Synthesis of Carbohydrate Molecules of Biological Importance

Abstract

Carbohydrates represent one of the most privileged classes of naturally occurring compounds due to functional and sterochemical wealth associated with them. Besides their role as biological scaffolds and energy reservoirs in the living cell, they play vital roles in physiological processes such as cellular adhesion, cell-cell recognition, signal transduction, fertilization, protein folding, neurobiology, xenotransplantation, target recognition in the immune response etc. For chemists they are interesting as both target molecules and sources of enantiopure synthons (chiron approach) for the synthesis of natural products and drugs. In recent years carbohydrates have been the focus of growing attention among medicinal and synthetic chemists as carbohydrate based therapeutics are associated with low toxicity and immunogenicity compared to their peptide counterparts. So development of new methods to synthesize diverse carbohydrate derivatives is of great demand. For the present study we have identified two monosaccharide derivates namely 3,4,6-tri-O-acetyl-D-glucal and galactal, easily preparable in three steps on multi gram scale starting from D-glucose and D-galactose respectively, as the lead molecules. The work embodied in this thesis is an attempt to exploit the huge potential lying in these monosaccharide derivatives. The thesis comprises of six chapters distributed into two parts namely Part A and Part B. Part A of the thesis consists of four chapters which deal with the development of novel carbohydrate synthons and their utilization in the synthesis of biologically important molecules. In order to provide insight, the first chapter of the dissertation presents an historical overview of the synthesis of δ-hydroxy-α,β-unsaturated aldehdyes commonly called perlin aldehdyes, obtainable by simple mercuric-ion assisted acid hydrolysis of glycals, and their utilization for the synthesis of various biologically important classes of compounds. The start of chapter 2 presents a brief introduction on synthesis and mechanistic aspects of Sharpless asymmetric epoxidation reaction, since the forthcoming sections, namely 2A, 2B and 2C, of this chapter include the synthetic applications of the 2,3-epoxy alcohols derived from their respective glycals. The next two chapters, chapter 3 and 4 describes the detailed account of the steroselective synthesis of pachastrissamine (jaspine B), a cytotoxic anhydrosphingosine and oxybiotin, an oxygen analog of vitamin-H biotin utilizing novel synthons developed in our laboratory. Part B of the thesis consists of two chapters. Chapter 5 describes a brief review on recent trends in drug discovery of tuberculosis while the other, chapter 6 describes the synthesis and biological studies of enantiopure tetrahydrofuran 1,2,3-triazoles, prepared from our reported THF domains, involving “click” chemistry. Each chapter is followed by the bibliography, experimental data and selected spectra supporting the information presented in the chapter. The compound numbers, figure numbers, scheme numbers and bibliography numbers are separate for each data. The list of abbreviations used and the general remarks are presented at the beginning of the dissertation for referring.