine (
|
||
<emphasis id="C5CF4546D13DFFE5FE9DFAF5FE97FA1D" bold="true" box="[260,280,1407,1421]" pageId="6" pageNumber="7">13</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FAF5FDFFFA1E" box="[480,624,1407,1422]" gridcol="1" gridrow="13" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FA0AFE62FA1E" box="[480,493,1408,1422]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFAF5FCA5FA1E" box="[658,810,1407,1422]" gridcol="2" gridrow="13" pageId="6" pageNumber="7">33.60 ± 1.52</td>
|
||
<td id="0A5AF26AD13D001CFCD4FAF5FC45FA1E" box="[845,970,1407,1422]" gridcol="3" gridrow="13" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FAF5FB14FA1E" box="[1006,1179,1407,1422]" gridcol="4" gridrow="13" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFAF5FA8CFA1E" box="[1223,1283,1407,1422]" gridcol="5" gridrow="13" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FAF5FA1CFA1E" box="[1313,1427,1407,1422]" gridcol="6" gridrow="13" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFA1CFA37FA34" box="[116,1464,1430,1444]" gridrow="14" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFA1CFE39FA34" box="[116,438,1430,1444]" gridcol="0" gridrow="14" pageId="6" pageNumber="7">
|
||
19-oxoeburnamonine (
|
||
<emphasis id="C5CF4546D13DFFE5FEB9FA1CFEBBFA34" bold="true" box="[288,308,1430,1444]" pageId="6" pageNumber="7">14</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FA1CFDFFFA34" box="[480,624,1430,1444]" gridcol="1" gridrow="14" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FA1CFE62FA34" box="[480,493,1430,1444]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFA1CFCA5FA34" box="[658,810,1430,1444]" gridcol="2" gridrow="14" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BFA1CFD10FA34" box="[658,671,1430,1444]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4FA1CFC45FA34" box="[845,970,1430,1444]" gridcol="3" gridrow="14" pageId="6" pageNumber="7">n.t.</td>
|
||
<td id="0A5AF26AD13D001CFC77FA1CFB14FA34" box="[1006,1179,1430,1444]" gridcol="4" gridrow="14" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFA1CFA8CFA34" box="[1223,1283,1430,1444]" gridcol="5" gridrow="14" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FA1CFA1CFA34" box="[1313,1427,1430,1444]" gridcol="6" gridrow="14" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFA27FA37FA2B" box="[116,1464,1453,1467]" gridrow="15" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFA27FE39FA2B" box="[116,438,1453,1467]" gridcol="0" gridrow="15" pageId="6" pageNumber="7">
|
||
akuammicine (
|
||
<emphasis id="C5CF4546D13DFFE5FF7CFA27FF76FA2B" bold="true" box="[229,249,1453,1467]" pageId="6" pageNumber="7">15</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FA27FDFFFA2B" box="[480,624,1453,1467]" gridcol="1" gridrow="15" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FA27FE62FA2B" box="[480,493,1453,1467]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFA27FCA5FA2B" box="[658,810,1453,1467]" gridcol="2" gridrow="15" pageId="6" pageNumber="7">38.17 ± 0.84</td>
|
||
<td id="0A5AF26AD13D001CFCD4FA27FC45FA2B" box="[845,970,1453,1467]" gridcol="3" gridrow="15" pageId="6" pageNumber="7">n.t.</td>
|
||
<td id="0A5AF26AD13D001CFC77FA27FB14FA2B" box="[1006,1179,1453,1467]" gridcol="4" gridrow="15" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFA27FA8CFA2B" box="[1223,1283,1453,1467]" gridcol="5" gridrow="15" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FA27FA1CFA2B" box="[1313,1427,1453,1467]" gridcol="6" gridrow="15" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFA4EFA37FA42" box="[116,1464,1476,1490]" gridrow="16" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFA4EFE39FA42" box="[116,438,1476,1490]" gridcol="0" gridrow="16" pageId="6" pageNumber="7">
|
||
tubotaiwine (
|
||
<emphasis id="C5CF4546D13DFFE5FF43FA4EFF61FA42" bold="true" box="[218,238,1476,1490]" pageId="6" pageNumber="7">16</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FA4EFDFFFA42" box="[480,624,1476,1490]" gridcol="1" gridrow="16" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FA4EFE62FA42" box="[480,493,1476,1490]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFA4EFCA5FA42" box="[658,810,1476,1490]" gridcol="2" gridrow="16" pageId="6" pageNumber="7">11.70 ± 0.11</td>
|
||
<td id="0A5AF26AD13D001CFCD4FA4EFC45FA42" box="[845,970,1476,1490]" gridcol="3" gridrow="16" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FA4EFB14FA42" box="[1006,1179,1476,1490]" gridcol="4" gridrow="16" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFA4EFA8CFA42" box="[1223,1283,1476,1490]" gridcol="5" gridrow="16" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FA4EFA1CFA42" box="[1313,1427,1476,1490]" gridcol="6" gridrow="16" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFA51FA37FA79" box="[116,1464,1499,1513]" gridrow="17" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFA51FE39FA79" box="[116,438,1499,1513]" gridcol="0" gridrow="17" pageId="6" pageNumber="7">
|
||
raucubainine (
|
||
<emphasis id="C5CF4546D13DFFE5FF7BFA51FF79FA79" bold="true" box="[226,246,1499,1513]" pageId="6" pageNumber="7">17</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FA51FDFFFA79" box="[480,624,1499,1513]" gridcol="1" gridrow="17" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FA51FE62FA79" box="[480,493,1499,1513]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFA51FCA5FA79" box="[658,810,1499,1513]" gridcol="2" gridrow="17" pageId="6" pageNumber="7">93.96 ± 6.80</td>
|
||
<td id="0A5AF26AD13D001CFCD4FA51FC45FA79" box="[845,970,1499,1513]" gridcol="3" gridrow="17" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FCD4FA51FCD5FA79" box="[845,858,1499,1513]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
500
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFC77FA51FB14FA79" box="[1006,1179,1499,1513]" gridcol="4" gridrow="17" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFA51FA8CFA79" box="[1223,1283,1499,1513]" gridcol="5" gridrow="17" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FA51FA1CFA79" box="[1313,1427,1499,1513]" gridcol="6" gridrow="17" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDFA7BFA37F990" box="[116,1464,1521,1536]" gridrow="18" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDFA7BFE39F990" box="[116,438,1521,1536]" gridcol="0" gridrow="18" pageId="6" pageNumber="7">
|
||
aspidofractinine (
|
||
<emphasis id="C5CF4546D13DFFE5FF60FA7BFE82FA6F" bold="true" box="[249,269,1521,1535]" pageId="6" pageNumber="7">18</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79FA7BFDFFF990" box="[480,624,1521,1536]" gridcol="1" gridrow="18" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79FA78FE62F990" box="[480,493,1522,1536]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BFA7BFCA5F990" box="[658,810,1521,1536]" gridcol="2" gridrow="18" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BFA78FD10F990" box="[658,671,1522,1536]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4FA7BFC45F990" box="[845,970,1521,1536]" gridcol="3" gridrow="18" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77FA7BFB14F990" box="[1006,1179,1521,1536]" gridcol="4" gridrow="18" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EFA7BFA8CF990" box="[1223,1283,1521,1536]" gridcol="5" gridrow="18" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8FA7BFA1CF990" box="[1313,1427,1521,1536]" gridcol="6" gridrow="18" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF982FA37F987" box="[116,1464,1544,1559]" gridrow="19" pageId="6" pageNumber="7">
|
||
<th id="0A5AF26AD13D001CFFEDF982FE39F987" box="[116,438,1544,1559]" gridcol="0" gridrow="19" pageId="6" pageNumber="7">
|
||
2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1
|
||
<emphasis id="C5CF4546D13DFFE5FE3DF982FE39F987" bold="true" box="[420,438,1544,1559]" italics="true" pageId="6" pageNumber="7">H -</emphasis>
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79F982FDFFF987" box="[480,624,1544,1559]" gridcol="1" gridrow="19" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79F983FE62F987" box="[480,493,1545,1559]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BF982FCA5F987" box="[658,810,1544,1559]" gridcol="2" gridrow="19" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BF982FC8BF986" bold="true" box="[658,772,1544,1559]" pageId="6" pageNumber="7">0.650 ± 0.016</emphasis>
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4F982FC45F987" box="[845,970,1544,1559]" gridcol="3" gridrow="19" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FCD4F982FC0DF986" bold="true" box="[845,898,1544,1559]" pageId="6" pageNumber="7">58 ± 4</emphasis>
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFC77F982FB14F987" box="[1006,1179,1544,1559]" gridcol="4" gridrow="19" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FC77F982FBD9F986" bold="true" box="[1006,1110,1544,1559]" pageId="6" pageNumber="7">31.43 ± 3.05</emphasis>
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFB5EF982FA8CF987" box="[1223,1283,1544,1559]" gridcol="5" gridrow="19" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FB5EF982FA8CF986" bold="true" box="[1223,1283,1544,1559]" pageId="6" pageNumber="7">¡0.164</emphasis>
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFAB8F982FA37F987" box="[1313,1464,1544,1559]" colspan="2" colspanRight="1" gridcol="6" gridrow="19" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FAB8F982FA37F986" bold="true" box="[1313,1464,1544,1559]" pageId="6" pageNumber="7">15.7 ± 1.3 (CNSþ)</emphasis>
|
||
</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF995FA37F9BD" box="[116,1464,1567,1581]" gridrow="20" pageId="6" pageNumber="7">
|
||
<th id="0A5AF26AD13D001CFFEDF995FA37F9BD" box="[116,1464,1567,1581]" colspan="8" colspanRight="7" gridcol="0" gridrow="20" pageId="6" pageNumber="7">
|
||
indole (
|
||
<emphasis id="C5CF4546D13DFFE5FF26F995FF5CF9BD" bold="true" box="[191,211,1567,1581]" pageId="6" pageNumber="7">19</emphasis>
|
||
)
|
||
</th>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF9BCFA37F9D4" box="[116,1464,1590,1604]" gridrow="21" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDF9BCFE39F9D4" box="[116,438,1590,1604]" gridcol="0" gridrow="21" pageId="6" pageNumber="7">
|
||
dihydrovindolinine (
|
||
<emphasis id="C5CF4546D13DFFE5FE89F9BCFEABF9D4" bold="true" box="[272,292,1590,1604]" pageId="6" pageNumber="7">20</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79F9BCFDFFF9D4" box="[480,624,1590,1604]" gridcol="1" gridrow="21" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79F9BCFE62F9D4" box="[480,493,1590,1604]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BF9BCFCA5F9D4" box="[658,810,1590,1604]" gridcol="2" gridrow="21" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BF9BCFD10F9D4" box="[658,671,1590,1604]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4F9BCFC45F9D4" box="[845,970,1590,1604]" gridcol="3" gridrow="21" pageId="6" pageNumber="7">n.d.</td>
|
||
<td id="0A5AF26AD13D001CFC77F9BCFB14F9D4" box="[1006,1179,1590,1604]" gridcol="4" gridrow="21" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EF9BCFA8CF9D4" box="[1223,1283,1590,1604]" gridcol="5" gridrow="21" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8F9BCFA1CF9D4" box="[1313,1427,1590,1604]" gridcol="6" gridrow="21" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF9C7FA37F9CB" box="[116,1464,1613,1627]" gridrow="22" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDF9C7FE39F9CB" box="[116,438,1613,1627]" gridcol="0" gridrow="22" pageId="6" pageNumber="7">
|
||
strictamine (
|
||
<emphasis id="C5CF4546D13DFFE5FF4DF9C7FF67F9CB" bold="true" box="[212,232,1613,1627]" pageId="6" pageNumber="7">21</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79F9C7FDFFF9CB" box="[480,624,1613,1627]" gridcol="1" gridrow="22" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79F9C7FE62F9CB" box="[480,493,1613,1627]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BF9C7FCA5F9CB" box="[658,810,1613,1627]" gridcol="2" gridrow="22" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BF9C7FD10F9CB" box="[658,671,1613,1627]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4F9C7FC45F9CB" box="[845,970,1613,1627]" gridcol="3" gridrow="22" pageId="6" pageNumber="7">190 ± 11</td>
