Synthesis of a potent inhibitor of HIV reverse transcriptase

Abstract

The newly synthesised P_β,–P_γ-difluoromethylenebisphosphonate analogue 2 of nor-carbovir triphosphate is a potent inhibitor of HIV reverse transcriptase; it also exhibits a greatly enhanced stability to dephosphorylation, in foetal blood serum, relative to AZTTP and other nucleoside triphosphates.

References

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8. Selected data for 2: ν_max(KBr)/cm^–1 1269 (P=O); λ_max(H₂O)/nm 252.0; δ_H(400 MHz, D₂O) 1.89 (1 H, dt, J 15.6, 4.4, 5′-βH), 2.97 (1 H, dt, J 14.0, 7.2, 5′-αH), 3.84 (2 H, d, J 9.2, PCH₂), 4.76–4.81 (1 H, br, 4′-H), 5.28–5.0 (1 H, br, 1′-H), 6.07–6.11 (1 H, m, 2′-H), 6.33–6.38 (1 H, m, 3′-H), 7.75–7.87 (1 H, br, 8-H); δ_F(376 MHz, D₂O) 42.40–42.90 (br, CF₂); δ_P(162 MHz, D₂O)–1.69 (br, P_β), 3.90 (br, P_γ), 11.44 (d, J 31.0, P_α); m/z(ES) 522 (6%, MH⁺), 328 (15, M – CH₂F₂O₄P₂). For 3: ν_max(KBr)/cm^–1 1236 (P=O); δ_P(162 MHz, D₂O) 2.44 (br, P_β), 9.61 (br, P_γ), 10.34 (d, J 29.0, P_α); m/z(ES) 504 (57%, MH⁺), 328 (100, M – CFH₃O₄P₂). For 4: ν_max(KBr)/cm^–1 1216 (P=O); δ_P(162 MHz, D₂O) 15.97 (1P, br, P_β), 10.08 (2P, br, P_α and P_γ); m/z(ES) 486 (35%, MH⁺), 328 (100, M – CH₄O₄P₂).