Synthesis of new (.+-.)-3,5-dihydroxypentyl nucleoside analogs from 1-amino-5-(benzyloxy)pentan-3-ol and their antiviral evaluation

Abstract

The synthesis and antiviral evaluation of a series of (.+-.)-3,5-dihydroxypentyl nucleoside analogues related to acyclic nucleoside antiviral agents are reported. All purine and pyrimidine nucleoside analogues described in this paper have been obtained from 1-amino-5-(benzyloxy)pentan-3-ol. A synthesis of this amine is reported from 1-(benzyloxy)but-3-ene after epoxidation and regiospecific diethylaluminum chloride catalyzed opening of the epoxide by trimethylsilyl cyanide. The compounds were tested in vitro in infected MRC5 and CEM cells. None of the compounds exhibited antiviral activity against HSV-1, HCMV, and HIV-1 with the exception of the guanine derivative 7, which inhibited the cytopathic effect of HSV-1 by 50% at 12.5 .mu.g/mL.