Reactive intermediates in the H-phosphonate synthesis of oligonucleotides.
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.
Department of Chemical and Biological Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Nicholas
N
Powles
John
J
Atherton
Michael I
MI
Page
D060326:Chemistry Techniques, Synthetic; D006859:Hydrogen / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry*
D009841:Oligonucleotides; D063065:Organophosphonates; D006859:Hydrogen