Synthesis of (2'S)- and (2'R)-2'-deoxy-2'-[(2-methoxyethoxy)amino] pyrimidine nucleosides and oligonucleotides

Chem Biodivers. 2004 Oct;1(10):1537-45. doi: 10.1002/cbdv.200490114.

Abstract

Syntheses of specified 2'-modified nucleosides were achieved: a) via oximation of the 5',3'-blocked 2'-oxocytidine, followed by reduction, or b) by intramolecular nucleophilic addition of 3'-(2-methoxyethoxy)carbamate to the 2'-position with opening of O(2),2'-anhydrouridine. For the first time, 3'-phosphoroamidites of these 2'-modified nucleosides were successfully incorporated into oligonucleotides by solid-phase synthesis. Incorporation of 2'-modified nucleotides into oligodeoxyribonucleotides had a negative effect on the duplex T(m) values with the DNA or RNA complements. Nevertheless, modified nucleotides have shown good target recognition; the (S)-isomer binds preferably to RNA and the (R)-isomer to DNA. Both modified nucleosides significantly increased nuclease resistance of the oligodeoxyribonucleotides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Nucleic Acid Conformation
  • Oligonucleotides / chemical synthesis*
  • Oligonucleotides / isolation & purification
  • Persea
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Pyrimidine Nucleosides / chemical synthesis*
  • Pyrimidine Nucleosides / isolation & purification
  • Snake Venoms / chemistry
  • Snake Venoms / isolation & purification
  • Stereoisomerism

Substances

  • Oligonucleotides
  • Plant Extracts
  • Pyrimidine Nucleosides
  • Snake Venoms