Improved synthesis of 5-hydroxymethyl-2'-deoxycytidine phosphoramidite using a 2'-deoxyuridine to 2'-deoxycytidine conversion without temporary protecting groups

Bioorg Med Chem Lett. 2011 Feb 15;21(4):1181-4. doi: 10.1016/j.bmcl.2010.12.098. Epub 2010 Dec 24.

Abstract

5-Hydroxymethylcytosine has recently been characterized as the 'sixth base' in human DNA. To enable research on this DNA modification, we report an improved method for the synthesis of 5-hydroxymethyl-2'-deoxycytidine ((5-HOMe)dC) phosphoramidite for site-specific incorporation into oligonucleotides. To minimize manipulations we employed a temporary protecting group-free 2'-deoxyuridine to 2'-deoxycytidine conversion procedure that utilizes phase transfer catalysis. The desired (5-HOMe)dC phosphoramidite is obtained in six steps and 24% overall yield from 2'-deoxyuridine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / chemistry*
  • Deoxyuridine / chemistry*
  • Electrophoresis, Capillary
  • Humans
  • Oligonucleotides / chemical synthesis*
  • Oligonucleotides / chemistry
  • Organophosphorus Compounds / chemical synthesis
  • Organophosphorus Compounds / chemistry*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • 5-hydroxymethyl-2'-deoxycytidine
  • Oligonucleotides
  • Organophosphorus Compounds
  • phosphoramidite
  • Deoxycytidine
  • Deoxyuridine