Diastereofacial Selective Addition of Ethynylcerium Reagent and Barton−McCombie Reaction as the Key Steps for the Synthesis of <i>C</i>-3‘-Ethynylribonucleosides and of <i>C</i>-3‘-Ethynyl-2‘-deoxyribonucleosides

Abstract

We describe the preparation of 3'-alkynyluridine 4a and -adenosine 4b and of 3'-alkynyl-2'-deoxyuridine 16a and -adenosine 16b starting from the corresponding nucleosides. The desired stereochemistry of the C-3' tertiary alcohol was obtained by reaction of an ethynylcerium-lithium reagent on a 3'-ketonucleoside with the hydroxyl group at C-5' unprotected. The 2'-deoxygenation was performed by a Barton-McCombie reaction under appropriate conditions where the addition of tin hydride to the triple bond was suppressed. Evaluation of the anti-HIV activity of the C-3' modified nucleosides is reported.