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

Abstract

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) N 6-benzoyladenine in the presence of tin(IV) chloride gave the N 9- β-nucleoside 7. 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.