Total Synthesis of the Tumor-Associated Carbohydrate Antigen Lewis A Lewis X Hexasaccharide and Selected Fragments

Abstract

Carbohydrates constitute the most abundant class of natural products in the living world and they play various roles. They are notably involved in cell-cell interactions and immune reactions. It has been observed that tumor cells express, on their surface, unusual oligosaccharides named Tumor-Associated Carbohydrate Antigen (TACA). One TACA of interest to our research group is the Lewis A Lewis X hexasaccharide that is displayed on the surface of squamous lung carcinoma cells. Since carbohydrates are involved in immune reactions and can be recognized by antibodies, it becomes possible to design a carbohydrate-based vaccine against these tumor cells. This thesis describes the total synthesis of the TACA Lewis A Lewis X hexasaccharide and the preparation of two fragments: one tetra- and one pentasaccharide. These molecules were prepared as hexyl and aminohexylglycosides. In addition, the hexasaccharide was synthesized as a disulfide. This diversity of these synthons will allow conjugation to a protein, analysis by nuclear magnetic resonance techniques, and immobilization on gold of the antigen. Without doubt, this work is a significant contribution to the development of an anti cancer vaccine as it constitutes the first stage of the process.