ABSTRACT
Complex carbohydrates are components of a broad range of molecular structures in nature. They are frequently found as components of cell surface glycoproteins and glycolipids, playing an important role in cellular communication processes [l] and as points of attachment for antibodies and other proteins. The major classes of cell surface glycolipids include the glycosphingolipids (GSLs) and glycoglycerolipids. Particularly significant are gangliosides [2], or sialic acid-containing glycosphingolipids, which are especially abundant on neural cell surfaces [3]. These compounds play a role in the differentiation of cell types and in the regulation of cell growth. Oligosaccharides and polysaccharides also serve as receptor sites for bacteria [4] and viral particles [5]. The saccharide moieties of glycoproteins are also involved in modulating protein folding and in the sorting and trafficking of proteins to appropriate cellular sites [l]. Carbohydrates often occur in minute quantities and are difficult to isolate in a pure form, characterize, and in particular, synthesize in amounts sufficient for therapeutic study and biological evaluation. The pace of development of carbohydrate-derived therapeuticals, therefore, has been slower than with other classes of biomaterials (i.e., peptides or nucleic acids) that are more easily accessible by automatic solid-phase synthesis. One of the major difficulties in oligosaccharide synthesis is the task of coupling building blocks in a stereoselective manner. Particularly difficult are the synthesis of f3-mannosides, for which some elegant solutions have only recently appeared [6, 7], and the synthesis of glycosides of sialic acids [8]. A second difficulty encountered in oligosaccharide synthesis originates from the polyfunctionality of these compounds, which necessitates the use of elaborate protective group chemistry if complex carbohydrates are to be synthesized through conventional methods. Although considerable progress has been made recently toward the development of more sophisticated synthetic methods directed at the synthesis of glycoconjugates (see Chap. 9), the chemical synthesis of biologically interesting complex carbohydrates on a scale larger than 1 mmol still appears to be a problem not yet solved. Alternatively, the enzymatic approach avoids the problems encountered in the chemical synthesis and is increasingly considered to be useful for the practical synthesis of certain complex oligosaccharides and glycoconjugates, albeit some drawbacks are also encountered.