|
||
<td id="0A5AF26AD13D001CFC77F9C7FB14F9CB" box="[1006,1179,1613,1627]" gridcol="4" gridrow="22" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EF9C7FA8CF9CB" box="[1223,1283,1613,1627]" gridcol="5" gridrow="22" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8F9C7FA1CF9CB" box="[1313,1427,1613,1627]" gridcol="6" gridrow="22" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF9EEFA37F9E2" box="[116,1464,1636,1650]" gridrow="23" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDF9EEFE39F9E2" box="[116,438,1636,1650]" gridcol="0" gridrow="23" pageId="6" pageNumber="7">
|
||
5-oxoaspidofractinine (
|
||
<emphasis id="C5CF4546D13DFFE5FEBAF9EEFEB8F9E2" bold="true" box="[291,311,1636,1650]" pageId="6" pageNumber="7">22</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79F9EEFDFFF9E2" box="[480,624,1636,1650]" gridcol="1" gridrow="23" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79F9EEFE62F9E2" box="[480,493,1636,1650]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BF9EEFCA5F9E2" box="[658,810,1636,1650]" gridcol="2" gridrow="23" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BF9EEFD10F9E2" box="[658,671,1636,1650]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4F9EEFC45F9E2" box="[845,970,1636,1650]" gridcol="3" gridrow="23" pageId="6" pageNumber="7">n.t.</td>
|
||
<td id="0A5AF26AD13D001CFC77F9EEFB14F9E2" box="[1006,1179,1636,1650]" gridcol="4" gridrow="23" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EF9EEFA8CF9E2" box="[1223,1283,1636,1650]" gridcol="5" gridrow="23" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8F9EEFA1CF9E2" box="[1313,1427,1636,1650]" gridcol="6" gridrow="23" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF9F0FA37F919" box="[116,1464,1658,1673]" gridrow="24" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDF9F0FE39F919" box="[116,438,1658,1673]" gridcol="0" gridrow="24" pageId="6" pageNumber="7">
|
||
raucubaine (
|
||
<emphasis id="C5CF4546D13DFFE5FF4DF9F0FF67F918" bold="true" box="[212,232,1658,1672]" pageId="6" pageNumber="7">23</emphasis>
|
||
)
|
||
</th>
|
||
<td id="0A5AF26AD13D001CFE79F9F0FDFFF919" box="[480,624,1658,1673]" gridcol="1" gridrow="24" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FE79F9F1FE62F919" box="[480,493,1659,1673]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFD0BF9F0FCA5F919" box="[658,810,1658,1673]" gridcol="2" gridrow="24" pageId="6" pageNumber="7">
|
||
<emphasis id="C5CF4546D13DFFE5FD0BF9F1FD10F919" box="[658,671,1659,1673]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
100
|
||
</td>
|
||
<td id="0A5AF26AD13D001CFCD4F9F0FC45F919" box="[845,970,1658,1673]" gridcol="3" gridrow="24" pageId="6" pageNumber="7">n.t.</td>
|
||
<td id="0A5AF26AD13D001CFC77F9F0FB14F919" box="[1006,1179,1658,1673]" gridcol="4" gridrow="24" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EF9F0FA8CF919" box="[1223,1283,1658,1673]" gridcol="5" gridrow="24" pageId="6" pageNumber="7">n.c.</td>
|
||
<td id="0A5AF26AD13D001CFAB8F9F0FA1CF919" box="[1313,1427,1658,1673]" gridcol="6" gridrow="24" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF907FA37F930" box="[116,1464,1677,1696]" gridrow="25" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDF907FE39F930" box="[116,438,1677,1696]" gridcol="0" gridrow="25" pageId="6" pageNumber="7">galanthamine e</th>
|
||
<td id="0A5AF26AD13D001CFE79F907FDFFF930" box="[480,624,1677,1696]" gridcol="1" gridrow="25" pageId="6" pageNumber="7">1.72 ± 0.12</td>
|
||
<td id="0A5AF26AD13D001CFD0BF907FCA5F930" box="[658,810,1677,1696]" gridcol="2" gridrow="25" pageId="6" pageNumber="7">42 ± 1</td>
|
||
<td id="0A5AF26AD13D001CFCD4F907FC45F930" box="[845,970,1677,1696]" gridcol="3" gridrow="25" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFC77F907FB14F930" box="[1006,1179,1677,1696]" gridcol="4" gridrow="25" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EF907FA8CF930" box="[1223,1283,1677,1696]" gridcol="5" gridrow="25" pageId="6" pageNumber="7">0.047</td>
|
||
<td id="0A5AF26AD13D001CFAB8F907FA1CF930" box="[1313,1427,1677,1696]" gridcol="6" gridrow="25" pageId="6" pageNumber="7">
|
||
5.1 (CNS)
|
||
<emphasis id="C5CF4546D13DFFE5FAE1F907FAF3F907" bold="true" box="[1400,1404,1677,1687]" italics="true" pageId="6" pageNumber="7">f</emphasis>
|
||
+
|
||
</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF92FFA37F927" box="[116,1464,1701,1719]" gridrow="26" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDF92FFE39F927" box="[116,438,1701,1719]" gridcol="0" gridrow="26" pageId="6" pageNumber="7">eserine e</th>
|
||
<td id="0A5AF26AD13D001CFE79F92FFDFFF927" box="[480,624,1701,1719]" gridcol="1" gridrow="26" pageId="6" pageNumber="7">0.063 ± 0.005</td>
|
||
<td id="0A5AF26AD13D001CFD0BF92FFCA5F927" box="[658,810,1701,1719]" gridcol="2" gridrow="26" pageId="6" pageNumber="7">0.13 ± 0.01</td>
|
||
<td id="0A5AF26AD13D001CFCD4F92FFC45F927" box="[845,970,1701,1719]" gridcol="3" gridrow="26" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFC77F92FFB14F927" box="[1006,1179,1701,1719]" gridcol="4" gridrow="26" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EF92FFA8CF927" box="[1223,1283,1701,1719]" gridcol="5" gridrow="26" pageId="6" pageNumber="7">0.177</td>
|
||
<td id="0A5AF26AD13D001CFAB8F92FFA1CF927" box="[1313,1427,1701,1719]" gridcol="6" gridrow="26" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF931FA37F95D" box="[116,1464,1723,1741]" gridrow="27" pageId="6" pageNumber="7" rowspan-7="1">
|
||
<th id="0A5AF26AD13D001CFFEDF931FE39F95D" box="[116,438,1723,1741]" gridcol="0" gridrow="27" pageId="6" pageNumber="7">berberine e</th>
|
||
<td id="0A5AF26AD13D001CFE79F931FDFFF95D" box="[480,624,1723,1741]" gridcol="1" gridrow="27" pageId="6" pageNumber="7">0.72 ± 0.11</td>
|
||
<td id="0A5AF26AD13D001CFD0BF931FCA5F95D" box="[658,810,1723,1741]" gridcol="2" gridrow="27" pageId="6" pageNumber="7">31 ± 4</td>
|
||
<td id="0A5AF26AD13D001CFCD4F931FC45F95D" box="[845,970,1723,1741]" gridcol="3" gridrow="27" pageId="6" pageNumber="7">142 ± 21</td>
|
||
<td id="0A5AF26AD13D001CFC77F931FB14F95D" box="[1006,1179,1723,1741]" gridcol="4" gridrow="27" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EF931FA8CF95D" box="[1223,1283,1723,1741]" gridcol="5" gridrow="27" pageId="6" pageNumber="7">0.420</td>
|
||
<td id="0A5AF26AD13D001CFAB8F931FA1CF95D" box="[1313,1427,1723,1741]" gridcol="6" gridrow="27" pageId="6" pageNumber="7">–</td>
|
||
</tr>
|
||
<tr id="498B9B16D13D001CFFEDF958FA37F974" box="[116,1464,1746,1764]" gridrow="28" pageId="6" pageNumber="7">
|
||
<th id="0A5AF26AD13D001CFFEDF958FE39F974" box="[116,438,1746,1764]" gridcol="0" gridrow="28" pageId="6" pageNumber="7">chlorothiazide e</th>
|
||
<td id="0A5AF26AD13D001CFE79F958FDFFF974" box="[480,624,1746,1764]" gridcol="1" gridrow="28" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFD0BF958FCA5F974" box="[658,810,1746,1764]" gridcol="2" gridrow="28" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFCD4F958FC45F974" box="[845,970,1746,1764]" gridcol="3" gridrow="28" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFC77F958FB14F974" box="[1006,1179,1746,1764]" gridcol="4" gridrow="28" pageId="6" pageNumber="7">–</td>
|
||
<td id="0A5AF26AD13D001CFB5EF958FA8CF974" box="[1223,1283,1746,1764]" gridcol="5" gridrow="28" pageId="6" pageNumber="7">0.418</td>
|
||
<td id="0A5AF26AD13D001CFAB8F958FA1CF974" box="[1313,1427,1746,1764]" gridcol="6" gridrow="28" pageId="6" pageNumber="7">1.1 ± 0.5 (CNS</td>
|
||
<td id="0A5AF26AD13D001CFA38F958FA37F974" box="[1441,1464,1746,1764]" gridcol="7" gridrow="28" pageId="6" pageNumber="7">)</td>
|
||
</tr>
|
||
</table>
|
||
</paragraph>
|
||
<tableNote id="0A5D98DAD13DFFE5FFEAF97FFDD7F82D" pageId="6" pageNumber="7" targetBox="[116,1464,1071,1764]" targetPageId="6">
|
||
<paragraph id="F7049954D13DFFE5FFEAF97FFF37F8B4" blockId="6.[100,1487,1781,1981]" pageId="6" pageNumber="7">
|
||
<superScript id="00CE341CD13DFFE5FFEAF97FFFF5F891" attach="right" box="[115,122,1781,1793]" fontSize="5" pageId="6" pageNumber="7">a</superScript>
|
||
Compound concentration required to decrease enzyme activity by 50%; the values are the mean SEM of three independent measurements, each performed in ± triplicate.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13DFFE5FFEAF8A2FE55F8AD" blockId="6.[100,1487,1781,1981]" box="[115,474,1832,1855]" pageId="6" pageNumber="7">
|
||
<superScript id="00CE341CD13DFFE5FFEAF8A2FFF4F8A4" attach="left" box="[115,123,1832,1844]" fontSize="5" pageId="6" pageNumber="7">b</superScript>
|
||
Measured at a concentration of 100 μM.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13DFFE5FFEAF8C8FD81F8C7" blockId="6.[100,1487,1781,1981]" box="[115,526,1858,1879]" pageId="6" pageNumber="7">
|
||
<superScript id="00CE341CD13DFFE5FFEAF8C8FFF5F8DE" attach="left" box="[115,122,1858,1870]" fontSize="5" pageId="6" pageNumber="7">c</superScript>
|
||
calculated at http://www.way2drug.com/geb.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13DFFE5FFEAF8D1FD8EF81A" blockId="6.[100,1487,1781,1981]" pageId="6" pageNumber="7">
|
||
<superScript id="00CE341CD13DFFE5FFEAF8D1FFF4F8F7" attach="right" box="[115,123,1883,1895]" fontSize="5" pageId="6" pageNumber="7">d</superScript>
|
||
CNS(): high BBB permeation predicted with
|
||
<emphasis id="C5CF4546D13DFFE5FD98F8EAFD83F8E0" bold="true" box="[513,524,1888,1904]" italics="true" pageId="6" pageNumber="7">P</emphasis>
|
||
(10
|
||
<superScript id="00CE341CD13DFFE5FDA6F8D1FDC8F8F7" attach="right" box="[575,583,1883,1895]" fontSize="5" pageId="6" pageNumber="7">6</superScript>
|
||
cm s
|
||
<superScript id="00CE341CD13DFFE5FDE2F8D1FD0CF8F7" attach="right" box="[635,643,1883,1895]" fontSize="5" pageId="6" pageNumber="7">1</superScript>
|
||
)
|
||
<emphasis id="C5CF4546D13DFFE5FD17F8EAFD12F8E1" box="[654,669,1888,1905]" italics="true" pageId="6" pageNumber="7">></emphasis>
|
||
4.0, CNS(): low BBB permeation predicted with
|
||
<emphasis id="C5CF4546D13DFFE5FBA2F8EAFBC9F8E0" bold="true" box="[1083,1094,1888,1904]" italics="true" pageId="6" pageNumber="7">P</emphasis>
|
||
(10
|
||
<superScript id="00CE341CD13DFFE5FBE1F8D1FB0FF8F7" attach="right" box="[1144,1152,1883,1895]" fontSize="5" pageId="6" pageNumber="7">6</superScript>
|
||
cm s
|
||
<superScript id="00CE341CD13DFFE5FB2DF8D1FB33F8F7" attach="right" box="[1204,1212,1883,1895]" fontSize="5" pageId="6" pageNumber="7">1</superScript>
|
||
)
|
||
<emphasis id="C5CF4546D13DFFE5FB5EF8EAFB59F8E1" box="[1223,1238,1888,1905]" italics="true" pageId="6" pageNumber="7"><</emphasis>
|
||
2.0, CNS(): BBB permeation +
|
||
<subScript id="6B3F9B11D13DFFE5FD95F8EDFBC3F8E3" attach="left" box="[524,1100,1895,1907]" fontSize="5" pageId="6" pageNumber="7">e e</subScript>
|
||
± uncertain with
|
||
<emphasis id="C5CF4546D13DFFE5FF7FF8F0FF7EF81A" bold="true" box="[230,241,1914,1930]" italics="true" pageId="6" pageNumber="7">P</emphasis>
|
||
(10
|
||
<superScript id="00CE341CD13DFFE5FEBFF8FEFEA1F810" attach="right" box="[294,302,1908,1920]" fontSize="5" pageId="6" pageNumber="7">6</superScript>
|
||
cm s
|
||
<superScript id="00CE341CD13DFFE5FEFCF8FFFEE2F811" attach="right" box="[357,365,1909,1921]" fontSize="5" pageId="6" pageNumber="7">1</superScript>
|
||
) from 4.0 to 2.0.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13DFFE5FF68F80AFDD7F82D" blockId="6.[100,1487,1781,1981]" pageId="6" pageNumber="7">
|
||
<subScript id="6B3F9B11D13DFFE5FF68F80AFF77F81C" attach="left" box="[241,248,1920,1932]" fontSize="5" pageId="6" pageNumber="7">e</subScript>
|
||
<superScript id="00CE341CD13DFFE5FFEAF804FFF5F80A" attach="right" box="[115,122,1934,1946]" fontSize="5" pageId="6" pageNumber="7">e</superScript>
|
||
Reference compound;
|
||
<emphasis id="C5CF4546D13DFFE5FEA4F804FECDF80A" bold="true" box="[317,322,1934,1946]" italics="true" pageId="6" pageNumber="7">
|
||
<superScript id="00CE341CD13DFFE5FEA4F804FECDF80A" attach="right" box="[317,322,1934,1946]" fontSize="5" pageId="6" pageNumber="7">f</superScript>
|
||
</emphasis>
|
||
Taken from reference (Stavrakov et al., 2017); n.t. stands for not tested due to the isolation of low amount; n.d. stands for not measurable due to a problem with solubility; n.c. stands for not calculated.
