Controlled ring-opening polymerization of 1,2,6-tricyclic orthoesters of mannose toward size–controlled α-d-mannopyranan

Abstract

Lipomannan (LM), one of the major components of glycans found on the cell wall of Mycobacterium tuberculosis, plays a critical role in interacting with host cells and moderating immune response. The backbone of LM is composed of α(1-6) mannopyranan, consisting of approximately 10-15 repeating mannose residues. Rapid synthesis of α(1-6) mannopyranan has been accomplished by ring-opening polymerization using 3,4-O-benzyl-β-dmannopyranose 1,2,6-orthobenzoate (1) as a starting monomer. Here, we report the progress on attempts to control the size of α(1-6) mannopyranan polymer products. It is possible to prepare α-d-mannopyranan polymer products in different sizes by varying the monomer concentration.

Synthesis and Immunological Studies of the Lipomannan Backbone Glycans Found on the Surface of Mycobacterium tuberculosis

“…Certain bacterial polysaccharides are extremely difficult to produce in pure identity through bacterial cell cultures and therefore are not available in sufficient scales for thorough research investigations and commercial purposes. The macromolecular nature and the structural complexity of LM have been the primary obstacles for elucidating the structural-activity relationship of LM through a traditional stepwise synthetic approach. − It is also difficult to use genetic/enzymatic engineering to produce the bacterial polysaccharides because of the limited availability in specific enzymes to synthesize diverse polysaccharides structures, and the post-translational nature of glycan biosynthesis. , Synthetic efforts aimed at producing large polysaccharides such as automate solid phase or one pot solution phase strategies have been made, however, these strategies are limited to small scales. − Since the development of rapid and practical synthesis is essential to reveal the vital components and configurations for LM’s biological activities, our team has been committed to the development of a rapid synthetic approach for the LM glycan backbone. − The LM glycan backbone−α(1–6)­mannans had not been available before in pure identity, and thus the immunological properties of this exact LM component has never been experimentally revealed. The current study demonstrates a rapid synthesis of the polysaccharide backbone found on the Mtb surface, already equipped with a linker.…”