Efficient synthesis of methyl 3,5-Di-O-benzyl-α-D-ribofuranoside and application to the synthesis of 2'-C-β-Alkoxymethyluridines

Methyl 3,5-di-O-arylmethyl-alpha-D-ribofuranosides have been used extensively as synthons to construct 2'-C-branched ribonucleosides. Herein, we describe efficient access to methyl 3,5-di-O-arylmethyl-alpha-D-ribofuranosides (aryl: 2-ClC6H4, 3-ClC6H4, 4-ClC6H4, 4-BrC6H4, 2,4-Cl2C6H3, Ph) in 72-82% yields from methyl D-ribofuranoside. We also demonstrate efficient access to the versatile precursor methyl 3,5-di-O-benzyl-alpha-D-ribofuranoside (3f) and the synthesis of 2'-C-beta-methoxymethyl- and 2'-C-beta-ethoxymethyluridine in six steps from 3f with overall yields of 18% and 32%, respectively.