|
||
</paragraph>
|
||
</tableNote>
|
||
<caption id="A3C4C9DCD13CFFE4FFFDFD18FDA4FC99" ID-DOI="http://doi.org/10.5281/zenodo.8240074" ID-Zenodo-Dep="8240074" httpUri="https://zenodo.org/record/8240074/files/figure.png" pageId="7" pageNumber="8" startId="7.[100,130,658,675]" targetBox="[107,766,149,630]" targetPageId="7" targetType="figure">
|
||
<paragraph id="F7049954D13CFFE4FFFDFD18FDA4FC99" blockId="7.[100,770,658,777]" pageId="7" pageNumber="8">
|
||
<emphasis id="C5CF4546D13CFFE4FFFDFD18FF12FD33" bold="true" box="[100,157,658,675]" pageId="7" pageNumber="8">Fig. 4.</emphasis>
|
||
Steady state competitive type inhibition of
|
||
<emphasis id="C5CF4546D13CFFE4FD8BFD18FD93FD33" bold="true" box="[530,540,658,675]" italics="true" pageId="7" pageNumber="8">h</emphasis>
|
||
BuChE substrate hydrolysis by active compound
|
||
<emphasis id="C5CF4546D13CFFE4FE81FD26FEA1FD2D" bold="true" box="[280,302,684,701]" pageId="7" pageNumber="8">19</emphasis>
|
||
at different concentrations. Lineweaver Burk plots of initial velocity at increasing substrate concentrations (2.5–10.0 mM) are presented. Lines were derived from a linear regression of the data points. All measurements were made in triplicate and averaged.
|
||
</paragraph>
|
||
</caption>
|
||
<paragraph id="F7049954D13CFFE4FF1DFCC4FDCDFB98" blockId="7.[100,770,818,1340]" pageId="7" pageNumber="8">
|
||
Typical parallel π- π/cation-π stacking can be observed between tacrine and W82 (3.6 Å) (
|
||
<figureCitation id="6F8085D1D13CFFE4FEFCFCE0FE60FCED" box="[357,495,874,893]" captionStart="Fig" captionStartId="8.[100,130,1178,1195]" captionTargetBox="[208,1380,149,1150]" captionTargetId="figure-560@8.[206,1381,148,1151]" captionTargetPageId="8" captionText="Fig. 5. The top-scored docking poses of 19 in hBuChE (A, B; PDB ID: 4BDS) and the crystal structure of tacrine bound to hBuChE (C, D). The ligands are displayed in blue (A) and green (C) for 19 and tacrine, respectively; important amino acid residues responsible for ligand anchoring are shown in grey for hBuChE (A, C). Catalytic triad residues are displayed in yellow (A, C). Important interactions are rendered by black dashed lines; distances are measured in angstroms (Å). The rest of the receptor is displayed in light-grey cartoon conformation (A, C). Figures A and C were created with The PyMOL Molecular Graphics System, Version 2.4.1, Schr¨odinger, LLC. 2D figures (B, D) were generated with Maestro 12.3 (Schr¨odinger Release, Schr¨odinger, LLC, New York, NY, 2020). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)" figureDoi="http://doi.org/10.5281/zenodo.8240076" httpUri="https://zenodo.org/record/8240076/files/figure.png" pageId="7" pageNumber="8">Fig. 5C and D</figureCitation>
|
||
) (Nachon et al., 2013). The amino group of tacrine is anchored to two water molecules, which forms a water-mediated bridge to other residues like D70, S79 and T120 (not shown). From the catalytic triad residues involved in the interaction with tacrine, hydrogen bonding between the aromatic nitrogen
|
||
<emphasis id="C5CF4546D13CFFE4FD27FC50FD42FC7D" bold="true" box="[702,717,986,1005]" italics="true" pageId="7" pageNumber="8">N</emphasis>
|
||
7 and the main chain carbonyl of H438 can be observed.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FF1DFB9BFC8FFAAC" blockId="7.[100,770,818,1340]" pageId="7" pageNumber="8">
|
||
The overlay between
|
||
<emphasis id="C5CF4546D13CFFE4FEC0FB9BFEFDFBB4" bold="true" box="[345,370,1041,1060]" pageId="7" pageNumber="8">19</emphasis>
|
||
and tacrine is displayed in
|
||
<figureCitation id="6F8085D1D13CFFE4FD15FB9BFD4BFBB4" box="[652,708,1041,1060]" captionStart="Fig" captionStartId="9.[100,130,647,664]" captionTargetBox="[108,765,150,618]" captionTargetId="figure-1134@9.[106,767,148,620]" captionTargetPageId="9" captionText="Fig. 6. Overlapped top-scored poses for ligands 19 (blue) and crystal structure of tacrine (green) in the active site of hBuChE (PDB ID: 4BDS). Amino acid residues involved in the interactions with ligands are depicted as either grey or yellow (catalytic triad) lines. The rest of the receptor is displayed in light-grey cartoon conformation. The Figure was created with The PyMOL Molecular Graphics System, Version 2.4.1, Schr¨odinger, LLC. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)" figureDoi="http://doi.org/10.5281/zenodo.8240078" httpUri="https://zenodo.org/record/8240078/files/figure.png" pageId="7" pageNumber="8">Fig. 6</figureCitation>
|
||
. Most importantly, both ligands overlap within their aromatic regions that are implicated in the π- π/cation-π stackings with W82. Similarly, both ligands contact A328, W430 and Y332 by hydrophobic interactions, albeit differently. In the case of tacrine, the aromatic part of the molecule is engaged in these interactions; for
|
||
<emphasis id="C5CF4546D13CFFE4FE3CFB17FE31FB20" bold="true" box="[421,446,1181,1200]" pageId="7" pageNumber="8">19</emphasis>
|
||
, it is the 3-ethylpiperidine moiety that protrudes out to these residues. Besides the mutual amino acid residues involved in the interaction with both
|
||
<emphasis id="C5CF4546D13CFFE4FDB1FB5FFDCEFB78" bold="true" box="[552,577,1237,1256]" pageId="7" pageNumber="8">19</emphasis>
|
||
and tacrine,
|
||
<emphasis id="C5CF4546D13CFFE4FD5DFB5FFD52FB78" bold="true" box="[708,733,1237,1256]" pageId="7" pageNumber="8">19</emphasis>
|
||
occupies some additional area of the
|
||
<emphasis id="C5CF4546D13CFFE4FE30FB7AFE3BFA93" bold="true" box="[425,436,1264,1283]" italics="true" pageId="7" pageNumber="8">h</emphasis>
|
||
BuChE cavity given by the presence of the 3-ethylpiperidine moiety. This might become an area of interest for further structural changes to potentiate the inhibition ability of
|
||
<emphasis id="C5CF4546D13CFFE4FD78FAA2FD75FAAB" bold="true" box="[737,762,1320,1339]" pageId="7" pageNumber="8">19</emphasis>
|
||
.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FFFDFAEAFF7AFAE3" blockId="7.[100,245,1376,1395]" box="[100,245,1376,1395]" pageId="7" pageNumber="8">
|
||
<heading id="AC4C2E38D13CFFE4FFFDFAEAFF7AFAE3" bold="true" box="[100,245,1376,1395]" fontSize="36" level="1" pageId="7" pageNumber="8" reason="1">
|
||
<emphasis id="C5CF4546D13CFFE4FFFDFAEAFF7AFAE3" bold="true" box="[100,245,1376,1395]" pageId="7" pageNumber="8">3. Conclusion</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FF1DFA12FE8CF8A1" blockId="7.[100,770,1432,1841]" pageId="7" pageNumber="8">
|
||
In conclusion, the detailed phytochemical study of aerial parts of
|
||
<taxonomicName id="30BBE2D7D13CFFE4FFFDFA3EFF3CFA57" box="[100,179,1460,1479]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="7" pageNumber="8" phylum="Tracheophyta" rank="species" species="minor">
|
||
<emphasis id="C5CF4546D13CFFE4FFFDFA3EFF3CFA57" bold="true" box="[100,179,1460,1479]" italics="true" pageId="7" pageNumber="8">V. minor</emphasis>
|
||
</taxonomicName>
|
||
led to the isolation of twenty-two known indole monoterpene alkaloids and one undescribed structure, named vincaminorudeine (
|
||
<emphasis id="C5CF4546D13CFFE4FD7EFA5AFD7CFA73" bold="true" box="[743,755,1488,1507]" pageId="7" pageNumber="8">9</emphasis>
|
||
). Some previously reported literature NMR data had to be revised and updated. Bioassays focused on determining the cholinesterase activity related to AD revealed that some isolated indole alkaloids are promising
|
||
<emphasis id="C5CF4546D13CFFE4FFFDF9B5FFE0F9C2" bold="true" box="[100,111,1599,1618]" italics="true" pageId="7" pageNumber="8">h</emphasis>
|
||
BuChE inhibitors. The most active structure, ()-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1
|
||
<emphasis id="C5CF4546D13CFFE4FEBFF9D1FEBAF9FE" bold="true" box="[294,309,1627,1646]" italics="true" pageId="7" pageNumber="8">H</emphasis>
|
||
-indole (
|
||
<emphasis id="C5CF4546D13CFFE4FE13F9D1FE2CF9FE" bold="true" box="[394,419,1627,1646]" pageId="7" pageNumber="8">19</emphasis>
|
||
), showed remarkable
|
||
<emphasis id="C5CF4546D13CFFE4FD1DF9D1FD00F9FE" bold="true" box="[644,655,1627,1646]" italics="true" pageId="7" pageNumber="8">h</emphasis>
|
||
BuChE, and POP inhibition potency. The possibility of blood-brain barrier penetration, enzyme kinetic analysis, and binding into the active site of
|
||
<emphasis id="C5CF4546D13CFFE4FD21F919FD4CF936" bold="true" box="[696,707,1683,1702]" italics="true" pageId="7" pageNumber="8">h</emphasis>
|
||
BuChE for
|
||
<emphasis id="C5CF4546D13CFFE4FF1FF925FF10F952" bold="true" box="[134,159,1711,1730]" pageId="7" pageNumber="8">19</emphasis>
|
||
was explored as well. The previously described synthetic routes leading to the preparation of this compound and compelling results from bioassays open an exploration possibility for its use in therapy or to classify the compound as a leading structure for the development of novel analogues.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FCABFF1EFC56FF36" blockId="7.[818,985,147,167]" box="[818,985,147,167]" pageId="7" pageNumber="8">
|
||
<emphasis id="C5CF4546D13CFFE4FCABFF1EFC56FF36" bold="true" box="[818,985,147,167]" pageId="7" pageNumber="8">4. Experimental</emphasis>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FCABFF41FB09FF4E" blockId="7.[818,1158,203,222]" box="[818,1158,203,222]" pageId="7" pageNumber="8">
|
||
<emphasis id="C5CF4546D13CFFE4FCABFF41FB09FF4E" bold="true" box="[818,1158,203,222]" italics="true" pageId="7" pageNumber="8">4.1. General experimental procedures</emphasis>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FCC8FE8EFB01FC24" blockId="7.[818,1488,259,948]" pageId="7" pageNumber="8">
|
||
NMR spectra were recorded for CDCl
|
||
<subScript id="6B3F9B11D13CFFE4FB2CFE81FB31FE89" attach="left" box="[1205,1214,267,281]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
solutions at laboratory temperature on a VNMR S500 (Varian) instrument operating at 500 MHz for proton nuclei and 125.7 MHz for carbon nuclei. Chemical shifts were recorded as δ values in parts per million (ppm) and were indirectly referenced to tetramethylsilane via the solvent signal (7.26 ppm for
|
||
<superScript id="00CE341CD13CFFE4FA2FFEE7FA30FEEB" attach="right" box="[1462,1471,365,379]" fontSize="6" pageId="7" pageNumber="8">1</superScript>
|
||
H and 77.0 ppm for
|
||
<superScript id="00CE341CD13CFFE4FC40FE03FC64FE07" attach="right" box="[985,1003,393,407]" fontSize="6" pageId="7" pageNumber="8">13</superScript>
|
||
C). The coupling constant (
|
||
<emphasis id="C5CF4546D13CFFE4FB71FE05FB7DFE32" bold="true" box="[1256,1266,399,418]" italics="true" pageId="7" pageNumber="8">J</emphasis>
|
||
) is given in Hz, and the chemical shifts are reported in ppm. For unambiguous assignment of
|
||
<superScript id="00CE341CD13CFFE4FA2FFE2FFA30FE23" attach="right" box="[1462,1471,421,435]" fontSize="6" pageId="7" pageNumber="8">1</superScript>
|
||
H and
|
||
<superScript id="00CE341CD13CFFE4FCC2FE4BFCE2FE5F" attach="right" box="[859,877,449,463]" fontSize="6" pageId="7" pageNumber="8">13</superScript>
|
||
C signals, 2D NMR spectra (gCOSY, gHSQC, gHMBCAD, gH2BC, and NOESY) were obtained using standard parameter sets and pulse programs delivered by the manufacturer of the spectrometer. The MS (ESI) were measured on a Thermo Finnigan LCQDuo spectrometer. The HRMS (ESI) were obtained on a hybrid quadrupole-time-of-flight (Q- TOF) spectrometer (Waters Synapt G2Si coupled to a Waters Acquity I- Class
|
||
<taxonomicName id="30BBE2D7D13CFFE4FCF4FDE4FB8BFD11" authority="System" authorityName="System" box="[877,1028,622,641]" class="Uhplc" pageId="7" pageNumber="8" rank="class">UHPLC System</taxonomicName>
|
||
). Optical rotation was measured on a P3000 polarimeter in either CHCl
|
||
<subScript id="6B3F9B11D13CFFE4FBBEFD1BFBBFFD0F" attach="left" box="[1063,1072,657,671]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
or MeOH. Thin-layer chromatography (TLC) was carried out on Merck precoated silica gel F254 plates; the development solvents used were mixtures of cyclohexane (cHx),
|
||
<emphasis id="C5CF4546D13CFFE4FAC2FD48FAE9FD45" bold="true" box="[1371,1382,706,725]" italics="true" pageId="7" pageNumber="8">n</emphasis>
|
||
-hexane (
|
||
<emphasis id="C5CF4546D13CFFE4FA24FD48FA47FD45" bold="true" box="[1469,1480,706,725]" italics="true" pageId="7" pageNumber="8">n</emphasis>
|
||
- Hx), toluene (To), chloroform (CHCl
|
||
<subScript id="6B3F9B11D13CFFE4FB10FD6FFB1DFD63" attach="left" box="[1161,1170,741,755]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
), acetone (Me
|
||
<subScript id="6B3F9B11D13CFFE4FA80FD6FFAADFD63" attach="both" box="[1305,1314,741,755]" fontSize="6" pageId="7" pageNumber="8">2</subScript>
|
||
CO), diethylamine (Et
|
||
<subScript id="6B3F9B11D13CFFE4FCD4FC8BFCD9FC9F" attach="both" box="[845,854,769,783]" fontSize="6" pageId="7" pageNumber="8">2</subScript>
|
||
NH), acetonitrile (ACN), ethyl acetate (EtOAc), ethanol (EtOH), light petroleum (LPE), and trifluoroacetic acid (TFAA). All used chemicals and solvents were obtained either from Sigma Aldrich (the
|
||
<collectingCountry id="8FACD9C4D13CFFE4FA0EFCBBFC06FCF0" name="Czech Republic" pageId="7" pageNumber="8">Czech Republic</collectingCountry>
|
||
), Penta – Ing. ˇSvec (the Cech Republic), Lach-Ner (the
|
||
<collectingCountry id="8FACD9C4D13CFFE4FA0EFCC7FC06FCEC" name="Czech Republic" pageId="7" pageNumber="8">Czech Republic</collectingCountry>
|
||
), or VWR International (
|
||
<collectingCountry id="8FACD9C4D13CFFE4FBEEFCE3FB33FCEC" box="[1143,1212,873,892]" name="France" pageId="7" pageNumber="8">France</collectingCountry>
|
||
). Compounds were observed under UV light (254 and
|
||
<quantity id="304334B1D13CFFE4FBACFC0FFB0BFC08" box="[1077,1156,901,920]" metricMagnitude="-7" metricUnit="m" metricValue="3.66" pageId="7" pageNumber="8" unit="nm" value="366.0">366 nm</quantity>
|
||
), and alkaloids were detected by spraying with Dragendorff’ s reagent.
