A Short, Flexible Route toward 2‘-<i>C</i>-Branched Ribonucleosides

Abstract

A five-step synthesis of 2‘-C-branched ribonucleosides from commercially obtained 1,3,5-tri-O-benzoyl-α-d-ribofuranose (4) is described. The free hydroxyl group of 4 was oxidized in high yield with Dess−Martin periodane reagent. The resultant 2-ketosugar was treated with MeMgBr/TiCl4, CH2CHMgBr/CeCl3, or TMSC⋮CLi/CeCl3, and in each case addition to the ketone proceeded stereoselectively to provide 2-alkylated ribofuranosides. After conversion to the corresponding tetrabenzoyl derivatives, the 2-alkylribofuranosides were coupled to nucleobases under Vorbrüggen persilylation conditions, giving the β-nucleosides with high stereoselectivity. Deprotection with methanolic ammonia provided the title compounds in 17−49% overall yields from 4.