Universal solid supports for the synthesis of oligonucleotides via a transesterification of H-phosphonate diester linkage

J Org Chem. 2005 Nov 11;70(23):9198-206. doi: 10.1021/jo051172n.

Abstract

[Structure: see text]. Three universal solid supports exhibiting an hydroxyl function were prepared. The introduction of a first H-phosphonate diester linkage which was kept throughout the elongation allowed the release of 3'-hydroxyl oligonucleotides by a transesterification mechanism. The transesterification was performed in a few minutes with either amino alcohols or K2CO3/methanol. Starting from a hydroxyl solid support, tandem oligonucleotides were synthesized and the solid support was easily recyclable. This strategy was extended to the release of an oligonucleotide from the solid support by a nonbasic treatment opening the way to the synthesis of base-sensitive oligonucleotides thanks to the selective deprotection of a hydroxyl in beta of the H-phosphonate diester linkage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Esterification
  • Esters / chemistry*
  • Oligonucleotides / chemical synthesis*
  • Organophosphonates / chemistry*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Esters
  • Oligonucleotides
  • Organophosphonates