Design And Synthesis Of Difluoromethylenated Thiosugar

Thioosugars, as potential glycosidase inhibitors, have attracted increasing attention from synthetic chemists and biochemists. It is well known that introduction of fluorine atom(s) or fluorine-containing group into an organic compound can bring remarkable changes in the physical, chemical and biological properties. However, few fluorinated thiosugars have been investigated. In view of above mentioned facts, we designed a series of gem-difluoromethylenated thiosugar and investigated their synthesis. The dissertation is divided into two parts.Part Ⅰ:Design and synthesis of difluorinated thio-deoxythionojirimycin (DNJ). The precursors of four stereoisomers of difluorinated thio-DNJ were efficiently synthesized from (R)-glyceraldehyde acetonide and3-bromo-3,3-difluoropropene via a series of functional group transformations, protection/deprotection, and Na2S-9H2O mediated ring closure reaction.Part II:Design and synthesis of difluorinated analogues of ThioDapagliflozin. Two synthetic routes to difluorinated ThioDapagliflozin were investigated. The key sulfur-containing intermediate35were prepared from (R)-glyceraldehyde acetonide and3-bromo-3,3-difluoropropene in17steps.