Chemical synthesis of the pentasaccharide related to the repeating unit of the O-antigen of Enterobacter cloacae G2277

Abstract

A practical and highly efficient total synthesis of the pentasaccharide related to the O-antigen of Enterobacter cloacae G2277, the causative agent of nosocomial infection, has been accomplished in the form of its 4-methoxyphenyl glycoside. The unique pentasaccharide, →2)-α-l-Rhap-(1→2)-α-l-Rhap-(1→2)-α-l-Rhap-(1→4)-α-d-GalpA-(1→3)-α-d-GlcpNAc-(1→, was assembled by a [3+2] convergent approach as well as a sequential assembly of five rationally protected monosaccharide building blocks. In the convergent approach, α-d-Galp-(1→3)-α-d-GlcpNAc disaccharide was synthesized with a potential site for the uronic acid and the α-l-Rhap-(1→2)-α-l-Rhap-(1→2)-α-l-Rhap trisaccharide trichloroacetimidate was glycosylated to form the protected pentasaccharide in good yield. A TEMPO-mediated late stage oxidation of 6-OH of the galactose moiety resulted the characteristic uronic acid. Finally, global deprotection gave the target pentasaccharide. Both strategies were found to be equally efficient in respect to the yield of the target pentasaccharide derivative.