Synthesis and antiviral activity of 3′-C-branched-3′-deoxy analogues of adenosine

The synthesis of some 3′-C-branched-3′-deoxy adenine nucleosides is described. Starting from the known 3-deoxy-3-C-(hydroxymethyl)-1,2;5,6-di-O-isopropylidene-α-d-allofuranose (1), a versatile glycosylating agent, namely 1,2-di-O-acetyl-5-O-benzoyl-3-deoxy-3-C-(mesyloxymethyl)-β-d-ribofuranose (6), was prepared in three steps. Condensation of the latter with bis(trimethysilylated) N6-benzoyladenine in the presence of tin(IV) chloride gave the N9-β-nucleoside7. Compound 7 was converted into (i) 9-[3-C-(azidomethyl)-3-deoxy-β-d-ribofuranosyl]adenine (10), (ii) 9-[3-C-(azidomethyl)-2,3-dideoxy-β-d-glycero-pent-2-enofuranosyl]adenine (14) and 9-[2-azido-3-C-(azidomethyl)-2,3-dideoxy-β-d-arabinofuranosyl]adenine (15), and (iii) 9-[3-deoxy-2-O,3-C-(methylene)-β-d-ribofuranosyl]adenine (16). None of the tested nucleosides showed marked cytostatic or antiviral activity in vitro.