Synthesis of Phosphatidylinositol Mannosides

The cell envelope of mycobacterial species, which include the deadly Mycobacterium tuberculosis, carries unique glycan structures that are crucial for infection and bacterial survival. Notable among these glycans are the structurally-related phosphatidylinositol mannosides (PIMs), lipomannan, and lipoarabinomannan. The immunoactivities of these structures attracted considerable attention from synthetic chemists and biologists alike, who are keen on evaluating vaccine or adjuvant properties. Moreover, PIMs are interesting synthetic targets because of the regio- and stereoselective considerations in generating the inositol and mannosyl cores. In this paper, we summarize the recent efforts in the chemical synthesis of PIMs as well as their analogues. Particular emphasis is given on the challenges associated with the preparation of the chiral myo-inositol derivatives, the regioselective installation of mannosyl residues, and phosphatidylation strategies. The results of the bioevaluation of selected compounds are also briefly described.