Studied On Chemical Components Of Xylocarpus Granatum Seeds And Pericarps, And Semi-synthesis Of The Active Components In Inula Britannica L

Part one Chemical study on the components of Xylocarpus granatumseedsThe genus Xylocarpus, distributed widely in the coastal areas of South-East Asia, Australia, East Africa, and Indian Ocean, comprises only threespecies of the Meliaceae family. Xylocarpus granatum Koenig and Xylocarpusmoluccensis （Lam） are the most popular plants in empirical study, and arefound to be rich in limonoids. The mangrove plant X. granatum Koenig isused as a folk medicine in Southeast Asia and Indian for the treatment ofdiarrhea, cholera, and fever diseases such as malaria, and also as anantifeedant. Since the first limonoid, gedunin, was reported from this plant, theunique structural patterns of limonoids have attracted considerable attentionfrom medicinal chemists as well as chemical biologists because of theirfascinating structural diversity and wide spectral of biological activities. As aresult, more than50limonoid derivatives have been isolated from X. granatum,and they have been classified into phragmalin-, mexicanolide-, obacunol-, andandirobin-types. Recently, much attention has been paid to Xylocarpus speciesdue to limonoids with unique C-skeletons and their tumor cytotoxic activities.Objective: To study the components in seeds of X. granatum, manymethods are used in the isolation and purification of the components. Thestructures of the pure compounds were elucidated by means of HR-ESI-MS,¹H NMR,¹³C NMR,¹H-¹H COSY, HMQC and HMBC, etc. To exploid theactive constituents for tumor cells by activity screen.Methods: Dried seeds （21kg） of X. granatum were extracted with95%ethanol at room temperature. After evaporation of the solvent under reducedpressure, the residue was suspended in water and extracted with petroleum ether, dichloromethane and ethyl acetate in order, successively. The isolationand purification were carried out by silica gel column chromatography,Sephadex, preparative TLC and preparative HPLC. The structures of theisolated compounds were identified with the help of HR-ESI-MS,¹H NMR,¹³C NMR,¹H-¹H COSY, HMQC and HMBC techniques.Results: Forty-eight compounds were isolated and elucidated from theseeds of X. granatum, their structures were identified as:9-trans-hexadecenoic acid （1）, stigmasterol （2）,3-oxo-4,22-choladienicacid （3）, grantumin C （4）, xylocarpin H （5）, xylomexicanin A （6）, cipadesin A（7）, xyloccensin K （8）, piscidinol G （9）, xylogranatin C （10）,hainangranatumin C （11）, xylogranatin D （12）, xylocartin S （13）, xylocartin A（14）, xylocartin B （15）, hainangranatumin A （16）, xylocarpin G （17）,hydroxydammarenone-â…¡ （18）, xylocartin T （19）, xylocartin N （22）, xylocartinO （25）, febrifugin （26）, tigloylseneganolide A （27）, khaysin T （28）, cipadesin（29）, granatumin B （30）, xylocartin M （32）, xylocartin C （37）,bis（2-ethylhexyl） phthalate)（38）, xylocartin E （40）, xylocartin D （41）,xylocartin Q （44）, xylocartin R （46）, xylocartin F （47）, xyloccensin S （48）,granaxylocarpin C （54）, xylogranatin E2（56）, xylocartin P （60）, xylocartin J（62）, xyloccensin Q （64）, xylocartin K （65）, xylocartin G （67）, xyloccensin P（68）, xylocartin H （72）, cedrodorin （73）, xylorumphiins D （75）, xylocartin L（77）, xylocartin I （79）。Conclusion: We investigated the constituents of the seeds of X. granatum,48compounds were isolated and elucidated, and among them xylocartins A-Twere20new compounds.Part Two Chemical study on the components of Xylocarpus granatumpericarpsObjective: To study the components in pericarps of X. granatum, manymethods are used in the isolation and purification of the components. Thestructures of the pure compounds were elucidated by means of HR-ESI-MS,¹H NMR,¹³C NMR,¹H-¹H COSY, HMQC and HMBC, etc. To identify active constituents by activity screen.Methods: Dried pericarps （13kg） of X. granatum were extracted with95%ethanol at room temperature. After evaporation of the solvent underreduced pressure, the residue was suspended in water and extracted withpetroleum ether and dichloromethane, successively. The isolation andpurification were carried out by silica gel column chromatography, Sephadex,preparative TLC and preparative HPLC. The structures of the compoundswere elucidated with the help of HR-ESI-MS,¹H NMR,¹³C NMR,¹H-¹HCOSY, HMQC and HMBC techniques.Results: Four compounds were isolated and elucidated from thepericarps of X. granatum: β-sitosterol （1）,3-oxo-4,22-choladienic acid （2）,xylocarpin H （3）, xyloccensin K （4）Conclusion: The constituents of the pericarps of X. granatum wereinvestigated, four compounds were isolated and elucidated, among them3-oxo-4,22-choladienic acid （2） was found from this genus for the first time.Part three Preparation of ABL by SFE and semi-synthesis of derivativesof ABLObjective: To extract the active component ABL from Inula britannica Lby SFE with optimized conditions. The extraction was isolated to obtain ABL,which was used to synthesize the active derivatives.Methods: Air-dried flowers of Inula britannica L （10Kg） were extractedby SFE, which conditions were optimized to obtain the extraction （355g）. Theextraction were isolated and purified by silica gel chromatography to obtainABL, which was used to synthesize the active derivatives NABL. Theanti-tumor activities were screened on many cell lines.Results: The optimized conditions of SFE was temperature:60℃,pressure:25.0Mpa, flow rate of CO₂:10L/min.40g NABL were synthesized,which anti-tumor activities were better than Cisplatin to HT-29, K111, L1210and3LL cell lines.Conclusion: This research work established the method to used SFE to extract the active component ABL from Inula britannica L. The derivativeNABL was used to do the further investigation on in vivo pharmacologyexperiments.