Synthesis of Chlamydia lipopolysaccharide haptens via α-specific 3-iodo-Kdo fluoride glycosyl donors

• Published in: Chemistry : a European journal 2014-10, Vol.21 (1), p.305-313
• Main Authors: Pokorny, Barbara, Kosma, Paul
• Format: Article
• Language: English
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201405424

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 route to generate 3-iodo Kdo fluoride donors from Kdo glycal esters, which enable efficient α-specific glycosylations and significantly suppress the elimination side reaction. The potency of these donors is demonstrated in a straightforward, six-step access to a branched Chlamydia-related Kdo-trisaccharide ligand without the need of 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.