Phytochemistry of the genus Skimmia (Rutaceae) Author Epifano, Francesco Dipartimento di Farmacia, Università ‘‘ G. D’Annunzio’ ’ Chieti-Pescara, Via dei Vestini 31, 66013 Chieti Scalo, CH, Italy Author Fiorito, Serena Author Genovese, Salvatore Author Granica, Sebastian Author Vitalini, Sara Author Zidorn, Christian text Phytochemistry 2015 2015-07-31 115 1 27 43 http://dx.doi.org/10.1016/j.phytochem.2015.02.014 journal article 285349 10.1016/j.phytochem.2015.02.014 d30e1c4c-6a0f-4e42-97ec-8f9abb4e26ea 1873-3700 10486867 3.5. S. laureola S. laureola (syn. Limonia laureola Blanco ) is an evergreen shrub, native to Northern China and the Northern Himalayan region often cultivated for ornamental purposes, also as a bonsai ( He et al., 1995 ). Leaves are consumed, after having been cooked, as a condiment in curries or as flavouring for other food by local populations in China and Himalayan region. Fresh leaves were used in the treatment of smallpox and smoke produced by burning the leaves is believed to purify the air ( He et al., 1995 ). Together with S. japonica , S. laureola is the phytochemically and pharmacologically most intensely studied species of the genus Skimmia . S. laureola is a rich source of coumarins, alkaloids, triterpenes, and steroids and contains essential oil. The first alkaloid isolated from S. laureola subsp. multinervia was evoxine 17 ( He et al., 1995 ). Atta-ur-Rahman et al. (1998a ,b) obtained four quinolone alkaloids from the ethanolic extract of leafy shoots and named them ptelefoliarine 6 , acetoxyptelefoliarine 7 , acetoxyedulinine 8 , and orixiarine 9 , and methyl isoplatydesmine 20 . Moreover, two additional quinoline alkaloids, acetyl ribalinine 10 and ribaliprenylene 11 were isolated ( Sultana et al., 2005 ). In 2007 the same group provided evidence for the presence of yet two additional quinoline alkaloids in addition to 6–8 , and 11 , methyl isoplatydesmine 20 and dictamnine 12 were isolated from aerial parts ( Sultana et al., 2007 ). The first study describing the isolation and structural characterization of coumarins was published by Chatterjee and Bhattacharyya in two different papers in 1947 and 1953; leaves and bark yielded three coumarins, umbelliferone 21 , O O β−D-glucopyranosyl H H COOH O O82 , limonin, MW 470 83 , limonin 17-β−D-glucopyranoside, MW 650 84 , isoobacunoic acid, MW 472 β−D-glucopyranosyl HO O O COOH O O OHO O 87 , methyl isoobacunoate diosphenol 85 , cyclocalamin,MW 502 86 , cyclocalamin 17-β−D-glucopyranoside, MW 682 R = CH 3, MW 502 88 , isoobacunoate acid diosphenol R = H, MW 486 β−D-glucopyranosyl O COOH O OOO89 , nomilin 17-β−D-glucopyranoside, R = acetyl MW 694 91 , nomilin, R = acetyl MW 514 90 , desacetylnomilin 17-β−D-glucopyranoside, R = H, MW 652 92 , desacetylnomilin,R = H, MW 472 93 , obacunone, MW 454 β−D-glucopyranosyl β−D-glucopyranosyl O O COOH COOH O O O OO O 95 , retrocalamin, MW 462 96 , retrocalamin 17-β−D-glucopyranoside, MW 94 , obacunone 17-β− D-glucopyranoside, MW 652 642 β−D-glucopyranosyl COOH O HO HO O OOH O 97 , ichangensin, MW 444 98 , ichangensin 17-β−D-glucopyranoside, MW 624 99 , calamin, MW 520 isopimpinellin 62 , and bergaptene 46 . The same research group isolated scopoletin 24 as an additional compound from an ethanol extract of the bark ( Bhattacharjee and Mullick, 1960 ) . The same four coumarins were also obtained from apolar extracts of dry leaves ( Pathak and Pant, 1972 ; Bhargava and Seshadri, 1973 ). Investigations of roots extract of S. laureola afforded two additional coumarins, namely (+)-heraclenin 60 and isoimperatorin 47 , along with the glucoside of umbelliferone (skimmin) 22 and scopoletin 24 ( Sood et al., 1978 ). Other coumarins, namely 7-methoxy-6-(2 0 - methoxy-3 0 -hydroxy-3 0 -methylbutyl)-coumarin 