Executive Summary : | Cancer and viral diseases are major causes of human mortality, with nucleosides drugs being the primary treatment for various viral diseases. However, the emergence of new viral strains, drug resistance, and toxicity due to prolonged use of existing drugs make the search for more efficacious new drugs inevitable. High throughput screening in drug discovery research has led to a demand for new molecules with structural, stereochemical diversity, and privileged bioactivity in stereo-chemically pure form. This project proposes synthesizing a series of nucleosides with good structural and stereochemical diversity in stereoisomerically pure form, starting from an inexpensive natural chiral pool of D-glucose. The simple reaction sequence involves generation of suitable alkene-aldehydes, intramolecular nitrone cycloaddition reaction, hydrogenolysis of isoxazolidines, and construction of diverse nucleoside bases on the free amines of these amino alcohols. In vitro bioassays will be conducted against various cancer cell lines and viral strains, with compounds with intriguing in vitro bioactivity selected for evaluation of in vivo efficacy and experimental and computational exploration of the mechanism of inhibition. |