1,7-DIDEAZA-2',3'-DIDEOXYADENOSINE - SYNTHESES OF PYRROLO[2,3-B]PYRIDINE 2',3'-DIDEOXYRIBOFURANOSIDES AND PARTICIPATION OF PURINE N(1) DURING HIV-1 REVERSE-TRANSCRIPTASE INHIBITION

Abstract

The syntheses of 1,7-dideaza-2',3'-dideoxyadenosine (1) and related pyrrolo[2,3-b]pyridine 2',3'-dideoxyribo- and 2',3'-didehydro-2',3'-dideoxyribonucleosides (see 2-5) are described. As starting materials, 2'-deoxyribonucleosides 6 or 7 were used. The 3'-OH group was removed by Barton deoxygenation or via mesylation followed by elimination and catalytic hydrogenation. Compound 1 was also obtained from the direct glycosylation of 4-nitro-H-1-pyrrolo[2,3-b]pyridine (17) with the 2,3-dideoxyribofuranosyl chloride 18. The triphosphate 25 of 1 showed only marginal activity against HIV-1 reverse transcriptase, indicating that purine N(1) is required for the inhibitory activity of the parent 2',3'-dideoxyadenosine.