Synthesis and Antifungal Evaluation of Spirostane Saponins

Methods for the preparation of novel antifungal saponins have been investigated in order to further explore their medicinal utility and provide the opportunity to synthesize their derivatives. Through this work, several partially protected stereoisomers of Cholestane, Androstane and Spirostane have been prepared which could be used for the synthesis of various saponin derivatives in order to discover novel saponin based antifungal agent. Various mono and disaccharide derivatives of these steroids have been synthesized and evaluated for their antifungal activity against four pathogenic fungal strains. Among the various derivatives maltose derivatives were found to have the best antifungal activity. However there is a need for more extensive SAR studies to discover compounds with better potency. Additionally, the branched oligosaccharide synthesis was explored in two parts. First, these results demonstrated that the central 2,3-branched portion can be synthesized efficiently from a partially protected glucopyranosyl acceptor since the C-2 and C-3 alcohols differ in their reactivity in glycosylation reactions. Second, a tagged sugar based strategy for synthesis of branched oliogosaccharides was developed, and found to be effective for general synthesis of branched oligosaccharides. Microwave assisted synthesis of cyclic imides have been explored this was a key precursor for the synthesis of our tag molecules which were required for synthesis of branched oligosachharides. A comparison of microwave versus conventional methods for synthesis of cyclic imides has been studied. The synthesis of tagged sugars and their selective deprotection to remove tag molecules were successfully explored in order to have proof of concept for its applicability towards synthesis of branched oligosaccharides. Benzylic mono and dibromination was achieved in very high yields using microwave conditions using environmentally friendly solvent in order to avoid use of carcinogenic carbon tetrachloride as solvent for this type of reactions. In addition reaction time was reduced to 30 minutes to 3 hours compared to convention methods, which needed more than 15 hours for the benzylic bromination reaction.