Discovery Of Structurally Diverse Diterpenoids And Their Bioactivity

Natural products are one of the important sources of innovative drugs,drug candidate and lead compounds as they usually possess novel structures and various activities.Diterpenoids are one of the most abundant and most important active components in traditional Chinese medicines.Many famous diterpenoids such as taxol,guan-fu base A,ginkgolides and andrographolides showed excellent biological activities,therefore,diterpenoids have become a hotspot in the field of natural medicine research.Herein,we investigated four medicinal plants,Croton crassifolius Geisel.,Scutellaria barbata D.Don,Sigesbeckia pubescens L.and Vitex rotundifolia L.,which are rich in diterpenoids components.As a result,a total of 108 compounds were isolated from the extracts of the four plants by using modern column chromatography,such as Chromatorex C18,Chromatorex C8,MCI gel CHP-20 P,TSK gel Toyopearl HW-40 F,Sephadex LH-20,silica gel and semi-preparative HPLC.Their structures were elucidated on the basis of extensive spectroscopic means,X-ray single crystal analysis,and hydrolysis methods.Among them,there are 86 diteerpenoids and 33 compounds are new compounds,including various diterpenoids,sesquiterpenoid glycosides,lignans and flavonoids.Some of them showed good activities according to folk application and various bioactivity screening models.Nineteen new compounds,including eighteen diterpenoids(1-18)and one sesquiterpenoid glycoside(43),along with thirty-eight known compounds were isolated from the roots of C.crassifolius Geisel.Compounds 1-4 were ring B or A rearranged diterpenoids.Compound 18 was a rare trachylobane diterpenoid.Compound 43 was a sesquiterpenoid glycoside,which is the first report about the sesquiterpenoid glycoside from C.crassifolius.Six new neo-clerodane diterpenoids(58-63)and four known analogues were isolated from the aerial parts of S.barbata.Compounds 61-63 were spiroclerodane diterpenoidsFive new compounds,including two ent-kaurane diterpenoids(68-69),one ent-pimarane diterpenoid(79),one lignans(91)and one flavon dimers(92),together with twenty known compounds were isolated from the aerial parts of S.pubescens.The absolute configurations of compounds 68-69 and79 were determined by single-crystal X-ray diffraction analysis.Phytochemical investigation on the fruits of Vitex rotundifolia led to the isolation and identification of sixteen compounds,three of which were new labdane diterpenoids(93-94 and 96).Further pharmacologic study of the isolated diterpenoids showed that compounds 9/10,20,22,63,66 and 74 showed cytotoxic activities with IC50 values range from 5.2 to 32.7?M.Compounds 19 and 39 showed moderate effects of lowering lipid by DiI-LDL uptake test.