|
||
</paragraph>
|
||
</subSubSection>
|
||
<subSubSection id="BFA1CADFD13CFFEAFCABFC53FC8DF83B" lastPageId="9" lastPageNumber="10" pageId="7" pageNumber="8" type="biology_ecology">
|
||
<paragraph id="F7049954D13CFFE4FCABFC53FC6EFC7C" blockId="7.[818,993,985,1004]" box="[818,993,985,1004]" pageId="7" pageNumber="8">
|
||
<emphasis id="C5CF4546D13CFFE4FCABFC53FC6EFC7C" bold="true" box="[818,993,985,1004]" italics="true" pageId="7" pageNumber="8">4.2. Plant material</emphasis>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FCC8FB9BFA35FB04" blockId="7.[818,1487,1041,1172]" pageId="7" pageNumber="8">
|
||
The dried aerial parts of
|
||
<taxonomicName id="30BBE2D7D13CFFE4FBA1FB9BFB2BFBB4" box="[1080,1188,1041,1060]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="7" pageNumber="8" phylum="Tracheophyta" rank="species" species="minor">
|
||
<emphasis id="C5CF4546D13CFFE4FBA1FB9BFB2BFBB4" bold="true" box="[1080,1188,1041,1060]" italics="true" pageId="7" pageNumber="8">Vinca minor</emphasis>
|
||
</taxonomicName>
|
||
L. (
|
||
<quantity id="304334B1D13CFFE4FB5EFB9BFB72FBB4" box="[1223,1277,1041,1060]" metricMagnitude="1" metricUnit="kg" metricValue="6.0" pageId="7" pageNumber="8" unit="kg" value="60.0">60 kg</quantity>
|
||
) were purchased from the herbal dealer Megafyt s.r.o. (Vrane´nad Vltavou, the
|
||
<collectingCountry id="8FACD9C4D13CFFE4FAD7FBA7FCC3FBCC" name="Czech Republic" pageId="7" pageNumber="8">Czech Republic</collectingCountry>
|
||
). The botanical verification was performed by prof. L. Opletal. The voucher specimen is deposited in the Department of Pharmaceutical Botany, Faculty of Pharmacy at Hradec Kr´alov´e, under code AL-350.
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FCABFB33FB26FB5C" blockId="7.[818,1193,1209,1228]" box="[818,1193,1209,1228]" pageId="7" pageNumber="8">
|
||
<emphasis id="C5CF4546D13CFFE4FCABFB33FB26FB5C" bold="true" box="[818,1193,1209,1228]" italics="true" pageId="7" pageNumber="8">4.3. Extraction and isolation of alkaloids</emphasis>
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FCC8FB7BFCC4F9A7" blockId="7.[818,1489,1265,1982]" pageId="7" pageNumber="8">
|
||
Finely cut and dried aerial parts of
|
||
<taxonomicName id="30BBE2D7D13CFFE4FB5DFB7BFA98FA94" box="[1220,1303,1265,1284]" class="Magnoliopsida" family="Apocynaceae" genus="Vinca" kingdom="Plantae" order="Gentianales" pageId="7" pageNumber="8" phylum="Tracheophyta" rank="species" species="minor">
|
||
<emphasis id="C5CF4546D13CFFE4FB5DFB7BFA98FA94" bold="true" box="[1220,1303,1265,1284]" italics="true" pageId="7" pageNumber="8">V. minor</emphasis>
|
||
</taxonomicName>
|
||
were minced and sequentially extracted with 95% EtOH (
|
||
<quantity id="304334B1D13CFFE4FB3DFA87FB55FAB1" box="[1188,1242,1293,1313]" metricMagnitude="-1" metricUnit="kg" metricValue="5.0" pageId="7" pageNumber="8" unit="g" value="500.0">500 g</quantity>
|
||
of material boiling with 3 L of EtOH for 30 min). The combined extracts were evaporated, and the dry residue was dissolved in 5% HCl. Hot distilled water was added, and the formed sediment (chlorophyll) was separated. After filtration, the extract was alkalized by an aqueous solution of NH
|
||
<subScript id="6B3F9B11D13CFFE4FAB8FA0EFAA5FA02" attach="left" box="[1313,1322,1412,1426]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
to pH 9–10. The precipitate was extracted with CHCl
|
||
<subScript id="6B3F9B11D13CFFE4FB11FA2AFB1EFA3E" attach="left" box="[1160,1169,1440,1454]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
(5 × 15 L). The combined CHCl
|
||
<subScript id="6B3F9B11D13CFFE4FA5FFA2AFA40FA3E" attach="left" box="[1478,1487,1440,1454]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
extracts were evaporated to dryness, yielding
|
||
<quantity id="304334B1D13CFFE4FB65FA3EFAB9FA58" box="[1276,1334,1460,1480]" metricMagnitude="-1" metricUnit="kg" metricValue="4.54" pageId="7" pageNumber="8" unit="g" value="454.0">454 g</quantity>
|
||
of dark brown alkaloidal residue. This residue was filtered through deactivated (by 6% of water) neutral aluminum oxide (
|
||
<quantity id="304334B1D13CFFE4FB1BFA66FB4DFA6F" box="[1154,1218,1516,1535]" metricMagnitude="0" metricUnit="kg" metricValue="4.5" pageId="7" pageNumber="8" unit="kg" value="4.5">4.5 kg</quantity>
|
||
), washing with CHCl
|
||
<subScript id="6B3F9B11D13CFFE4FA12FA7EFA1BF992" attach="left" box="[1419,1428,1524,1538]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
(9 L). The filtered extract was concentrated to give a dark brown residue (
|
||
<quantity id="304334B1D13CFFE4FA33F982FCCFF9A7" metricMagnitude="-1" metricUnit="kg" metricValue="2.0" pageId="7" pageNumber="8" unit="g" value="200.0">200 g</quantity>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D13CFFE4FCC8F9CAFB15F82E" blockId="7.[818,1489,1265,1982]" pageId="7" pageNumber="8">
|
||
This purified alkaloidal extract (
|
||
<quantity id="304334B1D13CFFE4FB14F9CAFB47F9C3" box="[1165,1224,1600,1619]" metricMagnitude="-1" metricUnit="kg" metricValue="2.0" pageId="7" pageNumber="8" unit="g" value="200.0">200 g</quantity>
|
||
) was separated by column chromatography on deactivated (by 6% of water) neutral aluminum oxide (
|
||
<quantity id="304334B1D13CFFE4FCEEF9F2FC29F91B" box="[887,934,1656,1675]" metricMagnitude="0" metricUnit="kg" metricValue="6.0" pageId="7" pageNumber="8" unit="kg" value="6.0">6 kg</quantity>
|
||
) eluted with LPE gradually enriched with CHCl
|
||
<subScript id="6B3F9B11D13CFFE4FA1DF9F5FA02F91D" attach="left" box="[1412,1421,1663,1677]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
(95:5, 90:10, 87.5:12.5, 85:15, 80:20, 75:25, 70:30, 65:35, 60:40, 55:45, 50:50, 45:55, 40:60, 30:70, 15:85), then with CHCl
|
||
<subScript id="6B3F9B11D13CFFE4FA89F93DFA96F955" attach="left" box="[1296,1305,1719,1733]" fontSize="6" pageId="7" pageNumber="8">3</subScript>
|
||
gradually enriched with EtOH (98:2, 98:4, 94:6, 92:8, 88:12, 80:20, 70:30, 60:40). In the end, the column was washed with pure EtOH. Each fraction was collected in 500 mL portions and was monitored by analytical TLC. Overall, over 500 fractions were collected; those with similar compositions were pooled together and evaporated to dryness, yielding 19 main fractions with an overall weight of
|
||
<quantity id="304334B1D13CFFE4FB17F8DDFB46F8FA" box="[1166,1225,1879,1898]" metricMagnitude="-1" metricUnit="kg" metricValue="1.42" pageId="7" pageNumber="8" unit="g" value="142.0">142 g</quantity>
|
||
. Based on TLC and GC-MS analysis, fraction No. 8 (
|
||
<quantity id="304334B1D13CFFE4FB80F8F9FBCAF816" box="[1049,1093,1907,1926]" metricMagnitude="-2" metricUnit="kg" metricValue="2.7" pageId="7" pageNumber="8" unit="g" value="27.0">27 g</quantity>
|
||
) appeared to be qualitatively and quantitatively the richest for alkaloids. Therefore, this fraction was chosen to be further processed and investigated.
