Synthesis of unsaturated 4′-azido pyranosyl thymines as potential antiviral and anti-HIV agents

Abstract

Condensation of thymine with diacetyl-D-xylal and triacetyl-D-glucal afforded the unsaturated nucleosides 1, 6 and 7. After deacetylation and selective protection of the primary hydroxy groups in the case of the glucose derivatives, these compounds were either submitted to Mitsunobu reaction with hydrazoic acid to give the azides 4, 14 and 15, or oxidised with PDC–molecular sieves to give the unsaturated keto nucleosides 3, 12 and 13. Reduction of the azides 4, 14 and 15 afforded the amino derivatives 5, 18 and 19. Oxidation of the latter two compounds gave the aminouronate nucleosides 20 and 21. Preliminary testing on various virus models, including HIV, showed the ketones 3, 12 and 13 to be the most active compounds of this series.