Synthesis Of Novel Indolizidine Derivatives With An Amino Group

Polyhydroxylated indolizidines strictly speaking, belong to azasugars, are bicyclic alkaloids where the azapyranose ring is fused to a pyrrolidine ring via an N-bridge. The well know swainsonine and castanospermine are naturally occurring and typical bicyclic azasugar analoges, and exhibited effective glycosidase inhibition and potential therapeutic applications as antidiabetic, antiviral, anticancer and antimetastatic immunoregulating agents. Such promising applications and the interesting bicyclic structure of polyhydroxlated indolizidines have attracted great interests to approach the convenient and efficient synthetic methods and to build up the diversity of the compounds for improving their biological activity and selectivity, and diminishing toxicity.In this thesis, on the basis of reviewing the recent progress of the synthesis of Polyhydroxylated indolizidines, the novel amino polyhydroxylated indolizidines was designed and synthesized. Thus, a partially protected 5-membered azasugar nitrone 13 was synthesized via the key intermediate of norbonyl like bicyclic acetal using D-glucose as the starting materials. The key steps of the strategy involved an effectively microwave assisted 1,3-dipolar cycloaddition of azasugar nitrone and methacrylate for installing a potential amino group and an ester group with a extended chain, and a structurally controlled intramolecular cyclo-amidation for constructing the indolizidine ring system via a key tricyclic indolizinone-containing intermediate, with total yeild of 11.1-12.5%. The structures of all of the synthetic intermediates and products have been characterized on the basis of the analyses of X-ray,1H NMR, 13C NMR, H-HCOSY, HSQC, NOESY and FAB-MS spectra.