Total Synthesis of the Trisaccharide Antigen of the Campylobacter jejuni RM1221 Capsular Polysaccharide via de Novo Synthesis of the 6‑Deoxy‑d-manno-heptose Building Blocks

• Published in: Journal of organic chemistry 2019-03, Vol.84 (5), p.2393-2403
• Main Authors: Wang, Xiaoman, Chen, Yan, Wang, Junchang, Yang, You
• Format: Article
• Language: English
• Subjects: Antigens, Bacterial - chemistry; Antigens, Bacterial - immunology; Bacterial Capsules - chemistry; Bacterial Capsules - immunology; Campylobacter jejuni - immunology; Glycosylation; Heptoses - chemical synthesis; Polysaccharides, Bacterial - chemistry; Polysaccharides, Bacterial - immunology; Trisaccharides - chemical synthesis; Trisaccharides - immunology
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.8b02394

A de novo approach utilizing the d-proline-catalyzed and LDA-promoted aldol reactions as key steps for the preparation of differentiated-protected 6-deoxy-d-manno-heptose building blocks was developed. PPh3AuBAr4 F-catalyzed glycosylation with the 6-deoxy-d-manno-heptosyl o-hexynylbenzoate as donor was demonstrated as a direct and practical method for the stereoselective synthesis of the β-linked 6-deoxy-d-manno-heptoside as the major product. Coupling of the 6-deoxy-α-d-manno-heptosyl H-phosphonate with the 3-hydroxyl disaccharide acceptor based on H-phosphonate chemistry was described for the construction of the trisaccharide skeleton with the acid-labile phosphodiester linkage. Finally, first total synthesis of the unique trisaccharide antigen of the capsular polysaccharide of Campylobacter jejuni RM1221 that belongs to HS:53 serotype complex was accomplished for further evaluation as vaccine candidate against C. jejuni RM1221 infection.