New Synthetic Methodology for Regio- and Stereoselective Synthesis of Oligosaccharides via Sugar Ortho Ester Intermediates.

Great effort has been devoted to the development of new strategies for glycosidic coupling owing to the growing importance of synthetic oligosaccharides in glycobiology.1 In the past decades, methods for construction of glycosidic linkages have progressed considerably.2 However, compared to the synthesis of oligopeptides and oligonucleotides, the synthesis of oligosaccharides is still laborious work. The use of unprotected or partially protected sugars in glycosidic coupling is of particular interest since synthetic routes can be substantially simplified. In addition, chemistry on unprotected sugars represents a great challenge, as there are only tiny differences in coupling sugar hydroxyl groups, particularly secondary hydroxyl groups. Formation of sugar-sugar ortho esters in glycosylation is well-known, and these ortho esters are obtained in variable yields,3a-i sometimes as byproducts,3j but there have been no reports dealing with the preparation of ortho esters using unprotected or partially protected glycosides as the glycosyl acceptors. In addition, TMSOTf-promoted rearrangement4 has only been used to treat fully protected ortho esters formed from reaction with either the primary4a,b hydroxyl group of a sugar acceptor or a simple aglycon alcohol.4c We now report a new methodology for highly regioand stereoselective synthesis of oligosaccharides. That is, (1) the preparation of sugar-sugar ortho esters by coupling acetobromosugars with unprotected alkyl glycosides or partially protected sugar acceptors in high yields and excellent selectivity and (2) the rearrangement of either partially protected or fully protected ortho esters of diverse structure by the catalytic use of TMSOTf.