Synthesis of the 5′-phosphonate of 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol [S,S-IsoddA]

Abstract

4(S)-(6-Amino-9H-purin-9-yl)tetrahydrofuran-2(S)-ylmethyl phosphonic acid, a 5′-C-phosphonate analog of the potent anti-HIV compound S,S-IsoddA, was synthesized in order to bypass the critical initial intracellular phosphorylation. Key phases in this multistep synthesis were the Arbuzov reaction of the 5-iodofuranose with triethylphosphite and the Mitsunobu/coupling reaction of the phosphonate with adenine. The structure of the final product was confirmed by HRMS and multinuclear NMR data.