Synthesis of 3′-O-phosphonomethyl nucleosides with an adenine base moiety

A synthetic scheme has been developed for the synthesis of 2′-deoxythreose phosphonate nucleosides from β-hydroxy-γ-butyrolactone and of 2′-azido erythrose phosphonate nucleosides from dihydroxydihydrofuran-1-one. In addition several α-l-arabinofuranose phosphonate nucleosides were synthesized starting from protected α-d-galactofuranose. Unfortunately, none of the synthesized compounds show activity in an HIV-1 assay. One of these compounds, a locked phosphonate nucleoside, was evaluated (as diphosphate) for its potential to be incorporated into DNA using HIV-1 reverse transcriptase.

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