Total Synthesis of the Morganella Morganii Zwitterionic Polysaccharide Repeating Unit

Abstract

Zwitterionic polysaccharides (ZPS) activate T-cell-dependent immune responses by major histocompatibility complex class II presentation. Herein, we detail a review of the field of ZPSs and report the first synthesis of a Morganella morganii ZPS (MM-ZPS) repeating unit as an enabling tool in the synthesis of novel ZPS materials. The repeating unit incorporates a 1,2-cis--glycosidic bond; the problematic 1,2-trans-galactosidic bond, Gal-β-(1→3)-GalNAc; and phosphoglycerol and phosphocholine residues which have not been previously observed together as functional groups on the same oligosaccharide. Three unique synthetic campaigns to achieve synthesis of the MM-ZPS are examined within the text; highlighting trials and tribulations of each. The successful third generation approach leverages a first in class glycosylation of a phosphoglycerol functionalized acceptor. To install the phosphocholine unit, a highly effective phosphocholine donor was synthesized.