Polymerization of mannosyl tricyclic orthoesters for the synthesis of alpha(1-6) mannopyranan-the backbone of lipomannan.

Tuberculosis (TB) remains a major health problem worldwide. Understanding the interactions between the surface components of Mycobacterium tuberculosis (Mtb), the main causative agent of TB, with host immune response will be critical for developments of effective treatments and prevention of TB. Chemically defined mimics of the bacterial envelope components serve as important tools for biological studies of the bacterial interactions with mammalian hosts. We report here a rapid synthetic approach utilizing mannosyl tricyclic orthoesters as monomers for regio- and stereo-controlled polymerizations to generate alpha(1-6) mannopyranan-the backbone of lipomannan. The polymerizations generated multiple glycosidic bonds in a single chemical transformation in regio- and stereo-selective manners. TMSOTf is the optimum catalyst to promote the selective and high yielding polymerization when compared with other Lewis acids. In addition, the monomers 3,4-O-benzyl-beta-d-mannopyranose 1,2,6-orthobenzoate (1) and 3,4-O-benzyl-beta-d-mannopyranose 1,2,6-orthopivalate (2) can be synthesized in multiple-gram scale and in a rapid fashion. Characterizations by GPC and NMR indicate the identity of alpha(1-6) mannopyranan with DPn (degree of polymerization)=20.