Stereoselective Synthesis of Ribonucleoside 3′,5′-Cyclic Methyl(phenyl)phosphonates and Phosphonothioates

Abstract

Monophosphonylation of 2′-protected ribonucleosides (i.e. 2′-O-THP-uridine and 2′-O-THP-N ⁶-levulinoyl-adenosine) with the bifunctional reagents bis[(6-trifluoromethyl)benzotriazol-1-yl] methyl(phenyl)phosphonates or the analogous phosphonothioates, and subsequent addition of N-methylimidazole, gave the chirally pure 3′,5′-cyclic methyl(phenyl)phosphonate or phosphonothioate derivatives, respectively. Deblocking of the fully protected compounds yielded, as evidenced by X-ray analysis, the corresponding pure Sp-diastereoisomers.