Design,Synthesis And Application Of Gem-difluorocarba-sugar Glycosides

Fluorinated compounds play a crucial role in medicine,material,agrochemical and national defense industry due to their unique physicochemical properties and biological activities.The gem-difluoro-carbasugars not only retain the characteristic properties of carbohydrate,but also incorporate the unique function of fluorine atom?s?.Hence,it is of great demanding to establish an efficient method for the synthesis of gem-difluoro-carbasugar,and thus to facilitate the understanding of their chemical properties and the potential applications.This thesis is accordingly divided into three parts,including molecular docking,synthetic method,and application development of gem-difluoro-carbasugars.In Chapter one,DFT?Discrete Fourier Transform?computational results indicated that gem-difluoro-carbasugar,whose endocyclic oxygen atom has been replaced by a gem-difluoromethyl group,does not affect carbohydrate inherent chair conformation much.Instead,the gem-difluoro-carbasugar glycosides seem more stable due to their lower free energy?G.Based on the surflex-docking results towards CD1d,some of the gem-difluoro-carbasugar derivatives are designed and expected to show stronger binding activities than the immune stimulant?-GalCer.In Chapter two,the synthetic method of gem-difluoro-carbasugar was established.Xylose and 3,3-difluoro-3-bromopropene were used as the raw materials to synthesize gem-difluoro-carbaglucose and carbasugar galactose through a series of reactions of Barbier reaction,olefin metathesis,and Prins 1,3-dihydroxylation.Our research demonstrated that difluoro-cyclohexene structures are not good substrates for Prins dihydroxylation and olefin epoxidation due to the passivation effect of allyl difluoride.Subsequently,the gem-difluoro-carbasugars were effectively prepared from normal sugars through key reactions of Ferrier rearrangement,carbonyl?-Hydroxy-methylation and carbonyl difluorination.In Chapter three,the above established method is firstly used to synthesize gem-difluoro-carba-arabinose.The related ceramide side chains with different chain lengths are prepared from phytosphingosine and D-mannose.Based on these two building blocks,a gem-difluoro-carba-arabinose-containing?-GalCer analog was synthesized,for the first time,via cyclic sulfonation of 1-OH and 2-NH₂,Staudinger reaction,and ether-formation between gem-difluoro-carbasugar and ceramide side chain.