Exploring the role of the 5 '-position of TSAO-T. Synthesis and anti-HIV evaluation of novel TSAO-T derivatives

Various analogues of the anti-HIV-1 agent TSAO-T, [1-[2',5'-bis-O-(tert-but yldimethylsilyl)-beta -D-ribofuranosyl]thymine]-3'-spiro-5"-(4"-amino- 1",2 "-oxathiole-2",2"-dioxide) have been synthesized in which the 5'-TBDMS grou p has been replaced by alkyl-, alkenyl- or aromatic ether groups, substitut ed amines. carbamoyl or (thio)acyl groups. The compounds synthesized were e valuated for their inhibitory effect on HIV-1 and HIV-2 replication in cell culture. Replacement of the 5'-TBDMS group by an acyl, aromatic or a cycli c moiety markedly diminish or even eliminate the anti-HIV activity. However , the presence at that position of an alkyl or alkenyl chain, partially ret ain antiviral activity. These observations suggest that the 5'-TBDMS group of the TSAO molecule plays a crucial role. (C) 2001 Elsevier Science B.V. A ll rights reserved.