The Synthesis Of Conformationally-restricted Polyhydroxylated Alkaloid

Polyhydroxylated alkaloids as an important class of glycosidase inhibitor display a range of important biological activities and have potentials as chemotherapeutic agents. The main categories of structure include hydroxylated piperidines, pyrrolidines, indolizidines, pyrrolizidines and nontropanes. These sugar mimics inhibit glycosidases because of a structureal resemblance to the sugar moiety of the natural substrate. Due to the stereoelectronic factors playing a key role in the pathway through which a glycoside is enzymatically hydrolyzed, conformationally-restricted polyhydroxylated alkaloids are valuable substrates to study the SAR.In this thesis, a novel kind of polyhydroxylated alkaloid possessing a bridged bicyclic structure was synthesized as the conformationally-restricted polyhydroxylated alkaloids. These novel bicyclic compounds are also versatile intermediates toward the preparation of libraries of aryl-substituted polyhydroxylated pyrrolidines.Thus, using D-(+)-glucose as the starting material, we undergo 10 steps to obtain two novel bridged bicyclic compounds. Key steps in the synthesis included introducing aryl group by Grignard reaction, transforming hydroxyl group to azide group with Mitsunobu reaction and an intramolecular cyclization are key steps.