|
||
</paragraph>
|
||
<caption id="A3C4C9DCD133FFEBFFFDFB10FC2BFABB" ID-DOI="http://doi.org/10.5281/zenodo.8240076" ID-Zenodo-Dep="8240076" httpUri="https://zenodo.org/record/8240076/files/figure.png" pageId="8" pageNumber="9" startId="8.[100,130,1178,1195]" targetBox="[208,1380,149,1150]" targetPageId="8" targetType="figure">
|
||
<paragraph id="F7049954D133FFEBFFFDFB10FC2BFABB" blockId="8.[100,1487,1178,1323]" pageId="8" pageNumber="9">
|
||
<emphasis id="C5CF4546D133FFEBFFFDFB10FF12FB3A" bold="true" box="[100,157,1178,1195]" pageId="8" pageNumber="9">Fig. 5.</emphasis>
|
||
The top-scored docking poses of
|
||
<emphasis id="C5CF4546D133FFEBFE20FB10FE40FB3B" bold="true" box="[441,463,1178,1195]" pageId="8" pageNumber="9">19</emphasis>
|
||
in
|
||
<emphasis id="C5CF4546D133FFEBFE73FB10FE7BFB3B" bold="true" box="[490,500,1178,1195]" italics="true" pageId="8" pageNumber="9">h</emphasis>
|
||
BuChE (A, B; PDB ID: 4BDS) and the crystal structure of tacrine bound to
|
||
<emphasis id="C5CF4546D133FFEBFBC6FB10FBE6FB3B" bold="true" box="[1119,1129,1178,1195]" italics="true" pageId="8" pageNumber="9">h</emphasis>
|
||
BuChE (C, D). The ligands are displayed in blue (A) and green (C) for
|
||
<emphasis id="C5CF4546D133FFEBFED8FB3EFED8FB55" bold="true" box="[321,343,1204,1221]" pageId="8" pageNumber="9">19</emphasis>
|
||
and tacrine, respectively; important amino acid residues responsible for ligand anchoring are shown in grey for
|
||
<emphasis id="C5CF4546D133FFEBFA9BFB39FA83FB54" bold="true" box="[1282,1292,1203,1220]" italics="true" pageId="8" pageNumber="9">h</emphasis>
|
||
BuChE (A, C). Catalytic triad residues are displayed in yellow (A, C). Important interactions are rendered by black dashed lines; distances are measured in angstroms (Å). The rest of the receptor is displayed in light-grey cartoon conformation (A, C). Figures A and C were created with The PyMOL Molecular Graphics System, Version 2.4.1, Schr¨odinger, LLC. 2D figures (B, D) were generated with Maestro 12.3 (Schr¨odinger Release, Schr¨odinger, LLC, New York, NY, 2020). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
|
||
</paragraph>
|
||
</caption>
|
||
<paragraph id="F7049954D133FFEBFF1DFADEFD71F9D6" blockId="8.[100,771,1364,1969]" pageId="8" pageNumber="9">
|
||
In the pursuit of isolation of pure alkaloidal compounds, fraction No. 8 was fractionated by column chromatography on deactivated (by 10% of water) silica gel (
|
||
<quantity id="304334B1D133FFEBFEB9FA01FED0FA0E" box="[288,351,1419,1438]" metricMagnitude="0" metricUnit="kg" metricValue="1.5" pageId="8" pageNumber="9" unit="kg" value="1.5">1.5 kg</quantity>
|
||
), eluting firstly with a mixture of CHCl
|
||
<subScript id="6B3F9B11D133FFEBFD49FA19FD56FA31" attach="left" box="[720,729,1427,1441]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
and LPE (80:20), then with pure CHCl
|
||
<subScript id="6B3F9B11D133FFEBFE39FA25FE26FA2D" attach="left" box="[416,425,1455,1469]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
, and after that with CHCl
|
||
<subScript id="6B3F9B11D133FFEBFD03FA25FD2CFA2D" attach="left" box="[666,675,1455,1469]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
gradually enriched with EtOH (99:1, 98:2, 95:5, 90:10). The fractions were collected in 500 mL portions and monitored by analytical TLC sprayed with Dragendorff’ s reagent. Overall, over 100 fractions were collected; those with similar alkaloidal TLC profiles were pooled together and evaporated to dryness, providing 8 main alkaloid-rich fractions (
|
||
<emphasis id="C5CF4546D133FFEBFD5EF9B9FD7FF9D6" bold="true" box="[711,752,1587,1607]" pageId="8" pageNumber="9">A–H</emphasis>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D133FFEBFF1DF9C5FF6EF925" blockId="8.[100,771,1364,1969]" pageId="8" pageNumber="9">
|
||
Fraction
|
||
<emphasis id="C5CF4546D133FFEBFF70F9C5FF77F9F2" bold="true" box="[233,248,1615,1634]" pageId="8" pageNumber="9">A</emphasis>
|
||
(
|
||
<quantity id="304334B1D133FFEBFE8CF9C5FEECF9F2" box="[277,355,1615,1634]" metricMagnitude="-4" metricUnit="kg" metricValue="5.8999999999999995" pageId="8" pageNumber="9" unit="g" value="0.59">0.59 g</quantity>
|
||
) was separated by preparative TLC (To–EtOAc–Et
|
||
<subScript id="6B3F9B11D133FFEBFF70F9F8FF7DF910" attach="both" box="[233,242,1650,1664]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
NH, 40:15:1, × 2) to yield vincaminorine (
|
||
<emphasis id="C5CF4546D133FFEBFD15F9E0FD17F9ED" bold="true" box="[652,664,1642,1661]" pageId="8" pageNumber="9">1</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFD3FF9E0FD77F9EE" box="[678,760,1642,1662]" metricMagnitude="-5" metricUnit="kg" metricValue="5.4399999999999995" pageId="8" pageNumber="9" unit="mg" value="54.4">54.4 mg</quantity>
|
||
), recrystallized from a solution of CHCl
|
||
<subScript id="6B3F9B11D133FFEBFE54F904FE59F90C" attach="left" box="[461,470,1678,1692]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
–EtOH 1:1, and vincaminoreine (
|
||
<emphasis id="C5CF4546D133FFEBFFF5F928FFF7F925" bold="true" box="[108,120,1698,1717]" pageId="8" pageNumber="9">2</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFF1CF928FF59F925" box="[133,214,1698,1717]" metricMagnitude="-5" metricUnit="kg" metricValue="2.58" pageId="8" pageNumber="9" unit="mg" value="25.8">25.8 mg</quantity>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D133FFEBFF1DF934FECAF805" blockId="8.[100,771,1364,1969]" pageId="8" pageNumber="9">
|
||
Fraction
|
||
<emphasis id="C5CF4546D133FFEBFF43F934FF67F941" bold="true" box="[218,232,1726,1745]" pageId="8" pageNumber="9">B</emphasis>
|
||
(
|
||
<quantity id="304334B1D133FFEBFF6EF934FECDF941" box="[247,322,1726,1745]" metricMagnitude="-2" metricUnit="kg" metricValue="1.182" pageId="8" pageNumber="9" unit="g" value="11.82">11.82 g</quantity>
|
||
) was dissolved in 5% HCl (pH 1) and filtered through Celite. The acidic solution of chlorides was extracted with Et
|
||
<subScript id="6B3F9B11D133FFEBFD70F96BFD7DF97F" attach="both" box="[745,754,1761,1775]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
O (4 × 50 mL) and evaporated. The residue was alkalized with 10% Na
|
||
<subScript id="6B3F9B11D133FFEBFFE7F893FF08F8B7" attach="both" box="[126,135,1817,1831]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
CO
|
||
<subScript id="6B3F9B11D133FFEBFF3DF893FF22F8B7" attach="left" box="[164,173,1817,1831]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
(pH 9–10), and the white precipitate was extracted with Et
|
||
<subScript id="6B3F9B11D133FFEBFD48F893FD55F8B7" attach="both" box="[721,730,1817,1831]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
O (5 × 50 mL) and evaporated once again. The alkaloidal residue was filtered and washed with distilled water, yielding
|
||
<quantity id="304334B1D133FFEBFD94F8C0FDC2F8CD" box="[525,589,1866,1885]" metricMagnitude="-3" metricUnit="kg" metricValue="5.21" pageId="8" pageNumber="9" unit="g" value="5.21">5.21 g</quantity>
|
||
of ocher powder. Recrystallization from a mixture of EtOH and water 1:1 yielded eburnamonine (
|
||
<emphasis id="C5CF4546D133FFEBFF49F80BFF53F804" bold="true" box="[208,220,1921,1940]" pageId="8" pageNumber="9">3</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFF70F80BFEB5F805" box="[233,314,1921,1941]" metricMagnitude="-5" metricUnit="kg" metricValue="3.75" pageId="8" pageNumber="9" unit="mg" value="37.5">37.5 mg</quantity>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D133FFEBFF1DF817FBACF8B5" blockId="8.[100,771,1364,1969]" lastBlockId="8.[818,1488,1364,1969]" pageId="8" pageNumber="9">
|
||
Fraction
|
||
<emphasis id="C5CF4546D133FFEBFF7FF817FF7BF820" bold="true" box="[230,244,1949,1968]" pageId="8" pageNumber="9">C</emphasis>
|
||
(
|
||
<quantity id="304334B1D133FFEBFE96F817FED5F821" box="[271,346,1949,1969]" metricMagnitude="-3" metricUnit="kg" metricValue="1.36" pageId="8" pageNumber="9" unit="g" value="1.36">1.36 g</quantity>
|
||
) was treated by preparative TLC (
|
||
<emphasis id="C5CF4546D133FFEBFD69F814FD74F821" bold="true" box="[752,763,1950,1969]" italics="true" pageId="8" pageNumber="9">n</emphasis>
|
||
- Hx–EtOAc–Et
|
||
<subScript id="6B3F9B11D133FFEBFC29FAD1FC36FAF9" attach="both" box="[944,953,1371,1385]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
NH, 30:11:1, × 2) to give six alkaloidal subfractions (
|
||
<emphasis id="C5CF4546D133FFEBFCA3FAE5FCF7FA12" bold="true" box="[826,888,1391,1412]" pageId="8" pageNumber="9">C1–C6</emphasis>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D133FFEBFC65FAE5FB99FA12" bold="true" box="[1020,1046,1391,1410]" pageId="8" pageNumber="9">C1</emphasis>
|
||
was purified multiple times by preparative TLC in various mobile phases (mixtures of CHCl
|
||
<subScript id="6B3F9B11D133FFEBFB5AFA19FB43FA31" attach="left" box="[1219,1228,1427,1441]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
, EtOAc, ACN, and TFAA) to finally yield minovine (
|
||
<emphasis id="C5CF4546D133FFEBFB81FA2DFBABFA2A" bold="true" box="[1048,1060,1447,1466]" pageId="8" pageNumber="9">4</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFBADFA2DFB07FA2B" box="[1076,1160,1447,1467]" metricMagnitude="-5" metricUnit="kg" metricValue="1.26" pageId="8" pageNumber="9" unit="mg" value="12.6">12.6 mg</quantity>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D133FFEBFA89FA2DFAA5FA2A" bold="true" box="[1296,1322,1447,1466]" pageId="8" pageNumber="9">C2</emphasis>
|
||
was joined with subfraction
|
||
<emphasis id="C5CF4546D133FFEBFC38FA49FC31FA46" bold="true" box="[929,958,1475,1494]" pageId="8" pageNumber="9">G1</emphasis>
|
||
and purified by preparative TLC to give 16-methoxyminovine (
|
||
<emphasis id="C5CF4546D133FFEBFCE6FA55FC04FA62" bold="true" box="[895,907,1503,1522]" pageId="8" pageNumber="9">5</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFC0FFA55FC69FA62" box="[918,998,1503,1522]" metricMagnitude="-5" metricUnit="kg" metricValue="2.73" pageId="8" pageNumber="9" unit="mg" value="27.3">27.3 mg</quantity>
|
||
). TLC separation of subfraction
|
||
<emphasis id="C5CF4546D133FFEBFA97FA55FAA7FA62" bold="true" box="[1294,1320,1503,1522]" pageId="8" pageNumber="9">
|
||
C
|
||
<quantity id="304334B1D133FFEBFA84FA55FAA7FA62" box="[1309,1320,1503,1522]" metricMagnitude="-2" metricUnit="m" metricValue="7.62" pageId="8" pageNumber="9" unit="in" value="3.0">3</quantity>
|
||
</emphasis>
|
||
in various mobile phases (mixtures of cHx, LPE, and Et
