NEW NEPLANOCIN ANALOGS .7. SYNTHESIS AND ANTIVIRAL ACTIVITY OF 2-HALODERIVATIVES OF NEPLANOCIN-A

The syntheses and the antiviral activities of 2-halo derivatives of ne planocin A (1b,c), (6'R)-6'-C-methylneplanocin A (2b), and dehydroxyme thylneplanocin A (3b,c) are described. S(N)2 reaction of the known cyc lopentenyl units 12 and 13 with 2-haloadenines under basic conditions gave the protected carbocyclic nucleosides 14b,c and 15b,c, respective ly. Starting from the cyclopentenone derivative 5, the optically activ e tosyloxycyclopentene derivative 11 was prepared, which was similarly condensed with 2-fluoroadenine to give the protected (6'R)-6'-C-methy l derivative 16b. Deprotection of these compounds afforded the target 2-halo derivatives of neplanocin A. Of these new compounds, 2-fluorone planocin A (1b) showed an antiviral potency and a spectrum that was co mparable to that of neplanocin A (1a). It was particularly active agai nst vaccinia virus, vesicular stomatitis virus, parainfluenza virus, r eovirus, arenaviruses (Junin, Tacaribe), and human cytomegalovirus, i. e., those viruses that fall within the purview of the S-adenosyl-L-hom ocysteine hydrolase inhibitors.