Synthesis of chlamydia lipopolysaccharide haptens through the use of α-specific 3-iodo-Kdo fluoride glycosyl donors

Abstract

A scalable approach towards high-yielding and (stereo)selective glycosyl donors of the 2-ulosonic acid Kdo (3-deoxy-D-manno-oct-2-ulosonic acid) is a fundamental requirement for the development of vaccines against Gram-negative bacteria. Herein, we disclose a short synthetic route to 3-iodo Kdo fluoride donors from Kdo glycal esters that enable efficient α-specific glycosylations and significantly suppress the elimination side reaction. The potency of these donors is demonstrated in a straightforward, six-step synthesis of a branched Chlamydia-related Kdo-trisaccharide ligand without the need for protecting groups at the Kdo glycosyl acceptor. The approach was further extended to include sequential iteration of the basic concept to produce the linear Chlamydia-specific α-Kdo-(2→8)-α-Kdo-(2→4)-α-Kdo trisaccharide in a good overall yield.

Keywords: carbohydrates; diastereoselectivity; glycosylation; immunochemistry; oligosaccharides.