Developments in Syntheses of Oligodeoxyribonucleotides and Their Organic Derivatives

Robert L. Letsinger, Kelvin K. Ogilvie, Paul S. Miller

Research output: Contribution to journalArticle

Abstract

The β-cyanoethyl phosphotriester approach to the synthesis of oligonucleotides is shown to be general for deoxyribonucleosides by the synthesis of MTrTp(ce)dCBz, MTrTp(ce)dABz, and MTrTp(ce)dGAc and the conversion of these derivatives to TpdC, TpdA, and TpdG, respectively. The utility of the synthetic scheme is also extended by the observation that β-benzoylpropionyl serves as a protecting group for the 3ʹ-O of nucleosides employed in the condensation reaction. This group, which prevents the formation of isomers with 3ʹ-3ʹ-inter-nucleotide hnks, can be removed selectively with hydrazine in pyridine-acetic acid. The chemistry is illustrated with the synthesis of the β-cyanoethyl ester of 5ʹ-O-(p-monomethoxytrityl)thymidylyl-(3ʹ-5ʹ)-3ʹ-O-β-benzoyl-propionyl)thymidine and the conversion of this compound to higher molecular weight oligonucleotide derivatives, from which TpTpT and TpTpdC are prepared. With the aid of the β-benzoylpropionyl protecting group, intermediates can be obtained which enable one to use the phosphotriester approach to join preformed blocks containing two or three nucleoside units. The synthesis of TpTpTpT and TpTpTpTpTpT by this method is described.

Original languageEnglish (US)
Pages (from-to)3360-3365
Number of pages6
JournalJournal of the American Chemical Society
Volume91
Issue number12
DOIs
StatePublished - Jun 1969

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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