Synthesis of tetracyclic azasugars fused benzo[e][1,3]thiazin-4-one by the tandem Staudinger/aza-Wittig/cyclization and their HIV-RT inhibitory activity.

Azasugar aldehydes 6a and 6b containing azido groups were prepared from D-mannose. Three novel tetracyclic azasugars fused benzo[e][1,3]thiazin-4-one 9a-1, 9a-2 and 9a-3 were conveniently synthesized from 6a by the tandem intramolecular Staudinger/aza-Wittig/cyclization reaction under microwave radiation. Two unexpected elimination compounds 8b-1 and 8b-2 were achieved as the main products from 6b in the same processes. The newly synthesized azasugars were examined for their HIV reverse transcriptase (RT) inhibitory activities. The results showed that all the tested compounds could effectively inhibit RT activity. Among them, compound 8b-1 with the protective group (isopropylidene group) was the best one with the IC value of 0.76 μM. The structure activity relationship analysis suggested that improvement of the molecular hydrophilicity might be beneficial for their anti-HIV RT activities.