Syntheses of two 5-hydroxymethyl-2'-deoxycytidine phosphoramidites with TBDMS as the 5-hydroxymethyl protecting group and their incorporation into DNA

J Org Chem. 2011 May 20;76(10):4182-8. doi: 10.1021/jo200566d. Epub 2011 Apr 14.

Abstract

5-Hydroxymethylcytosine (5-hmC) is a newly discovered DNA base modification in mammalian genomic DNA that is proposed to be a major epigenetic mark. We report here the syntheses of two new versions of phosphoramidites III and IV from 5-iodo-2'-deoxyuridine in 18% and 32% overall yields, respectively, with TBDMS as the 5-hydroxyl protecting group. Phosphoramidites III and IV allow efficient incorporation of 5-hmC into DNA and a "one-step" deprotection procedure to cleanly remove all the protecting groups. A "two-step" deprotection strategy is compatible with ultramild DNA synthesis, which enables the synthesis of 5hmC-containing DNA with additional modifications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / analogs & derivatives
  • Cytosine / analogs & derivatives*
  • Cytosine / chemistry
  • DNA / chemical synthesis
  • DNA / chemistry*
  • Organophosphorus Compounds / chemical synthesis*
  • Organophosphorus Compounds / chemistry*
  • Siloxanes / chemistry*
  • Styrenes / chemistry*

Substances

  • 4-(tert-butyldimethylsiloxy)styrene
  • Organophosphorus Compounds
  • Siloxanes
  • Styrenes
  • phosphoramidite
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine
  • Cytosine
  • DNA