Carbohydrate Homologation by the Use of 2-(Trimethylsilyl)thiazole. Preparative Scale Synthesis of Rare Sugars: l-Gulose, l-Idose, and the Disaccharide Subunit of Bleomycin A2

Abstract

The well established one-carbon homologation method of protected monosaccharides employing 2-(trimethylsilyl)thiazole (2-TST) as a formyl anion equivalent has been used for high yield and multigram scale synthesis of the title rare hexoses from l-xylose. Thus, l-gulose has been obtained by stereoselective anti-addition of 2-TST to aldehydo-l-xylose diacetonide followed by thiazole to formyl conversion of the resulting alcohol. The inversion of configuration at C-1 of this alcohol by an oxidation−reduction sequence prior to the aldehyde releasing from thiazole led to l-idose. The same alcohol was readily elaborated into 1,3,4,6-tetra-O-acetyl-l-gulopyranose whose highly stereoselective glycosidation coupling with 3-O-carbamoyl-2,4,6-tri-O-acetyl-α-d-mannosyl diethyl phosphate afforded the same peracetylated disaccharide subunit employed by Boger and Honda in the total synthesis of the antibiotic bleomycin A2.