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 3.4. S. japonica Fig. 4. Chemical structure and molecular weights of angular coumarins – compounds 64 and 65. S. japonica is an evergreen plant native to the Himalaya and East Asia . In Europe it is widely cultivated as an ornamental plant featuring large white fragrant inflorescences ( Taylor, 1987 ). The first phytochemical study on S. japonica was reported at the beginning of XXth century. Honda (1904) isolated the alkaloid skimmianine 13 from an ethanol extract of S. japonica leaves but at the time was neither able to determine its exact chemical structure nor to assign a correct molecular formula. In the early 1930s Asahina and Inubuse (1930) repeated the work of Honda, re-isolated skimmianine 13 and, using classical methods of synthetic organic chemistry in combination with the analytical methods available at the time, correctly identified its structure 13 as a dimethoxy derivative of dictamnine 12 . Later Tomita and Ishii (1958) re-examined the alkaloid content of S. japonica and showed that apart from skimmianine 13 , which is the major alkaloid occurring in S. japonica extracts, the species also contained other alkaloids of at the time not fully confirmed structure. In the 1960s Boyd and Grundon (1967) studied female plants of S. japonica and isolated apart from skimmianine 13 two additional alkaloids, dictamnine 12 and (+)-platydesmine salt 19 . In 1970 and 1974 the same team expanded the knowledge on the occurrence of alkaloids in leaves of S . japonica by describing the isolation and identification of eduline 3 , γ- fagarine 14 , and 5-hydroxy-1-methyl-2-phenyl-4-quinolone 1 ( Boyd and Grundon, 1970 ; Grundon et al., 1974 ). Fig. 5. Chemical structures and molecular weights of flavonols and flavones detected in Skimmia species – compounds 66–69 . Fig. 6. Chemical structures and molecular weights of flavanones in Skimmia species – compounds 70–71 . Several studies have been carried out focusing on the biosynthesis and chemical transformations of alkaloids occurring in S. japonica and other taxa of the Rutaceae family ( Ohta, 1953 ; Tomita and Ishii, 1958 ; Matsuo and Kasida, 1966 ; Collins and Grundon, 1969 ; Boyd and Grundon, 1970 ; Grundon and James, 1971 ; Collins et al., 1974 ; Grundon et al., 1974 ). Apart from alkaloids, S . japonica is a rich source of coumarins, which are the second major group of compounds present in this genus. The first report on the occurrence of coumarins stems from 1938 when seselin 65 was isolated ( Späth and Neufeld, 1938a ). Additional investigations by the same authors revealed that apart from seselin, S. japonica contains high quantities of umbelliferone 21 and its glucoside – skimmin 22 ( Späth and Neufeld, 1938b ). Later Atkinson et al. (1974) showed that S. japonica is a source of both simple coumarins and furocoumarins, which has been confirmed by other studies ( Reisch and Achenbach, 1989 , 1991 , 1992a ,b). Reisch and Achenbach (1992a) reported on differences in the chemical composition of stem barks from male and female plants of S. japonica . The authors showed some differences in the content of simple coumarins between plants of both sexes and reported the occurrence of the following coumarins in S. japonica : 21 , 22 , 24 , 31 , 37–43 , 45–51 , 54–58 , 60–63 and 65 . Unfortunately, however, the results of this potentially very interesting study are difficult to critically evaluate, because the authors fail to report standard deviations for their quantification results and because it is not clear whether the reported values are derived from investigations of one single plant per sex or whether multiple samples had been investigated to obtain the reported results. Takeda (1941) investigated the alcoholic extract of S. japonica from which two triterpenoids – skimmion/taraxeron 81 and skimmiol/taraxerol 80 together with skimmianine were isolated and identified. The investigation of leaves and fruits of S. japonica has led to the isolation and identification of two more triterpenoids named skimmiarepins A and B 78 and 79 ( Ochi et al., 1988 ). The only steroid detected in S. japonica so far is β- sitosterol 72 ( Reisch and Achenbach, 1991 , 1992a ). Triterpenoids and steroids were reported to be minor compounds in S. japonica . In the literature there are several studies concerning the biosynthesis and transformations of triterpenoids from Skimmia ( Takeda and Yoshiki, 1941 ; Takeda, 1942 ; Takeda, 1943a ,b; Abe, 1962 ). Seeds of S. japonica yielded a wide variety of limonoids, a group of triterpenoids known from the Rutaceae and Meliaceae families. A total of 21 limonoids 82–102 including 13 aglycones belonging to the limonin, calamine, and ichangensin groups together with eight glucosides were detected and quantified in S. japonica by Hasegawa et al. (1998) . Chemical structures and molecular weights of these limonoids are displayed in Fig. 8 . The report of Hasegawa et al. (1998) is the only report on limonoids in the genus Skimmia so far. Though the authors claim to have used TLC and NMR (aglycones) and HPLC and NMR (glucosides) for compound identification, it is striking that they were able to identify so many compounds with a limited sample ( 200–250 g ) using these methods. It seems feasible that only few main compounds were actually identified by NMR while most minor compounds were only assigned using Rf values or HPLC retention times. This would also explain why no new compounds were amongst the 21 limonoids reported in this study. According to our literature survey neither qualitative nor quantitative modern chromatographic systems to analyse S. japonica extracts have been established. Notably, there are no studies on the presence of polyphenols (phenolic acids and flavonoids) in aerial parts of S. japonica . This β group of compounds seems to have been neglected so far and research focusing on the structures and yields of these compounds in S. japonica should be performed.