First Synthesis of A Branched Pentasaccharide Representative of The Repeating Unit of The Shigella Flexneri Serotype 5A O-Antigen

ABSTRACT

Based on the use of a 2-deoxy-2-trichloroacetamido-D-glucopyranosyl donor, a stepwise synthesis of methyl α-L-rhamnopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→2)- [α-D-glucopyranosyl-(1→3)]-α-L-rhamnopyranoside (CDA(E)B-OMe, 3) is described. This branched pentasaccharide constitutes a methyl glycoside representative of the repeating unit of the O-antigen of Shigella flexneri serotype 5a. Two routes to 3 were undertaken. Route 1 involved the coupling of a rhamnopyranosyl trichloroacetimidate (7) to a DA(E)B acceptor bearing an N-trichloroacetyl functionality at position 2 of residue D. Transformation of the trichloroacetamide moiety into an acetamide group was performed either by radical dechlorination or by catalytic hydrogenation. In route 2, the latter conversion was performed at the tetrasaccharide stage by Zemplén deacylation and subsequent acetylation of the free amino group. Coupling of the resulting DA(E)B to 7 gave the fully protected 2-acetamido pentasaccharide intermediate. The reactivity of the two tetrasaccharide acceptors differed, the acetamido one requiring harsher coupling conditions. Besides, when performed at the tetrasaccharide stage, conversion of the trichloroacetamide group into the desired acetamide group was rather delicate. For these reasons, route 1 was preferred. In any case, distortion of several signals in the ¹³C NMR spectra of many synthetic intermediates showed that steric hindrance had a major impact on the outcome of the glycosylation steps.