The Study On The Novel Synthetic Method For Chiral β-amino Acids And Asymmetric Total Sythesis Of Natural Product Curcumol

This thesis aims at the study on a new synthetic method for asymmetric synthesis of chiral β-amino acids and natural product curcumol.This dissertation consists of two parts as following:In the first section,we firstly reviewed the preparative method forβ-amino acid and its application in drug synthesis.Secondly,we investigated the asymmetric reduction of various enamine derivatives promoted by CBS-BH3 catalysis,which afforded a variety of chiralβ-amino acids in high stereoselectivity and moderate yield.We also systematically studied the effects of reaction conditions,such as various chiral amine auxiliary,amounts of CBS,reaction temperature,and reaction time on the yield and enantioselectivity.Furthermore,we used this method for the synthesis of(3R)-N-(tert-Butoxycarbonyl)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid,which is important intermediate of diabete drug sitagliptin.In addition,we have found that NaBH4/ZnI2 reagent could promote the reduction of the β-enamine with excellent yield and good stereoselectivity.Inspired by these results,we also investigated the asymmetric reduction of the β-enamine catalyzed by NaBH(OAc)3/MgI2 in acetonitrile as solvent.Intrestingly,the reduction of the β-enamine was efficiently carried out with the treatment of NaBH(OAc)3/MgI2 in nearly improved quantitative yield.We are focusing on the improvement of its stereoselectivity in our lab.In the second section,we reviewed the biological activity about the natural products of curcumol and other guaiane sesquiterpenes.Then the methodology for the synthesis of guaiane sesquiterpenes was reviewed as well.This thesis the first total synthesis of curcumol was developed from 3-butyne-1-alcohol as starting material.The chiral intermediate of weinreb amide was obtained in good yield through 10 steps.The key steps are the introduction of allenic functional groups and the chiral methylgroup with a high stereoselectivity,which provided the good basis for the construction of the skeleton of curcumol.All the compounds were confirmed by 1HNMR,13C NMR,MS and IR analysis.