Automated Parallel Synthesis of a Protected Oligosaccharide Library Based upon the Structure of Dimeric Lewis X by One-Pot Sequential Glycosylation

Abstract

A u t o m a t e d P a r a l l e l S y n t h e s i s o f a P r o t e c t e d O l i g o s a c c h a r i d e L i b r a r yAbstract: An efficient synthesis of a protected dimeric Lewis X epitope by two sequential one-pot glycosylations is described. Combinatorial synthesis of the dimeric Lewis X epitope derivatives by the one-pot glycosylation was accomplished utilizing an automated synthesizer to provide 12-protected oligosaccharides.Oligosaccharides on cell surface play important roles in many biological processes. 3 Most biologically active oligosaccharides are rare, and are difficult to purify. Additionally, their structural diversity based upon stereo-and regioisomers makes it difficult to determine their structure in comparison with that of oligopeptides and oligonucleotides. Therefore, the chemical synthesis of such oligosaccharides would strongly assist one in the elucidation of their structure-activity relationships. Recent developments of the chemical synthesis of oligosaccharide involving automated solid-phase synthesis, allows the high speed synthesis of a single target oligosaccharide. 4,5 Furthermore, combinatorial chemistry enables one to synthesize oligosaccharide libraries containing tri-or tetrasaccharides. 6,7,8d However, preparation of biologically active and complex natural product-based oligosaccharide libraries is still difficult to accomplish.One-pot glycosylation, involving sequential activation of glycosyl donors in a single vessel, is effective not only for the high speed synthesis of a single target oligosaccharide, but also for the parallel synthesis of oligosaccharide libraries. 7c,8,9 We have investigated the one-pot glycosylation based on the chemoselective activation of glycosyl donors attached with different leaving groups with appropriate activators, 9 and have already reported a one-pot sixstep synthesis of a di-branched heptasaccharide composed of a b(1,6) linked pentasaccharide backbone using seven independent building blocks. 9f If the requisite manipulations in the one-pot glycosylation are adaptable to an automated synthesizer, it would be an attractive way to synthesize structurally complex oligosaccharides. Scheme 1 Strategy for the one-pot synthesis of dimeric Lewis X derivative 1.