Concise synthesis of (S)-7-Hydroxy-5-aza-8a- epi - D -swainsonine from a d -erythrose derivative

Abstract

A five-step synthesis of (S)-7-hydroxy-5-aza-8a-epi-D-swainsonine [(3S,4S,4aS,5S,6R)-octahydropyrrolo[1,2-b]pyridazine-3,4,5,6- tetraol] was accessed in good overall yield from readily available D-erythrosyl benzylidene acetal buta-1,3-diene. The key step of the reaction sequence is a full stereoselective Diels Alder cycloaddition between the diene and dienophile: diethyl azodicarboxylate (DEAD) or di-tert-butyl azodicarboxylate (DBAD). The cycloadducts were further transformed into the title 5-aza-indolizidine. Optimized procedures were obtained for the synthesis of intermediates and products.