Studies On Chondria Crassicaulis And Aglaia Abbreviata:Chemistry And Bioactivities

Red alga Chondria crassicaulis belongs to the genus Chondria?family Rhodomalaceae,order Caremiales,class Rhodophyceae,and phylum rhodophyta?,found in all oceans and seas as well as almost all latitudes,mostly in tropical and subtropical regions.This alga has anti-tumor,anti-viral,anti-fungal,anthelmintic,and cytotoxic effects.Literature checking revealed that metabolites from this alga are alkanes,amino acids,unsaturated fatty acids,glycerides,and sterols.The plant Aglaia abbreviate belonging to the genus Aglaia?family Meliaceae?are mainly distributed in Sichuan,Yunnan,and Guangxi Provinces in China.This Aglaia species has been reported recently to contain many types of compounds,including terpenoids,bisamides,and pregnane steroids,etc,which have significant anti-tumor effects.During the course of our search for bioactive small molecular compounds,we have collected Chondria crassicaulis from Nanji Island Zhe Jiang Province and collected Aglaia abbreviate from Xishuangbanna Yunnan Province.In this thesis,we have systematically studied on the chemical constituents and biological activity of the two plants.The two biologic materials were exhaustively extracted with 95%EtOH.The resultant extracts were suspended in H₂O and then partitioned with ethyl acetate.The ethyl acetate-soluble portions were repeatedly subjected to silica gel and Sephadex LH-20 column chromatography followed by semipreparative C₁₈ silica HPLC purification,yielding 37 compounds,including 6 steroids,6 sesquiterpenes,3diterpenes,4 flavonoids,6 diphenylethenes,2 tocopherols,and 10 other types of compounds.Their structures including relative stereochemistry were elucidated on the basis of extensive spectroscopic analysis?NMR,MS,IR,UV,CD,and optical rotation?and comparison with those reported data in the literature.Among these compounds,8 new compounds were discovered.11 compounds,including 5 steroids?1-1¹-5?,a fatty acid?1-6??2 aliphatic ketones?1-7 and 1-8?,2 phthalates?1-9 and 1-10?,and a butenolide?1-11?,were isolated from Chondria crassicaulis.Among these compounds,compounds 1-7 and1-8 were identified as new molecules,and 1-7 is also structurally the dimer of 1-8.Surprisedly,these two new compounds are shown to be racemic,respectively,on the basis of their optical rotation,CD,and ECD calculation.Acordingly,the structures of compounds 1-7 and 1-8 were elucidated as 4,11-dihydroxy-4,11-dimethyltetradecane-2,5,10,13-tetraone?1-7?,7-butoxy-4-hydroxy-4-methylheptane-2,5-dione?1-8?.To the best of our knowledge,this is the first report of the discovery of such an aliphatic ketone.26 compounds,including 6 sesquiterpenes?2-1²-6?,3 diterpenes?2-7²-9?,4flavones?2-10²-13??6 prenylated diphenylethenes?2-14²-19??2 tocoperols?2-20 and 2-21?,2 steroids?2-22 and 2-23?,a bisamide?2-24?,a phthalate?2-25?,and a norsesquiterpenes?2-26?,were isolated from Aglaia abbreviate.Of these compounds,2-13,2-14,2-15,2-16,2-17,and 2-26 are new compounds,named as3?,6-dihydroxy-4?,7-dimethoxyisoflavone?2-13?,2,4-dihydroxy-6-?2-hydroxyphenethyl?-3-?3-methylbut-2-en-1-yl?-methyl benzoate?2-14?,2,2-dimethyl-2?,5-dihydrodroxy-7-?2phenylethyl?-chromene?2-15?,?E?-2-?6-hydroxy-3,7-dimethylocta-2,7-dien-1-yl?-3,5-dihydroxy-bibenzyl?2-16?,2-[?2E,5E?-7-hydroxy-3,7-dimethylocta-2,5-dien-1-yl]-3,5-dihydroxy-bibenzyl?2-17?,and?E?-4-?2,5,5-trimethylcyclopent-2-en-1-yl?but-3-en-2-one?2-26?,respectively.To our knowledge,this is the first report of the discovery of diphenylethenes and tocoperols from the genus Aglaia.The PTP1B inhibition,enzyme inhibition against receptor tyrosine kinases c-Met,ALK,and RET,and antifungal activity of secondary metabolites isolated from Chondria crassicaulis and Aglaia abbreviate were evaluated.At present,the evaluation of PTP1B inhibitory and enzyme inhibitory activities of the compounds from C.crassicaulis have been finished,while the antifungal activities of the compounds from C.crassicaulis is being assessed.As a result,only compound 1-5exhibited weak inhibitory activity against RET with an IC₅₀ value of 9.8?M.However,the antifungal,PTP1B inhibitory,and enzyme inhibitory activities of secondary metabolites from A.abbreviate are being assessed.