The Lipoarabinomannan Glycolipid ofMycobacterium tuberculosis : Progress in Total Synthesis via n-Pentenyl Orthoesters

The lipoarabinomannan (LAM) cell surface glycolipid of Mycobacterium tuberculosis anchors a complex, highly branched glycan comprising arabinofuranan, mannan, and mannose-capped arabinan domains. This multifaceted architecture mirrors a multifaceted biological profile that implicates LAM in a wide range of health disorders, tubercular and non-tubercular, in addition to serving its principal role of protecting the bacterium against assault by diagnostic and therapeutic agents. Syntheses of the various domains of LAM have been undertaken to assist in structure-activity analysis. The approach revives Paulsen's concept of donor/acceptor MATCH as a prime requirement in oligosaccharide assembly. A major advantage of the strategy is that if MATCH can be applied to effect monoglycosylation of a polyol, the most labor-intensive synthetic tasks can be avoided, since misMATCHed hydroxyls need not be protected - and subsequently deprotected. n-Pentenyl orthoesters (NPOEs) are pivotal for the MATCH approach, and extending the method to arabinofuranosyl donors presents a new tool for furanoside syntheses. Notably, the reducing end of the arabinofuranan oligomers can be liberated by oxidative hydrolysis, thereby avoiding the perils of the acid-catalysed alternative.