An expeditious synthesis of 3′-α-carboxymethyl-2′-O-methyl ribonucleosides

3'-alpha-Carboxymethyl-2'-O-methyl ribonucleosides, which are important building blocks for the construction of high affinity amide modified antisense oligonucleotides, have been synthesized from the corresponding 2'-O-methyl ribonucleosides via catalytic hydrogenation of their 3'-deoxy 3'-methoxycarbonyl-methylidene derivatives. Reduction of the olefinic double bond proceeds in good to excellent yields and with alpha/beta-product ratios > 9/1. (C) 1999 Elsevier Science Ltd. All rights reserved.