Synthesis of Selectively Protected Chitobiose and Chitotriose Derivatives from one Precursor. Versatile Building Blocks for Oligosaccharide Synthesis

Abstract

The inner core region of cell surface N-glycoproteins consists of a chitobiose substructure², containing β-(1,4)-linked disaccharides of glucosamine. Such carbohydrate structures are also found as repeating units of the bacterial cell wall peptidoglycan³ and in novel tetra- and pentasaccharide plant hormones, which are nodulation factors on legume roots.⁴ Since the first synthesis of a chitobiose derivative in 1966 by Paulsen,⁵ approaches to these compounds have relied mainly on the oxazoline method.⁶ The coupling reactions of aminosugar chlorides,⁷ bromides,⁸ acetates⁹ and trichloroacetimidates¹⁰ to suitable glycosyl acceptors have also been described. Most of these syntheses¹¹ require two completely different coupling partners; only in very few examples could the glycosyl donor and acceptor be obtained from the same starting material.¹² During our investigations into the stereocontrolled synthesis of glucosamine oligosaccharides, we required an economical synthetic route to protected derivatives of chitotriose. For the purpose of easy oligomerization, the anomeric protecting group of every building block had to be exchangeable selectively with the activating group for the next glycosylation. In this paper, we report an efficient approach to chitobiose and chitotriose from a single precursor. Furthermore, the hydroxyl groups at C-1, C-3, C-4, C-6 of these oligosaccharides are differentially protected. This protecting group scenario allows a specific access to any of these functionalities by regioselective deblocking. The N-phthalimide group was chosen out of several possible amino protecting groups to ensure β-selectivity and simultaneous activation in the coupling.¹³