A New Approach to 3′-Amino-3′-deoxynucleosides. Synthesis of 9-(3-Amino-3-deoxy-α-L-ribofuranosyl)adenine

Abstract

Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-nitro-α-D-glucopyranoside (1) was acetolyzed to give 1,2,3,4-tetra-O-acetyl-6-deoxy-6-nitro-α-D-glucopyranose (2). Compound 2 (or alternatively, 6-deoxy-1,2-O-isopropylidene-6-nitro-α-D-glucofuranose 4) was converted into 2,3,4-tri-O-acetyl-6-deoxy-6-nitro-α- D-glucopyranosyl bromide (3) which was condensed with chloromercuri 6-benzamidopurine. De-O-acetylation of the condensation product 5 afforded 6-benzamido-9-(6-deoxy-6-nitro-β-D-glucopyranosyl)purine (6) which could be hydrogenated to the corresponding 6′-amino nucleoside 7. Periodate oxidation of 6 followed by internal Henry cyclization and borohydride reduction gave 6-benzamido-9-(3-deoxy-3-nitro-α-L-ribofuranosyl)purine (10) which upon catalytic hydrogenation and subsequent de-N-benzoylation produced the title compound, 12. The sensitivity of certain nitro intermediates towards alkali is commented upon.