|
||
<subScript id="6B3F9B11D133FFEBFB09F988FB16F980" attach="both" box="[1168,1177,1538,1552]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
NH) led to the isolation of a diastereoisomeric mixture 3:2 of vincatine (
|
||
<emphasis id="C5CF4546D133FFEBFB22F99DFB48F9BA" bold="true" box="[1211,1223,1559,1578]" pageId="8" pageNumber="9">6</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFB4CF99DFAA7F9BA" box="[1237,1320,1559,1578]" metricMagnitude="-5" metricUnit="kg" metricValue="9.809999999999999" pageId="8" pageNumber="9" unit="mg" value="98.1">98.1 mg</quantity>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D133FFEBFA36F99DFA46F9BA" bold="true" box="[1455,1481,1559,1578]" pageId="8" pageNumber="9">C4</emphasis>
|
||
, after treatment by preparative TLC (cHx–Et
|
||
<subScript id="6B3F9B11D133FFEBFB57F9B0FB58F9D8" attach="both" box="[1230,1239,1594,1608]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
NH, 95:5, × 2) and purification (CHCl
|
||
<subScript id="6B3F9B11D133FFEBFC34F9DCFC39F9F4" attach="left" box="[941,950,1622,1636]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
–ACN–TFAA, 40:10:0.1, × 1), afforded minovincine (
|
||
<emphasis id="C5CF4546D133FFEBFA24F9C5FA46F9F2" bold="true" box="[1469,1481,1615,1634]" pageId="8" pageNumber="9">7</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFCABF9E1FC1FF9EE" box="[818,912,1643,1662]" metricMagnitude="-5" metricUnit="kg" metricValue="4.4399999999999995" pageId="8" pageNumber="9" unit="mg" value="44.4">44.4 mg</quantity>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D133FFEBFBB4F9E0FBC7F9ED" bold="true" box="[1069,1096,1642,1661]" pageId="8" pageNumber="9">C5</emphasis>
|
||
was separated by preparative TLC (CHCl
|
||
<subScript id="6B3F9B11D133FFEBFCF3F904FCFCF90C" attach="left" box="[874,883,1678,1692]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
–ACN–TFAA, 40:10:0.1, × 1) to yield 16-methoxyminovincine (
|
||
<quantity id="304334B1D133FFEBFCA3F928FC3AF925" box="[826,949,1698,1718]" metricMagnitude="-3" metricUnit="kg" metricValue="8.1282" pageId="8" pageNumber="9" unit="mg" value="8128.2">
|
||
<emphasis id="C5CF4546D133FFEBFCA3F928FCC9F925" bold="true" box="[826,838,1698,1717]" pageId="8" pageNumber="9">8</emphasis>
|
||
, 128.2 mg
|
||
</quantity>
|
||
) and another compound, which after TLC purification (cHx–To–Et
|
||
<subScript id="6B3F9B11D133FFEBFC06F94FFC27F943" attach="both" box="[927,936,1733,1747]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
NH, 65:30:5, × 2), afforded the undescribed alkaloid vincaminorudeine (
|
||
<emphasis id="C5CF4546D133FFEBFC55F950FC57F97D" bold="true" box="[972,984,1754,1773]" pageId="8" pageNumber="9">9</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFC7DF950FBBBF97D" box="[996,1076,1754,1773]" metricMagnitude="-5" metricUnit="kg" metricValue="1.88" pageId="8" pageNumber="9" unit="mg" value="18.8">18.8 mg</quantity>
|
||
). Finally, subfraction
|
||
<emphasis id="C5CF4546D133FFEBFA99F950FA95F97D" bold="true" box="[1280,1306,1754,1773]" pageId="8" pageNumber="9">C6</emphasis>
|
||
, after treatment by preparative TLC (cHx–Et
|
||
<subScript id="6B3F9B11D133FFEBFBB6F977FBB7F89B" attach="both" box="[1071,1080,1789,1803]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
NH, 95:5, × 2), yielded demethoxyalstonamide (
|
||
<emphasis id="C5CF4546D133FFEBFC38F898FC35F8B5" bold="true" box="[929,954,1810,1829]" pageId="8" pageNumber="9">10</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFC5FF898FB98F8B5" box="[966,1047,1810,1829]" metricMagnitude="-5" metricUnit="kg" metricValue="1.97" pageId="8" pageNumber="9" unit="mg" value="19.7">19.7 mg</quantity>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D133FFEAFCC8F8A4FB30FF53" blockId="8.[818,1488,1364,1969]" lastBlockId="9.[818,1487,148,195]" lastPageId="9" lastPageNumber="10" pageId="8" pageNumber="9">
|
||
Preparative TLC (cHx–Et
|
||
<subScript id="6B3F9B11D133FFEBFBA5F8BFFBCAF8D3" attach="both" box="[1084,1093,1845,1859]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
NH, 95:5, × 2) was used to separate fraction
|
||
<emphasis id="C5CF4546D133FFEBFCC7F8C0FCE2F8CD" bold="true" box="[862,877,1866,1885]" pageId="8" pageNumber="9">D</emphasis>
|
||
(
|
||
<quantity id="304334B1D133FFEBFCE5F8C0FC34F8CD" box="[892,955,1866,1885]" metricMagnitude="-3" metricUnit="kg" metricValue="3.13" pageId="8" pageNumber="9" unit="g" value="3.13">3.13 g</quantity>
|
||
) into four alkaloidal subfractions (
|
||
<emphasis id="C5CF4546D133FFEBFA92F8C0FAC2F8CD" bold="true" box="[1291,1357,1866,1886]" pageId="8" pageNumber="9">D1–D4</emphasis>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D133FFEBFCABF8ECFCC2F8E9" bold="true" box="[818,845,1894,1913]" pageId="8" pageNumber="9">D1</emphasis>
|
||
, after purification by preparative TLC in various mobile phases (mixtures of CHCl
|
||
<subScript id="6B3F9B11D133FFEBFC40F803FC6DF807" attach="left" box="[985,994,1929,1943]" fontSize="6" pageId="8" pageNumber="9">3</subScript>
|
||
, ACN, TFAA, cHx, To, and Et
|
||
<subScript id="6B3F9B11D133FFEBFB6BF803FB74F807" attach="both" box="[1266,1275,1929,1943]" fontSize="6" pageId="8" pageNumber="9">2</subScript>
|
||
NH), yielded vincorine (
|
||
<emphasis id="C5CF4546D133FFEBFCA3F817FCDCF820" bold="true" box="[826,851,1949,1968]" pageId="8" pageNumber="9">11</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFCFBF814FC3AF821" box="[866,949,1950,1969]" metricMagnitude="-5" metricUnit="kg" metricValue="3.3899999999999997" pageId="8" pageNumber="9" unit="mg" value="33.9">33.9 mg</quantity>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D133FFEBFBA7F817FBD5F820" bold="true" box="[1086,1114,1949,1968]" pageId="8" pageNumber="9">D2</emphasis>
|
||
contained eburnamonine (
|
||
<emphasis id="C5CF4546D133FFEBFAFBF817FAE1F820" bold="true" box="[1378,1390,1949,1968]" pageId="8" pageNumber="9">3</emphasis>
|
||
,
|
||
<quantity id="304334B1D133FFEBFAE4F814FA4AF821" box="[1405,1477,1950,1969]" metricMagnitude="-6" metricUnit="kg" metricValue="9.8" pageId="8" pageNumber="9" unit="mg" value="9.8">9.8 mg</quantity>
|
||
). of subfraction
|
||
<emphasis id="C5CF4546D132FFEAFC21FF1EFC5BFF37" bold="true" box="[952,980,148,167]" pageId="9" pageNumber="10">H5</emphasis>
|
||
by TLC (EtOAc–MeOH–Et
|
||
<subScript id="6B3F9B11D132FFEAFB51FF11FB5EFF39" attach="both" box="[1224,1233,155,169]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 40:10:2, × 1) achieved the isolation of raucubaine (
|
||
<emphasis id="C5CF4546D132FFEAFBA4FF3AFBD9FF53" bold="true" box="[1085,1110,176,195]" pageId="9" pageNumber="10">23</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFBFBFF3AFB3BFF53" box="[1122,1204,176,195]" metricMagnitude="-5" metricUnit="kg" metricValue="1.24" pageId="9" pageNumber="10" unit="mg" value="12.4">12.4 mg</quantity>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCABFF6DFBB4FF6A" blockId="9.[818,1083,231,250]" box="[818,1083,231,250]" pageId="9" pageNumber="10">
|
||
<heading id="AC4C2E38D132FFEAFCABFF6DFBB4FF6A" bold="true" box="[818,1083,231,250]" fontSize="36" level="1" pageId="9" pageNumber="10" reason="1">
|
||
<emphasis id="C5CF4546D132FFEAFCABFF6DFBB4FF6A" bold="true" box="[818,1083,231,250]" italics="true" pageId="9" pageNumber="10">4.3.1. Vincaminorudeine (9)</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCC8FE82FC76FEFF" blockId="9.[818,1487,257,367]" pageId="9" pageNumber="10">
|
||
Lightly brown crystals; [
|
||
<emphasis id="C5CF4546D132FFEAFBA0FE8DFBCAFE8C" box="[1081,1093,263,284]" italics="true" pageId="9" pageNumber="10">α</emphasis>
|
||
]
|
||
<emphasis id="C5CF4546D132FFEAFBD2FE98FBDAFEB0" bold="true" box="[1099,1109,274,288]" italics="true" pageId="9" pageNumber="10">
|
||
<subScript id="6B3F9B11D132FFEAFBD2FE98FBDAFEB0" attach="left" box="[1099,1109,274,288]" fontSize="6" pageId="9" pageNumber="10">D</subScript>
|
||
</emphasis>
|
||
<superScript id="00CE341CD132FFEAFBD2FE8BFBD3FE9F" attach="left" box="[1099,1116,257,271]" fontSize="6" pageId="9" pageNumber="10">27</superScript>
|
||
+ 27.8 (c 0.1, CHCl
|
||
<subScript id="6B3F9B11D132FFEAFABDFE85FAA2FE8D" attach="left" box="[1316,1325,271,285]" fontSize="6" pageId="9" pageNumber="10">3</subScript>
|
||
); for
|
||
<superScript id="00CE341CD132FFEAFAFCFE88FAE1FE80" attach="right" box="[1381,1390,258,272]" fontSize="6" pageId="9" pageNumber="10">1</superScript>
|
||
H and
|
||
<superScript id="00CE341CD132FFEAFA29FE88FA4DFE80" attach="right" box="[1456,1474,258,272]" fontSize="6" pageId="9" pageNumber="10">13</superScript>
|
||
C NMR data see
|
||
<tableCitation id="BA39ACEFD132FFEAFC48FEAEFB90FEA7" box="[977,1055,292,311]" captionStart="Table 1" captionStartId="3.[100,150,150,166]" captionTargetPageId="3" captionText="Table 1 Key correlations from 2D NMR experiments in the structure elucidation of undescribed alkaloid 9 (HMBC interaction – blue arrow; H2BC and COSY interaction – red bond) and its 1H and 13C NMR chemical shifts assigned to the related position in ppm with coupling constants (in parenthesis, reported in Hz).." httpUri="http://table.plazi.org/id/A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D" pageId="9" pageNumber="10" tableUuid="A3C4C9DCD138FFE0FFFDFF1CFC8DFE9D">Table 1</tableCitation>
|
||
; HRMS
|
||
<emphasis id="C5CF4546D132FFEAFBE2FEAEFB2FFEA7" bold="true" box="[1147,1184,292,311]" italics="true" pageId="9" pageNumber="10">m/z</emphasis>
|
||
371.2339 [M+ H]
|
||
<superScript id="00CE341CD132FFEAFAC3FEAAFAEBFEBC" attach="left" box="[1370,1380,288,300]" fontSize="6" pageId="9" pageNumber="10">+</superScript>
|
||
(calc. for C
|
||
<subScript id="6B3F9B11D132FFEAFCA6FECDFCDEFEC5" attach="both" box="[831,849,327,341]" fontSize="6" pageId="9" pageNumber="10">22</subScript>
|
||
H
|
||
<subScript id="6B3F9B11D132FFEAFCF8FECDFCFCFEC5" attach="both" box="[865,883,327,341]" fontSize="6" pageId="9" pageNumber="10">30</subScript>
|
||
N
|
||
<subScript id="6B3F9B11D132FFEAFC1BFECDFC04FEC5" attach="both" box="[898,907,327,341]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
O
|
||
<subScript id="6B3F9B11D132FFEAFC02FECDFC2BFEC5" attach="left" box="[923,932,327,341]" fontSize="6" pageId="9" pageNumber="10">3</subScript>
|
||
<superScript id="00CE341CD132FFEAFC3AFEB6FC22FED8" attach="right" box="[931,941,316,328]" fontSize="6" pageId="9" pageNumber="10">+</superScript>
|
||
, 371.2329); for HRMS and 1D and 2D NMR spectra see the Supplementary Data.
