RECENT DEVELOPMENTS IN TECHNOLOGY FOR GLYCOSYLATION WITH SIALIC ACID

Abstract

Sialic acids are a class of nine-carbon monosaccharides found at the termini of oligosaccharides in many mammalian cellular systems [1]. This class is represented by the prototypical congener N-acetylneuraminic acid (NeuAc, 1, Scheme 1). These unique sugars are ubiquitous, and they are present as components of both glycolipids and glycoproteins. Some examples of sialic acid containing oligosaccharides are shown in Scheme 2. Sialic acids are found in variety of glycosidic linkages, some more common of which are α-2,3or α-2,6-linkages to galactose residues. Additionally, they frequently exist as α-2,8-linked oligomers or polymers. The lack of efficient technology to accomplish glycosylations with sialic acid is one of the long-standing deficiencies in carbohydrate chemistry [2]. Owing to the central role of sialic acids in carbohydrate recognition events, the development of high-yielding and operable methods to synthesize sialic acid glycosides has been the subject of considerable research. The development of such methods allows the construction of complex sialic acid containing glycoconjugates for the investigation of their roles in biochemical and cellular processes. Most classical methods for synthesizing sialic acid glycosides are based on the reaction of an activated sialic acid such as 2 with an oligosaccharide glycosyl acceptor bearing a hydroxyl group nucleophile (Scheme 3) [2]. The leaving group is typically a halogen, such as a chloride or bromide, and the activator is typically a heavy metal salt [3,4]. A regioselective union of the two reacting partners of course relies on appropriate protecting group patterns for both the glycosyl donor and acceptor components. Many of the early methods are generally plagued with side reactions, low yields, and poor stereoselectivity. There are several reasons for