Chemical approaches for the study of the mycobacterial glycolipids phosphatidylinositol mannosides, lipomannan and lipoarabinomannan

The mannose-rich mycobacterial glycophospholipids phosphatidylinositol mannosides (PIMs), lipomannan (LM), and lipoarabinomannan (LAM) are important constituents of the mycobacterial cell wall and are critical mediators of host-pathogen interactions. Since the earliest reports of their existence almost 80 years ago, intensive efforts have now resulted in an almost complete description of their molecular structures. In parallel, based on studies over the last 10 years, their biosynthesis is now reasonably well understood. Owing to the structural complexity of these glycophospholipids, chemically synthesized fragments have been essential for dissecting their biosynthesis and biological functions. This review provides an overview of the synthesis of fragments of the PIMs, LM and LAM, and approaches to the total synthesis of PIMs and analogues. Also covered are uses of synthetic fragments, authentic structures and analogues as biochemical reagents and immunomodulators.