Synthesis of bacterial oligosaccharides : developments in the construction of cis-glycosidic linkages

Abstract

This thesis describes the development and application of different methods for the construction of 1,2-cis glycosidic bonds, which remains one of the most challenging aspects in synthetic carbohydrate chemistry. In Chapter 2 a synthesis of an orthogonally protected 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose (AAT) building block starting from D-glucosamine is outlined. Chapter 3 describes a modular approach towards the synthesis of all possible trimer repeating units of the type 1 capsular polysaccharide of Streptococcus pneumonia, Sp1. The difficulty associated with the efficient stereoselective introduction of _-galacturonic acid bonds was overcome by employing galacturonic acid-[3,6]-lactone building blocks. Chapter 4 describes a study of the reactivity and stereoselectivity of a galacturonic acid-3,6-lactone thioglycosyl donor in comparison with protected galacturonic acid and galactose donors using a series of competition experiments and condensation reactions with different thiophilic activator systems. Chapter 5a describes the application of a panel of C-6 thioether mannosyl donors, a C-6-selenoether donor and a C-6-iodide N-phenyltrifluoroacetimidate mannosyl donor in a series of condensation reactions. The applicability of one of these 1,2-cis-mannosylating agents is the subject of Chapter 5b. Upon condensation of 6-thio-6-deoxy-mannosyl donors reductive removal of the 6-thio functionality provides 1,2-cis rhamnosides. Following this methodology a backbone tetrasaccharide containing alternating _- and _-D-rhamnosides was synthesized.