Synthesis Of Azasugar Derivatives

Azasugars in which the ring oxygen has been replaced by nitrogen are now believed to be widespread in plants and microorganisms, and they also can be called imionsugars. Azasugars and their derivatives have exhibited remarkable biological activity to inhibit glycoside-processing enzymes, with resulting potential chemotherapeutic applications against diabetes, cancer, and viral infections including AIDS. Recently, because of the important biological activity and excellent foreground on pharmaceutical application, great attention has been attracted to the synthesis of their new derivatives and analogues.In this thesis, the recent methods of synthesizing azasugars were firstly reviewed. On the basis of the comparison of the methods, a suitable synthetic way was selected and a partially protected derivative of 5-membered azasugar derivative 11 was synthesized via the key intermediate of norbonyl like bicyclic acetal using D-glucose as the starting materials. In this synthetic process, only two times of purification by chromagraphic column were performed with yield upto 30.1% in all over the 12 steps, providing a very convenient and practical method for synthesizing azasugar derivatives. Furthermore, in order to explore the synthesis of new disaccharide analogues containing azasugar moiety, a series of amino azasugar derivatives 13 were syntheszed by reductive amination using 11 and primary amines. The structures of the synthesized new compounds were characterized based on the analyses of ¹HNMR, ¹³CNMR and MS spectra.In addition, the synthesis of six-member gluconolactam was approached by ammonolysis, oxidation and then intramolecular reductive amination from the corresponding glucolactone.