Synthesis of seven-membered iminosugars fused thiazolidin-4-one and benzthiazinan-4-one and their HIV-RT inhibitory activity

Abstract

Novel seven-membered iminosugars fused thiazolidin-4-one and benzthiazinan-4-one were conveniently synthesized by the tandem Staudinger/aza-Wittig/cyclization reaction under microwave radiation. Benzoyl group (Bz) migrations were found in the synthesis of 8c and 9b using D-galactoside or D-mannoside as starting materials, respectively, which was suggested by HMBC and X-ray. The new bi/tricyclic iminosugars 3~4(a-d) and 5(b-d) were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that all compounds except 5b could effectively inhibit RT activity. Among them, compounds 3c and 4c were the best ones with the IC50 values of RT inhibitory activities of 2.11 μM and 2.73 μM, respectively. Structure-activity relationship analysis suggested that the phenyl group in the tricyclic azasugars was beneficial for their anti-HIV RT activity. Show more