Synthesis of a 28-mer oligosaccharide core of Mycobacterial lipoarabinomannan (LAM) requires only two n-pentenyl orthoester progenitors

Abstract

Regioselective glycosidation of acceptor polyols greatly reduces the number of orthogonal protecting groups that are normally required for conventional syntheses of highly branched oligosaccharides. The MATCH between a donor and one of the many-OHs is the basis of a simple, ready synthesis of the 28-mer oligosaccharide described in this manuscript. The strategy relies heavily upon the unique interplay between n-pentenyl orthoesters (NPOEs), n-pentenyl glycosides, ytterbium triflate, and N-iodosuccinimide which allows exquisite, high-yielding regio- and chemoselective glycosylations. The NPOEs, effective as mannose or arabinose donors, are the sole sources of all saccharide components of the lipoarabinomannan oligosaccharide. Once considerable systematic research had been invested, the 12-mer mannan, 92, and 16-mer capped arabinan, 91, domains can be rapidly assembled in 300 mg and 1 g quantities, respectively, using conventional laboratory equipment. The 28-mer, 93 (MW = 11122.54) is, as far as we are aware of, the largest hetero-oligosaccharide that has been synthesized.