|
||
</paragraph>
|
||
<caption id="A3C4C9DCD132FFEAFFFDFD0DFEA8FCDB" ID-DOI="http://doi.org/10.5281/zenodo.8240078" ID-Zenodo-Dep="8240078" httpUri="https://zenodo.org/record/8240078/files/figure.png" pageId="9" pageNumber="10" startId="9.[100,130,647,664]" targetBox="[108,765,150,618]" targetPageId="9" targetType="figure">
|
||
<paragraph id="F7049954D132FFEAFFFDFD0DFEA8FCDB" blockId="9.[100,770,647,843]" pageId="9" pageNumber="10">
|
||
<emphasis id="C5CF4546D132FFEAFFFDFD0DFF12FD08" bold="true" box="[100,157,647,664]" pageId="9" pageNumber="10">Fig. 6.</emphasis>
|
||
Overlapped top-scored poses for ligands
|
||
<emphasis id="C5CF4546D132FFEAFE66FD0DFD9AFD08" bold="true" box="[511,533,647,664]" pageId="9" pageNumber="10">19</emphasis>
|
||
(blue) and crystal structure of tacrine (green) in the active site of
|
||
<emphasis id="C5CF4546D132FFEAFE25FD2BFE49FD22" bold="true" box="[444,454,673,690]" italics="true" pageId="9" pageNumber="10">h</emphasis>
|
||
BuChE (PDB ID: 4BDS). Amino acid residues involved in the interactions with ligands are depicted as either grey or yellow (catalytic triad) lines. The rest of the receptor is displayed in light-grey cartoon conformation. The Figure was created with The PyMOL Molecular Graphics System, Version 2.4.1, Schr¨odinger, LLC. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
|
||
</paragraph>
|
||
</caption>
|
||
<paragraph id="F7049954D132FFEAFFFDFCFEFE08FB83" blockId="9.[100,771,884,1963]" pageId="9" pageNumber="10">
|
||
Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFF47FCFEFF75FC17" bold="true" box="[222,250,884,903]" pageId="9" pageNumber="10">D3</emphasis>
|
||
, after further preparative TLC (cHx–EtOAc–Et
|
||
<subScript id="6B3F9B11D132FFEAFD4DFCF1FD52FC19" attach="both" box="[724,733,891,905]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 70:30:1, × 1), gave vincaminorudeine (
|
||
<emphasis id="C5CF4546D132FFEAFE4BFC1AFE51FC33" bold="true" box="[466,478,912,931]" pageId="9" pageNumber="10">9</emphasis>
|
||
, 26.0 mg) and a mixture of two alkaloids, which after TLC separation (CHCl
|
||
<subScript id="6B3F9B11D132FFEAFD9BFC39FD84FC51" attach="left" box="[514,523,947,961]" fontSize="6" pageId="9" pageNumber="10">3</subScript>
|
||
–ACN–TFAA, 40:10:0.1, × 1) yielded 16-methoxyminovincine (
|
||
<emphasis id="C5CF4546D132FFEAFE57FC42FE55FC4B" bold="true" box="[462,474,968,987]" pageId="9" pageNumber="10">8</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFE75FC42FDCEFC4B" box="[492,577,968,987]" metricMagnitude="-5" metricUnit="kg" metricValue="2.44" pageId="9" pageNumber="10" unit="mg" value="24.4">24.4 mg</quantity>
|
||
) and demethoxyalstonamide (
|
||
<emphasis id="C5CF4546D132FFEAFF40FC69FF7DFC66" bold="true" box="[217,242,995,1014]" pageId="9" pageNumber="10">10</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFE9AFC6EFEC1FC67" box="[259,334,996,1015]" metricMagnitude="-6" metricUnit="kg" metricValue="8.2" pageId="9" pageNumber="10" unit="mg" value="8.2">8.2 mg</quantity>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFE42FC69FE78FC66" bold="true" box="[475,503,995,1014]" pageId="9" pageNumber="10">D4</emphasis>
|
||
was entirely composed of minovincinine (
|
||
<quantity id="304334B1D132FFEAFF63FC75FEF3FB83" box="[250,380,1023,1043]" metricMagnitude="-2" metricUnit="kg" metricValue="1.24994" pageId="9" pageNumber="10" unit="mg" value="12499.4">
|
||
<emphasis id="C5CF4546D132FFEAFF63FC75FE9CFB82" bold="true" box="[250,275,1023,1042]" pageId="9" pageNumber="10">12</emphasis>
|
||
, 499.4 mg
|
||
</quantity>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFF1DFB91FD69FAD5" blockId="9.[100,771,884,1963]" pageId="9" pageNumber="10">
|
||
Fraction
|
||
<emphasis id="C5CF4546D132FFEAFF7DFB91FF7EFBBE" bold="true" box="[228,241,1051,1070]" pageId="9" pageNumber="10">E</emphasis>
|
||
(
|
||
<quantity id="304334B1D132FFEAFE93FB91FEDCFBBE" box="[266,339,1051,1070]" metricMagnitude="-3" metricUnit="kg" metricValue="1.02" pageId="9" pageNumber="10" unit="g" value="1.02">1.02 g</quantity>
|
||
) was subjected to preparative TLC (
|
||
<emphasis id="C5CF4546D132FFEAFD69FB96FC8DFBBF" bold="true" box="[752,770,1052,1071]" italics="true" pageId="9" pageNumber="10">n-</emphasis>
|
||
Hx–EtOAc–Et
|
||
<subScript id="6B3F9B11D132FFEAFF7AFBB4FF63FBDC" attach="both" box="[227,236,1086,1100]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 30:11:1, × 2) to give three subfractions (
|
||
<emphasis id="C5CF4546D132FFEAFD2EFBBDFD7BFBDA" bold="true" box="[695,756,1079,1099]" pageId="9" pageNumber="10">E1–E3</emphasis>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFF4EFBD9FF7FFBF6" bold="true" box="[215,240,1107,1126]" pageId="9" pageNumber="10">E1</emphasis>
|
||
was purified by TLC (cHx–LPE–Et
|
||
<subScript id="6B3F9B11D132FFEAFDACFBD0FDB1FBF8" attach="both" box="[565,574,1114,1128]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 80:20:4, × 3) to obtain aspidospermidine (
|
||
<emphasis id="C5CF4546D132FFEAFEC6FBE5FEF7FB12" bold="true" box="[351,376,1135,1154]" pageId="9" pageNumber="10">13</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFE1FFBE5FE55FB12" box="[390,474,1135,1154]" metricMagnitude="-5" metricUnit="kg" metricValue="3.6799999999999997" pageId="9" pageNumber="10" unit="mg" value="36.8">36.8 mg</quantity>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFDF8FBE5FDF5FB12" bold="true" box="[609,634,1135,1154]" pageId="9" pageNumber="10">E2</emphasis>
|
||
, merged with subfraction
|
||
<emphasis id="C5CF4546D132FFEAFF4FFB01FF7DFB0E" bold="true" box="[214,242,1163,1182]" pageId="9" pageNumber="10">G3</emphasis>
|
||
, was purified by repetitive TLC (To–Et
|
||
<subScript id="6B3F9B11D132FFEAFDF3FB18FDFCFB30" attach="both" box="[618,627,1170,1184]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 95:5, × 1; and To–Et
|
||
<subScript id="6B3F9B11D132FFEAFF5AFB24FF43FB2C" attach="both" box="[195,204,1198,1212]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 95:5, × 1) to afford 19-oxoeburnamonine (
|
||
<emphasis id="C5CF4546D132FFEAFD1DFB2DFD12FB2A" bold="true" box="[644,669,1191,1210]" pageId="9" pageNumber="10">14</emphasis>
|
||
, 10.0 mg). Separation of subfraction
|
||
<emphasis id="C5CF4546D132FFEAFEC2FB49FEFAFB46" bold="true" box="[347,373,1219,1238]" pageId="9" pageNumber="10">E3</emphasis>
|
||
(joined together with subfraction
|
||
<emphasis id="C5CF4546D132FFEAFD26FB49FD54FB46" bold="true" box="[703,731,1219,1238]" pageId="9" pageNumber="10">H3</emphasis>
|
||
) by preparative TLC (CHCl
|
||
<subScript id="6B3F9B11D132FFEAFEDAFB6CFEC3FB64" attach="left" box="[323,332,1254,1268]" fontSize="6" pageId="9" pageNumber="10">3</subScript>
|
||
–ACN–TFAA, 40:10: 0.1, × 5) provided two alkaloidal zones, which after purification by further preparative TLC (
|
||
<emphasis id="C5CF4546D132FFEAFD69FB71FC8DFA9E" bold="true" box="[752,770,1275,1294]" italics="true" pageId="9" pageNumber="10">n-</emphasis>
|
||
Hx–To–Et
|
||
<subScript id="6B3F9B11D132FFEAFF59FA94FF46FABC" attach="both" box="[192,201,1310,1324]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 45:45:10, × 2; and To–CHCl
|
||
<subScript id="6B3F9B11D132FFEAFD80FA94FDADFABC" attach="left" box="[537,546,1310,1324]" fontSize="6" pageId="9" pageNumber="10">3</subScript>
|
||
–Et
|
||
<subScript id="6B3F9B11D132FFEAFDD9FA94FDC6FABC" attach="both" box="[576,585,1310,1324]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 70:25:5, × 2) afforded akuammicine (
|
||
<emphasis id="C5CF4546D132FFEAFEDFFAB8FED0FAD5" bold="true" box="[326,351,1330,1349]" pageId="9" pageNumber="10">15</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFEF5FAB8FE20FAD5" box="[364,431,1330,1349]" metricMagnitude="-6" metricUnit="kg" metricValue="8.9" pageId="9" pageNumber="10" unit="mg" value="8.9">8.9 mg</quantity>
|
||
) and tubotaiwine (
|
||
<emphasis id="C5CF4546D132FFEAFDFDFAB8FDF2FAD5" bold="true" box="[612,637,1330,1349]" pageId="9" pageNumber="10">16</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFD10FAB8FD55FAD5" box="[649,730,1330,1349]" metricMagnitude="-5" metricUnit="kg" metricValue="2.7399999999999998" pageId="9" pageNumber="10" unit="mg" value="27.4">27.4 mg</quantity>
|
||
).
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFF1DFAC4FE4FFA09" blockId="9.[100,771,884,1963]" pageId="9" pageNumber="10">
|
||
Fraction
|
||
<emphasis id="C5CF4546D132FFEAFF79FAC4FF63FAF1" bold="true" box="[224,236,1358,1377]" pageId="9" pageNumber="10">F</emphasis>
|
||
(
|
||
<quantity id="304334B1D132FFEAFE99FAC4FECAFAF1" box="[256,325,1358,1377]" metricMagnitude="-4" metricUnit="kg" metricValue="8.7" pageId="9" pageNumber="10" unit="g" value="0.87">0.87 g</quantity>
|
||
), treated by repetitive preparative TLC (
|
||
<emphasis id="C5CF4546D132FFEAFD69FAC4FD74FAF1" bold="true" box="[752,763,1358,1377]" italics="true" pageId="9" pageNumber="10">n</emphasis>
|
||
- Hx–EtOAc–Et
|
||
<subScript id="6B3F9B11D132FFEAFF7AFAFBFF63FAEF" attach="both" box="[227,236,1393,1407]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 30:11:1, × 2), yielded raucubainine (
|
||
<emphasis id="C5CF4546D132FFEAFDE6FAE0FD17FAED" bold="true" box="[639,664,1386,1405]" pageId="9" pageNumber="10">17</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFD3CFAE0FD77FAED" box="[677,760,1386,1405]" metricMagnitude="-5" metricUnit="kg" metricValue="2.65" pageId="9" pageNumber="10" unit="mg" value="26.5">26.5 mg</quantity>
|
||
), which was recrystallized from EtOH.
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFF1DFA28FDD4F9B5" blockId="9.[100,771,884,1963]" pageId="9" pageNumber="10">
|
||
Fraction
|
||
<emphasis id="C5CF4546D132FFEAFF40FA28FF67FA25" bold="true" box="[217,232,1442,1461]" pageId="9" pageNumber="10">G</emphasis>
|
||
(
|
||
<quantity id="304334B1D132FFEAFF6FFA28FEBCFA25" box="[246,307,1442,1461]" metricMagnitude="-4" metricUnit="kg" metricValue="4.1" pageId="9" pageNumber="10" unit="g" value="0.41">0.41 g</quantity>
|
||
) was separated by preparative TLC to give three alkaloidal subfractions (
|
||
<emphasis id="C5CF4546D132FFEAFED2FA34FE02FA41" bold="true" box="[331,397,1470,1490]" pageId="9" pageNumber="10">G1–G3</emphasis>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFD8EFA34FDBCFA41" bold="true" box="[535,563,1470,1489]" pageId="9" pageNumber="10">G1</emphasis>
|
||
was joined with subfraction
|
||
<emphasis id="C5CF4546D132FFEAFF2CFA50FF5FFA7D" bold="true" box="[181,208,1498,1517]" pageId="9" pageNumber="10">C2</emphasis>
|
||
. Purification of subfraction
|
||
<emphasis id="C5CF4546D132FFEAFE79FA50FE74FA7D" bold="true" box="[480,507,1498,1517]" pageId="9" pageNumber="10">G2</emphasis>
|
||
by TLC (To–EtOAc–Et
|
||
<subScript id="6B3F9B11D132FFEAFD4DFA6BFD52FA7F" attach="both" box="[724,733,1505,1519]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 40:15:1, × 1) led to the acquisition of minovincine (
|
||
<emphasis id="C5CF4546D132FFEAFDC2FA7CFDE8F999" bold="true" box="[603,615,1526,1545]" pageId="9" pageNumber="10">7</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFDECFA7CFD48F999" box="[629,711,1526,1545]" metricMagnitude="-5" metricUnit="kg" metricValue="4.029999999999999" pageId="9" pageNumber="10" unit="mg" value="40.3">40.3 mg</quantity>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFF2DF99BFF5FF9B4" bold="true" box="[180,208,1553,1572]" pageId="9" pageNumber="10">G3</emphasis>
|
||
was pooled together with subfraction
|
||
<emphasis id="C5CF4546D132FFEAFDA5F99BFDDAF9B4" bold="true" box="[572,597,1553,1572]" pageId="9" pageNumber="10">E1</emphasis>
|
||
.
