Structural Modification Of Piscidinol A And Quality Control Of Shansarian Rind

The acquired immune deficiency syndrome(AIDS)is one of the most dangerous infectious diseases which is caused by Human immunodeficiency virus.The HIV-1 protease was an essential part of the material in HIV life cycle,as well as has been used a promising target for screening anti-AIDS drugs.Previously dammarane-type tetracyclic triterpene derivatives and A-seco triterpenes were found to be good inhibitors against HIV-1 protease by our research group.The synthesis of Piscidinol A derivatives and evaluation of their anti-HIV-1 protease activity will be introduced in this work.By using oxidation and substitution reactions,Piscidinol A was synthesized on hydroxyl groups on C-17 side chain and carbonyl on C-3.15 Piscidinol A derivatives were synthesized succefully including,two A-ring modified derivatives,mono-acylated(3-OH),biacylated(23,24-bihydroxyl)and multiacylated(3,23,24-or 23,24,25-trihydroxyl)derivatives were synthesized.Their structures were identified by MS and NMR data.To investigate the inhibition of Piscidinol A derivatives against HIV-1 protease by fluorescence method,A-seco derivative lb(IC50 = 38.2?M)was moderately inhibitor of HIV PR and the compound 4b,6a,and 7b(50<IC50<100 ?M)were more inhibitory against HIV-1 PR than the others.Hepatitis C is a chronic infectious disease which is caused by the hepatitis C virus.About 40 million people lived with hepatitis C in China.HCV NS3A/4A serine protease play a key role in the viral non-structural proteins and ripening process,which is one of the important targets for screening anti-HCV drugs.Three natrual products,daphnetin,daphneticin and 7-Hydroxy-8-methoxycoumarin isolated from Daphne papyracea Wall.ex Steud.var.crassiuscula Rehd.showed anti-HCV NS3/4A protease activity.Only a little literatures were repoted the quality control and fingerprint establishing of D.papyracea Wall.ex Steud.var.crassiuscula Rehd.,and it will be introduced in this work.In this paper,D.papyracea Wall.ex Steud.var.crassiuscula Rehd.from different places of GuiZhou province had been analyzed by a series of methods.First,some pharmacognostic identification have been carried out,for example medicinal herbs traits,microscopic characteristics and TLC,which can provide theory basis for identification of this drug rapidly.Second,the examination projects of moisture,water dissolved substances and ethanol-soluble extractives were detected on the 17 batches medicinal.The results of moisture,water dissolved substances and ethanol-soluble extractives are between 6.95%?12.01%,8.0%?14.02%,16.13%?26.67%.Third,the contents of daphnetin,daphneticin and 7-hydroxy-8-methoxycou-marin have been measured with HPLC among the samples from different regions.As results,the rang of concent of daphnetin is from 113.9 pg/g to 4826.7 ?g/g;the rang of concent of daphneticin is from 125.0 ?g/g to 665.0 ?g/g and the rang of concent of 7-hydroxy-8-methoxycoumarin is from 41.4 p.g/g to 330.7 ?g/g.Meanwhile,the fingerprints of D.papyracea Wall.ex Steud.var.crassiuscula Rehd.have been established,which can be used to evaluate the quality of it.The fingerprints of the 10 batches of medicinal materials showed that 13 main common peaks have been set up.