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

• Published in: Tetrahedron letters Vol. 40; no. 10; pp. 1873 - 1876
• Main Authors: von Matt, Peter, Lochmann, Thomas, Kesselring, Rudolf, Altmann, Karl-Heinz
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 05-03-1999
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/S0040-4039(99)00147-1

3′-α-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 α/β-product ratios > 9/1.
5′-O-DMTr-protected 3′-α-carboxymethyl-2′-O-methyl ribonucleosides and the corresponding pentafluorophenyl have been synthesized from the corresponding 2′-O-methyl ribonucleosides.