Issue 30, 2012

Reactive intermediates in the H-phosphonate synthesis of oligonucleotides

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.

Graphical abstract: Reactive intermediates in the H-phosphonate synthesis of oligonucleotides

Supplementary files

Article information

Article type
Paper
Submitted
19 pro 2011
Accepted
24 tra 2012
First published
07 lip 2012

Org. Biomol. Chem., 2012,10, 5940-5947

Reactive intermediates in the H-phosphonate synthesis of oligonucleotides

N. Powles, J. Atherton and M. I. Page, Org. Biomol. Chem., 2012, 10, 5940 DOI: 10.1039/C2OB07130D

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