TSAO-T analogues bearing amino acids at position N-3 of thymine: synthesisand anti-human immunodeficiency virus activity

Novel analogues of the anti-HIV-l lead compound [1-[2',5'-bis-O-(tert-butyl dimethylsilyl)-beta-D-ribofuranosyl]thymine]-3'-spiro-5'-(4"-amino-1",2"-ox athiole-2',2'-dioxide) (TSAO-T) bearing different amino acids at position N -3 of thymine were prepared and evaluated as inhibitors of HIV replication. The synthesis of the target compounds was accomplished by coupling of the appropriate TSAO intermediate with a conveniently protected (L) amino acid in the presence of BOP and triethylamine, followed by deprotection of the a mino acid moiety. Several TSAO derivatives, bearing at N-3 position of the thymine base an L-amino acid retaining the free carboxylic acid, acquired a ctivity against HIV-2, in addition to their inhibitory effect on HIV-1.