Synthesis of a Phosphorylated Disaccharide Fragment of the O-Specific Polysaccharide of Vibrio cholerae O139, Functionalized for Conjugation

• Published in: Helvetica chimica acta Vol. 89; no. 2; pp. 320 - 332
• Main Authors: Ruttens, Bart, Kováč, Pavol
• Format: Journal Article
• Language: English
• Published: Zürich WILEY-VCH Verlag 01-02-2006; WILEY‐VCH Verlag
• Subjects: Cyclic phosphates; Glycoconjugates; Glycosylation; Phosphates; Vaccines; Vibrio cholerae
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.200690036

The title disaccharide, 2‐{2‐{2‐[(2‐ethoxy‐3,4‐dioxocyclobut‐1‐en‐1‐yl)amino]ethoxy}ethoxy}ethyl 2‐O‐(3,6‐dideoxy‐α‐L‐xylo‐hexopyranosyl)‐β‐d‐galactopyranoside cyclic 4,6‐(potassium phosphate) (2), was synthesized from the two isomeric linker‐equipped galactose acceptors 9 and 10, obtained by phosphorylation of 2‐[2‐(2‐azidoethoxy)ethoxy]ethyl 3‐O‐benzyl‐β‐d‐galactopyranoside (8), which were glycosylated with ethyl 2,4‐di‐O‐benzyl‐3,6‐dideoxy‐1‐thio‐β‐l‐xylo‐hexopyranoside (12; Scheme). Mainly the fully protected α‐(1 → 2)‐linked products 13α and 14α were formed. Catalytic hydrogenolysis/hydrogenation effected global deprotection, thereby removing the chirality at the P‐atom, and simultaneously converted the azido group in the linker to an amino group (→ 15). Final treatment with diethyl squarate (= 3,4‐diethoxycyclobut‐3‐ene‐1,2‐dione) gave target compound 2, amenable for conjugation to proteins.