Total Synthesis of the Repeating Unit of Bacteroides fragilis Zwitterionic Polysaccharide A1

Zwitterionic polysaccharides isolated from commensal bacteria are endowed with unique immunological properties and are emerging as immunotherapeutic agents as well as vaccine carriers. Reported herein is a total synthesis of the repeating unit of Bacteroides fragilis zwitterionic polysaccharide A1 (PS A1). The structurally complex tetrasaccharide unit contains a rare sugar 2-acetamido-4-amino-2,4,6-trideoxy-n-galactose (AAT) and two consecutive 1,2-cis glycosidic linkages. The repeating unit was efficiently assembled by rapid synthesis of D-galactosarnine and AAT building blocks from cheap and abundant n-mannose via a one-pot S(N)2 displacement of 2,4-bistriflates and installation of all of the glycosidic bonds in a highly stereoselective manner. The total synthesis involves a longest linear sequence of 17 steps with 3.47% overall yield.

Automated summary

The total synthesis of the repeating unit of Bacteroides fragilis zwitterionic polysaccharide A1 (PS A1) was achieved through efficient synthesis of D-galactosamine and AAT building blocks from cheap and abundant n-mannose, followed by highly stereoselective installation of all glycosidic bonds. This involved a 17-step longest linear sequence with an overall yield of 3.47%.