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

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 13 α and 14 α 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.