SYNTHESIS OF GLUCOSAMINE DERIVATIVES CONTAINING HEPARAN SULFATE FRAGMENTS

Abstract

ABSTRACT Synthesis of Glucosamine Derivatives Containing Heparan Sulfate Fragments Heparan sulfate (HS) and heparin belong to two prominent families of glycosaminoglycans (GAGs) which are capable of binding hundreds of protein ligands and playing a key role in a variety of biological processes including anticoagulant, viral infection, amyloid diseases, and angiogenesis. Their diverse spectrum of biological activities has various therapeutic applications. As a result, GAGs and their family have sparked significant interest in the discovery of novel medications and illness therapy. This project is mainly focused on synthesis of a glucosamine derivative which acts as an acceptor. The used of various protecting groups is believed to increase the potential of binding with protein as well as a good approach once the glucosamine derivatives undergo glycosylation reaction to form HS disaccharide building blocks. A number of synthetic methods was used in attempt to synthesise GlcN acceptors using several protecting groups such as acetyl, thioglycoside, benzylidene acetals, benzoyl and benzyl. The five GlcN acceptors were successfully synthesised which can be potentially developed further to another new end modifications or through glycosylation reactions to produce HS disaccharides. FTIR, mass spectrometry, and NMR were used to characterise the end products of each pathway. Despite finding that glycosylation reactions were not completed, this investigation produced useful knowledge regarding the reactivity of GAG fragments and modification of some protocols for purification.

Date of Award	31 Dec 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	John Gardiner (Supervisor)