Unit

UNIT 2.17 Synthesis of 5′-O-DMT-2′-O-TBS Mononucleosides Using an Organic Catalyst

  1. Sunggi Lee1,
  2. Thomas P. Blaisdell1,
  3. Pinar Kasaplar2,
  4. Xixi Sun1,
  5. Kian L. Tan1

Published Online: 24 JUN 2014

DOI: 10.1002/0471142700.nc0217s57

Current Protocols in Nucleic Acid Chemistry

Current Protocols in Nucleic Acid Chemistry

How to Cite

Lee, S., Blaisdell, T. P., Kasaplar, P., Sun, X. and Tan, K. L. 2014. Synthesis of 5′-O-DMT-2′-O-TBS Mononucleosides Using an Organic Catalyst. Current Protocols in Nucleic Acid Chemistry. 57:2.17:2.17.1–2.17.11.

Author Information

  1. 1

    Boston College, Chestnut Hill, Massachusetts

  2. 2

    Institute of Chemical Research of Catalonia, Tarragona, Spain

Publication History

  1. Published Online: 24 JUN 2014

Abstract

This unit describes a highly effective method to produce 5′-O-DMT-2′-O-TBS mononucleosides selectively using a small organic catalyst. This methodology avoids the tedious protection/deprotection strategy necessary to differentiate the 2′- and 3′-hydroxyl groups in a ribonucleoside. The catalyst was synthesized in two steps, starting from the condensation of valinol and cyclopentyl aldehyde, followed by anionic addition of N-methylimidazole. Ring closure of the amino alcohol with N,N-dimethylformamide dimethyl acetal in methanol furnishes the catalyst. All four 2′-O-TBS protected mono-nucleosides, U, ABz, GIb, and CAc, were produced in a single step using 10 to 20 mol% of the catalyst at room temperature with excellent yields and selectivity. Further transformation to phosphoramidite demonstrates the utility of this protocol in the preparation of monomers useful for automated synthesis of RNA. Curr. Protoc. Nucleic Acid Chem. 57.2.17.1-2.17.11. © 2014 by John Wiley & Sons, Inc.

Keywords:

  • 2′-O-TBS ribonucleosides;
  • protection by site-selective functionalization;
  • organocatalyst;
  • phosphoramidation