Formylation of carbohydrates and the evolution of synthetic routes to artificial oligosaccharides and glycoconjugates

A highly effective method for the synthesis of formyl C-glycosides is described via addition of 2-lithiothiazole or 2-lithiobenzothiazole to sugar lactones, deoxygenation of the resulting ketols, and releasing of the formyl group from the heterocyclic ring. The synthetic utility of these sugar aldehydes is demonstrated by the development of synthetic methods to more elaborate C-glycosides. These include various (1 --> 6)-C-disaccharides and some higher oligomers up to a C, C, C, C-pentasaccharide; C-glycosyl amino acid isosteres of N-glycosyl asparagines; the methylene isostere of P-D-galactosyl ceramide; linear and cylic (2 --> 1)ketoside oligomers. An alternative synthesis of ethylene-bridged glycosyl asparagine isosteres is illustrated by the use of ethynyl C-glycosides as starting materials.