28 , isogospherol 59 , heraclenol 61 , 5,8-dimethoxycoumarin 35 , 7-methoxy-6-[2 0 - oxo-3 0 -methylbutyl]-coumarin 29 , ulopterol 27 , and marmesin 52 were isolated from leaves ( Atta-ur-Rahman et al., 2002 ; Sultana et al., 2004 ). Fig. 8. Chemical structures and molecular weights of triterpene type limonoids detected in seeds of Skimmia japonica – compounds 82–102 . Fig. 9. Chemical structures and molecular weights of compounds 103 and 104 . S. laureola was also shown to be a rich source of triterpenes. The first phytochemical report concerning these secondary metabolites was O -methyllaureolol 74 ( Zhang et al., 1995 ). Further details about the exact configuration were given by the same group two years later ( Zhang et al., 1997 ). Atta-ur-Rahman et al. (1998b) obtained 3-oxo-lanosta-20-25-diene-3-one 73 from aerial parts of S. laureola . A series of other penta- and tetracyclic triterpenes were isolated in the following years: taraxerone 81 ( Parvez et al., 1999 ), O -methylcyclolaudenol 76 was obtained from the leaves and described by Atta-ur-Rahman et al. as well as by Hussain et al. in a number of reports published between 2002 and 2009. A derivative of the latter compound, namely 16,29-dihydroxy-20- ene-cyclolaudenol 77 has been isolated in 2008 by Sultana et al., and finally 24-methyllanosta-7,25-dien-3-one 75 was obtained by Hussain and Parvez (2010) . The first investigation of S. laureola essential oil was published in 1920 by Anon who reported some chemo-physical parameters (density, optical rotation, and solubility) of the essential oil obtained by steam distillation of the leaves. The chemical composition of the essential oil prepared from the same source was found to consist mainly of linalool and its acetate with smaller quantities of undefined sesquiterpenes ( Simonses, 1921 ). The composition of the essential oil of the leaves of S. laureola was later refined in terms of percentages and phytochemicals in 1936 by Wienhaus and Rajdhan. These authors recorded the further presence of αpinene, β- phellandrene, azulene, and bergaptene. In 1966 Sharma et al. found geraniol, citronellyl formate, myrcene, methyl heptenone, nerol, citronellyl isobutirate, and citral as additional components. In 1972 Pathak and Pant revealed the presence of phenyl isobutyrate, camphene and furfural; these results were confirmed by Sarin (1977) and Razdan et al. (1980) . In 1989 Goel et al. identified citronellol as an additional component; and in 1992 Mathela et al. stated that pregeijerene and geijerene could be the most important compounds for the typical aroma of the essential oil of leaves of S. laureola . In 2003 Shah et al. determined the seasonal variation of the proportions of linalool (ranging from 4% to 28%) and linalyl acetate (ranging from 37% to 64%) in the essential oil. In 2010 Jangwan et al. identified α- terpineol and geranyl acetate as additional components. Shah et al. (2012) compared results of the quali-quantitative analysis of essential oil by ‘‘classic’’ hydro-distillation and head space-solid phase micro extraction; the main differences were observed in the percentages of linalool and its acetate, α- pinene, β- phellandrene, α- terpineol, and geyrene. Seeds of S. laureola were shown to be a rich source of polyunsaturated fatty acids: the apolar extract, analyzed by GC–MS after derivatization as methyl esters, afforded the following percentages of the respective acids: palmitic 8.28%, stearic 1.47%, palmitoleic 2.57%, oleic 33.41%, linoleic 31.15%, and linolenic 23.12% ( Pasha et al., 1966 ). Skimmidiol fatty acid ester 104 was isolated from aerial parts ( Sultana et al., 2005 ) and the similar compound skimmilaureol 103 was isolated from leaf extracts by Sultana et al. (2008) .