Total Synthesis of the Congested, Bisphosphorylated <i>Morganella morganii</i> Zwitterionic Trisaccharide Repeating Unit

Abstract

Zwitterionic polysaccharides (ZPSs) activate T-cell-dependent immune responses by major histocompatibility complex class II presentation. Herein, we report the first synthesis of a <i>Morganella morganii</i> ZPS repeating unit as an enabling tool in the synthesis of novel ZPS materials. The repeating unit incorporates a 1,2-<i>cis</i>-α-glycosidic bond; the problematic 1,2-<i>trans-</i>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. 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.