Synthesis of novel 3'-hydroxymethyl 5'-deoxythreosyl phosphonic acid nucleoside analogues as potent antiviral agents.

A very efficient synthetic route to novel 3'-hydroxymethyl 5'-deoxythreosyl phosphonic acid nucleosides was described. The discovery of threosyl phosphonate nucleoside (PMDTA, EC(50) = 2.53 μM) as a potent antihuman immunodeficiency virus (anti-HIV) agent has led to the synthesis and biological evaluation of 3'-modified 5'-deoxy versions of the threosyl phosphonate nucleosides. 3'-Hydroxymethyl 5 '-deoxythreosyl phosphonic acid nucleoside analogues 15, 19, 24, and 28 were synthesized from 1,3-dihydroxyacetone and tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 19 exhibits moderate in vitro anti-HIV-1 activity (EC(50) = 10.2 μM).