Reactive intermediates in the H-phosphonate synthesis of oligonucleotides

Nicholas Powles, John Atherton, Michael I. Page

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The formation of H-phosphonate diesters is an important step in the synthesis of oligonucleotides. Using diphenylchlorophosphate as the activator for the coupling step is often accompanied by side reactions as a result of self 'capping' and other reactions of the reactive intermediate. In the absence of base, the activation of ethyl H-phosphonate with diphenylchlorophosphate probably occurs through the intermediate formation of bis diethyl pyro-di-H-phosphonate rather than the expected diphenyl ethyl pyro-H-phosphonate. Pyridine acts as a nucleophilic catalyst converting diphenylchlorophosphate to its pyridinium adduct. Several side and unwanted reactions are quantified so that conditions to minimise these can be identified.

LanguageEnglish
Pages5940-5947
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume10
Issue number30
DOIs
Publication statusPublished - 14 Aug 2012

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Organophosphonates
oligonucleotides
Oligonucleotides
synthesis
adducts
pyridines
activation
catalysts
Chemical activation
Catalysts

Cite this

Powles, Nicholas ; Atherton, John ; Page, Michael I. / Reactive intermediates in the H-phosphonate synthesis of oligonucleotides. In: Organic and Biomolecular Chemistry. 2012 ; Vol. 10, No. 30. pp. 5940-5947.
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Reactive intermediates in the H-phosphonate synthesis of oligonucleotides. / Powles, Nicholas; Atherton, John; Page, Michael I.

In: Organic and Biomolecular Chemistry, Vol. 10, No. 30, 14.08.2012, p. 5940-5947.

Research output: Contribution to journalArticle

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