Facile, efficient, and enantiospecific syntheses of 1,1′-N-linked pseudodisaccharides as a new class of glycosidase inhibitors

This article describes an efficient synthesis of a potent trehalase inhibitor, 1,1′-N-linked pseudodisaccharide 1 (consisting of two valienamines), in 14 steps with an overall yield of 12% and a first synthesis of 2 (consisting of two 2-epi-valienamines) in 15 steps with an overall yield of 24% from (-)-quinic acid. The synthesis involves a stereospecific palladium-catalyzed coupling reaction between an allylic amine and an allylic chloride as the crucial step. The acetonide blocking groups were shown to be the best hydroxyl protecting groups, compatible with the palladium-catalyzed allylic amination reaction that afforded high yields of the 1,1′-N-linked pseudodisaccharides with a minimum amount of an elimination diene side product.