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFF1DF9A7FC8DF83B" blockId="9.[100,771,884,1963]" pageId="9" pageNumber="10">
|
||
Fraction
|
||
<emphasis id="C5CF4546D132FFEAFF47F9A7FF61F9D0" bold="true" box="[222,238,1581,1600]" pageId="9" pageNumber="10">H</emphasis>
|
||
(
|
||
<quantity id="304334B1D132FFEAFE98F9A7FECAF9D0" box="[257,325,1581,1600]" metricMagnitude="-3" metricUnit="kg" metricValue="2.38" pageId="9" pageNumber="10" unit="g" value="2.38">2.38 g</quantity>
|
||
), after treatment by preparative TLC (
|
||
<emphasis id="C5CF4546D132FFEAFD56F9A4FD55F9D1" bold="true" box="[719,730,1582,1601]" italics="true" pageId="9" pageNumber="10">n</emphasis>
|
||
-Hx: To–EtOAc–Et
|
||
<subScript id="6B3F9B11D132FFEAFF78F9DAFF65F9CE" attach="both" box="[225,234,1616,1630]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 20:10:11:1, × 3), afforded five main subfractions (
|
||
<emphasis id="C5CF4546D132FFEAFFF5F9EFFF3EF9E8" bold="true" box="[108,177,1637,1657]" pageId="9" pageNumber="10">H1–H5</emphasis>
|
||
). Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFEAFF9EFFEDCF9E8" bold="true" box="[310,339,1637,1656]" pageId="9" pageNumber="10">H1</emphasis>
|
||
was divided by preparative TLC (cHx–Et
|
||
<subScript id="6B3F9B11D132FFEAFD4DF9E6FD52F9EA" attach="both" box="[724,733,1644,1658]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 95:5, × 2) into two alkaloidal zones, which after purification by TLC (EtOAc–ACN–TFAA, 40:10:0.1, × 3; and
|
||
<emphasis id="C5CF4546D132FFEAFE77F917FD8FF920" bold="true" box="[494,512,1693,1712]" italics="true" pageId="9" pageNumber="10">n-</emphasis>
|
||
Hx–EtOAc–Et
|
||
<subScript id="6B3F9B11D132FFEAFDE7F92EFD08F922" attach="both" box="[638,647,1700,1714]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 30:11:1, × 2) led to the isolation of aspidofractinine (
|
||
<emphasis id="C5CF4546D132FFEAFD81F933FDBEF95C" bold="true" box="[536,561,1721,1740]" pageId="9" pageNumber="10">18</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFDA7F933FD00F95C" box="[574,655,1721,1740]" metricMagnitude="-5" metricUnit="kg" metricValue="3.71" pageId="9" pageNumber="10" unit="mg" value="37.1">37.1 mg</quantity>
|
||
) and ()-2- ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1
|
||
<emphasis id="C5CF4546D132FFEAFE57F95FFE52F978" bold="true" box="[462,477,1749,1768]" italics="true" pageId="9" pageNumber="10">H</emphasis>
|
||
-indole (
|
||
<emphasis id="C5CF4546D132FFEAFDADF95FFDC2F978" bold="true" box="[564,589,1749,1768]" pageId="9" pageNumber="10">19</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFDF8F95FFD36F978" box="[609,697,1749,1768]" metricMagnitude="-5" metricUnit="kg" metricValue="2.75" pageId="9" pageNumber="10" unit="mg" value="27.5">27.5 mg</quantity>
|
||
). From subfraction
|
||
<emphasis id="C5CF4546D132FFEAFF4DF97BFF7EF894" bold="true" box="[212,241,1777,1796]" pageId="9" pageNumber="10">H2</emphasis>
|
||
, treated by multiple preparative TLC (cHx–Et
|
||
<subScript id="6B3F9B11D132FFEAFD07F972FD28F896" attach="both" box="[670,679,1784,1798]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 95:5, × 3; and cHx–LPE–Et
|
||
<subScript id="6B3F9B11D132FFEAFEB3F89EFEBCF8B2" attach="both" box="[298,307,1812,1826]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 80:20:4, × 3), 14,15-dihydrovindolinine (
|
||
<emphasis id="C5CF4546D132FFEAFD7AF886FD73F88F" bold="true" box="[739,764,1804,1823]" pageId="9" pageNumber="10">20</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFFFDF8A2FF39F8AC" box="[100,182,1832,1852]" metricMagnitude="-5" metricUnit="kg" metricValue="6.56" pageId="9" pageNumber="10" unit="mg" value="65.6">65.6 mg</quantity>
|
||
) was obtained. Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFE50F8A2FE69F8AB" bold="true" box="[457,486,1832,1851]" pageId="9" pageNumber="10">H3</emphasis>
|
||
was eventually merged with subfraction
|
||
<emphasis id="C5CF4546D132FFEAFF4FF8CEFF7FF8C7" bold="true" box="[214,240,1860,1879]" pageId="9" pageNumber="10">E3</emphasis>
|
||
. Subfraction
|
||
<emphasis id="C5CF4546D132FFEAFEEBF8CEFE00F8C7" bold="true" box="[370,399,1860,1879]" pageId="9" pageNumber="10">H4</emphasis>
|
||
was separated by preparative TLC (
|
||
<emphasis id="C5CF4546D132FFEAFD69F8CFFC8DF8C8" bold="true" box="[752,770,1861,1880]" italics="true" pageId="9" pageNumber="10">n-</emphasis>
|
||
Hx–Et
|
||
<subScript id="6B3F9B11D132FFEAFF04F8EDFF29F8E5" attach="both" box="[157,166,1895,1909]" fontSize="6" pageId="9" pageNumber="10">2</subScript>
|
||
NH, 90:10, × 3) into strictamine (
|
||
<emphasis id="C5CF4546D132FFEAFE66F8EAFD97F8E3" bold="true" box="[511,536,1888,1907]" pageId="9" pageNumber="10">21</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFDB0F8EAFDF3F8E3" box="[553,636,1888,1907]" metricMagnitude="-5" metricUnit="kg" metricValue="8.93" pageId="9" pageNumber="10" unit="mg" value="89.3">89.3 mg</quantity>
|
||
) and another alkaloidal zone, which after purification by TLC (CHCl
|
||
<subScript id="6B3F9B11D132FFEAFDE7F809FD08F801" attach="left" box="[638,647,1923,1937]" fontSize="6" pageId="9" pageNumber="10">3</subScript>
|
||
–ACN–TFAA, 40:10: 0.1, × 1) yielded 5-oxoaspidofractinine (
|
||
<emphasis id="C5CF4546D132FFEAFD84F812FDB9F83B" bold="true" box="[541,566,1944,1963]" pageId="9" pageNumber="10">22</emphasis>
|
||
,
|
||
<quantity id="304334B1D132FFEAFDD8F812FD0AF83B" box="[577,645,1944,1963]" metricMagnitude="-6" metricUnit="kg" metricValue="3.8" pageId="9" pageNumber="10" unit="mg" value="3.8">3.8 mg</quantity>
|
||
). Purification
|
||
</paragraph>
|
||
</subSubSection>
|
||
<subSubSection id="BFA1CADFD132FFEAFCABFE2AFAFEF82E" pageId="9" pageNumber="10" type="description">
|
||
<paragraph id="F7049954D132FFEAFCABFE2AFC77FE23" blockId="9.[818,1016,416,435]" box="[818,1016,416,435]" pageId="9" pageNumber="10">
|
||
<heading id="AC4C2E38D132FFEAFCABFE2AFC77FE23" bold="true" box="[818,1016,416,435]" fontSize="36" level="1" pageId="9" pageNumber="10" reason="1">
|
||
<emphasis id="C5CF4546D132FFEAFCABFE2AFC77FE23" bold="true" box="[818,1016,416,435]" italics="true" pageId="9" pageNumber="10">4.4. Biological assays</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCABFE52FBF3FE7A" blockId="9.[818,1148,471,491]" box="[818,1148,471,491]" pageId="9" pageNumber="10">
|
||
<heading id="AC4C2E38D132FFEAFCABFE52FBF3FE7A" bold="true" box="[818,1148,471,491]" fontSize="36" level="1" pageId="9" pageNumber="10" reason="1">
|
||
<emphasis id="C5CF4546D132FFEAFCABFE52FBF3FE7A" bold="true" box="[818,1148,471,491]" italics="true" pageId="9" pageNumber="10">4.4.1. Inhibition of hAChE, hBuChE</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCC8FE7EFCEBFDE7" blockId="9.[818,1487,500,631]" pageId="9" pageNumber="10">The activity of isolated alkaloids for the inhibition of human cholinesterases was assessed using the modified version of Ellman’ s method (Ellman et al., 1961), described recently (Al Mamun et al., 2020). The detailed description of the assay can be found in the Supplementary Data.</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCABFD11FB25FD3E" blockId="9.[818,1194,667,686]" box="[818,1194,667,686]" pageId="9" pageNumber="10">
|
||
<heading id="AC4C2E38D132FFEAFCABFD11FB25FD3E" bold="true" box="[818,1194,667,686]" fontSize="36" level="1" pageId="9" pageNumber="10" reason="1">
|
||
<emphasis id="C5CF4546D132FFEAFCABFD11FB25FD3E" bold="true" box="[818,1194,667,686]" italics="true" pageId="9" pageNumber="10">4.4.2. Kinetic study of hBuChE inhibition</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCC8FD3DFAE7FC92" blockId="9.[818,1487,695,770]" pageId="9" pageNumber="10">The pharmacokinetic study of the most active substance was evaluated with the same procedure as described recently (Hostalkova et al., 2019). The details can be found in the Supplementary Data.</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCABFCADFB9FFCAA" blockId="9.[818,1040,806,826]" box="[818,1040,806,826]" pageId="9" pageNumber="10">
|
||
<heading id="AC4C2E38D132FFEAFCABFCADFB9FFCAA" bold="true" box="[818,1040,806,826]" fontSize="36" level="1" pageId="9" pageNumber="10" reason="1">
|
||
<emphasis id="C5CF4546D132FFEAFCABFCADFB9FFCAA" bold="true" box="[818,1040,806,826]" italics="true" pageId="9" pageNumber="10">4.4.3. Inhibition of POP</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCC8FCC9FC5AFC1E" blockId="9.[818,1487,834,910]" pageId="9" pageNumber="10">For this assay, the same method was used as previously described (Al Mamun et al., 2020). The detailed protocol can be found in the Supplementary Data.</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCABFC38FBA1FC55" blockId="9.[818,1487,946,1049]" box="[818,1070,946,965]" pageId="9" pageNumber="10">
|
||
<heading id="AC4C2E38D132FFEAFCABFC38FBA1FC55" box="[818,1070,946,965]" fontSize="8" level="3" pageId="9" pageNumber="10" reason="8">
|
||
<emphasis id="C5CF4546D132FFEAFCABFC38FBA1FC55" box="[818,1070,946,965]" italics="true" pageId="9" pageNumber="10">
|
||
<emphasis id="C5CF4546D132FFEAFCABFC38FBABFC55" bold="true" box="[818,1060,946,965]" italics="true" pageId="9" pageNumber="10">4.4.4. Inhibition of GSK-3</emphasis>
|
||
β
|
||
</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCC8FC44FBFCFB89" blockId="9.[818,1487,946,1049]" pageId="9" pageNumber="10">The method for this biological test was performed according to the earlier study (Hulcova et al., 2018). Details of the procedure can be found in the Supplementary Data.</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCABFBB4FB3DFBFC" blockId="9.[818,1481,1085,1105]" lastBlockId="9.[818,1487,1113,1217]" pageId="9" pageNumber="10">
|
||
<emphasis id="C5CF4546D132FFEAFCABFBB4FB3DFBFC" bold="true" italics="true" pageId="9" pageNumber="10">
|
||
<heading id="AC4C2E38D132FFEAFCABFBB4FA46FBC0" bold="true" box="[818,1481,1085,1105]" centered="true" fontSize="36" level="1" pageId="9" pageNumber="10" reason="1">4.4.5. CNS penetration: In vitro parallel artificial membrane permeability</heading>
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||
<heading id="AC4C2E38D132FFEAFCABFBD0FB3DFBFC" box="[818,1202,1113,1133]" fontSize="8" level="3" pageId="9" pageNumber="10" reason="8">assay (PAMPA)-blood brain barrier (BBB)</heading>
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||
</emphasis>
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCC8FBFFFC76FB51" blockId="9.[818,1487,1113,1217]" pageId="9" pageNumber="10">The same procedure was used as in our previous report (Cahlikova et al., 2015; Panek et al., 2017). Details of the study are available in the Supplementary Data.</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCABFB7BFC6FFA94" blockId="9.[818,992,1265,1284]" box="[818,992,1265,1284]" pageId="9" pageNumber="10">
|
||
<heading id="AC4C2E38D132FFEAFCABFB7BFC6FFA94" bold="true" box="[818,992,1265,1284]" fontSize="36" level="1" pageId="9" pageNumber="10" reason="1">
|
||
<emphasis id="C5CF4546D132FFEAFCABFB7BFC6FFA94" bold="true" box="[818,992,1265,1284]" italics="true" pageId="9" pageNumber="10">4.5. Docking study</emphasis>
|
||
</heading>
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCC8FAA3FBE2F9A7" blockId="9.[818,1488,1321,1982]" pageId="9" pageNumber="10">
|
||
Molecular docking was used for binding poses calculations. The 3D structure ligands were built by OpenBabel, v. 2.3.2 (O’ Boyle et al., 2011) and optimized by Avogadro, v. 1.2.0 using the force fields GAFF (Hanwell et al., 2012). They were converted into pdbqt-format by OpenBabel, v. 2.3.2. The
|
||
<emphasis id="C5CF4546D132FFEAFC33FA12FC3AFA3B" bold="true" box="[938,949,1432,1451]" italics="true" pageId="9" pageNumber="10">h</emphasis>
|
||
BuChE structure was gained from the RCSB database (PDB ID: 4BDS, resolution 2.10 Å) and prepared for docking by the function DockPrep of the software Chimera, v. 1.14 (Pettersen et al., 2004) and by MGLTools, v. 1.5.4 (Morris et al., 2009). The docking calculation was made by Vina, v. 1.1.2 as semi-flexible with flexible ligand and rigid receptor (Trott and Olson, 2010).
|
||
</paragraph>
|
||
<paragraph id="F7049954D132FFEAFCC8F9CAFAFEF82E" blockId="9.[818,1488,1321,1982]" pageId="9" pageNumber="10">
|
||
The docking pose of
|
||
<emphasis id="C5CF4546D132FFEAFB87F9CAFBB8F9C3" bold="true" box="[1054,1079,1600,1619]" pageId="9" pageNumber="10">19</emphasis>
|
||
was improved by MD simulation. The receptor structure was prepared using the software Chimera. The bestscored docking pose was taken as the initial for MD. The force-field parameters for ligands were assessed by Antechamber (Wang et al., 2006), v. 20.0 using General Amber force-field 2 (Wang et al., 2004). MD simulation was carried out by Gromacs, v. 2018.1 (Abraham et al., 2015). The complex receptor-ligand was solvated in the periodic water box using the TIP3P model (Mark and Nilsson, 2001). The system was neutralized by adding Na
|
||
<superScript id="00CE341CD132FFEAFB82F891FBAAF8B7" attach="left" box="[1051,1061,1819,1831]" fontSize="6" pageId="9" pageNumber="10">+</superScript>
|
||
and Cl ions to a concentration of 10 nM. The system energy was minimalized and equilibrated in a 100-ps isothermal-isochoric NVT and then a 100-ps isothermal-isobaric NPT phase. Then, a 10-ns MD simulation was run at a temperature of 300 K. The molecular docking and MD results were 3D visualized by the PyMOL Molecular Graphics System, Version 2.4.1, Schr¨odinger, LLC.
|
||
</paragraph>
|
||
</subSubSection>
|
||
</treatment>
|
||
</document> |