Research Of Diterpenoids Activating Latent HIV From Buds Of Wikstroemia Chamaedaphne Meisn.

HIV latency is a major obstacle to the cure of AIDS,and the discovery of highly potent latent activating agents and new activation mechanisms is the key point to remove this barrier.Many literature showed that diterpenoid compounds have the effect of activating latent HIV.The dried buds of the Wikstroemia chamaedaphne Meisn.distributed in Shanxi Province in China was studied in this thesis.We used silica gel column chromatography,ODS column chromatography,gel Sephadex column chromatography,HPLC preparation and semi-preparative separation method to isolate 27 compounds from the buds of the Wikstroemia chamaedaphne Meisn..Their chemical structures were determined by infrared spectroscopy,ultraviolet spectroscopy,mass spectrometry,nuclear magnetic resonance and other methods.The nine diterpenoids isolated from buds of the Wikstroemia chamaedaphne Meisn.were compound 1,compound 2,pimelea factor S6(3),pimelea factor S7(4),pimelea factor P2(5),pimelea fctor P3(6),6?,7?-epoxy-5?-hydroxy-12-deoxyphorbol 13-decanoate(7),simplexin(8),daphnetoxin(9),and 18 other compounds isolated as stigmasterol(10),7?-hydroxysitosterol 3-O-?-D-glucoside(11),daucosterol(12),progesterone(13),hydroxyacorenone(14),(6S,9S)-roseoside(15),(-)-nortrachelogenin(16),(+)sesamin(17),(-)-syringaresinol(18),(+)-Lariciresinol(19),secoisolariciresinol(20),(+)-isolariciresinol(21),?-sitosterol(22),medioresinol(23),matairesinol(24),chrysoeriol 4'-O-?-D-glucopyranoside(25),kaempferol 3-O-?-D-glucopyranoside(26),luteolin-4'-O-?-glucopyranoside(27).Among them,the compounds 1-3 have not been reported,and in addition,the compounds 7,10-16,18-20,22-26 were isolated from this plant for the first time.The diterpenoids isolated in our laboratory before were tested for cell-level activity using J-Lat cell model.The results showed that compounds2,3,5-8 showed significant activity in activating latent HIV,in whichcompound 3 showed an activation rate of 51.97% at a concentration of 160 n M,and its activation was greater than the effect of positive control compound Prostratin.Further,based on the obtained activity results,the structure-activity relationship of diterpenoids was preliminarily discussed,and the constituent groups affecting HIV activation activity were preliminarily inferred.