P. Miller, C. Agris, M. Blandin
Aug 11, 1983
Citations
0
Influential Citations
22
Citations
Journal
Nucleic acids research
Abstract
Methylphosphonic dichloride was used to prepare protected deoxyribonucleoside 3'-methylphosphonate beta-cyanoethyl esters, d-[(MeO)2Tr]NpCNEt, and protected oligonucleoside methylphosphonates in solution. Reaction of d-[(MeO)2Tr]N with methylphosphonic dichloride gives d-[(MeO)2Tr]NpCl. The phosphonylation and subsequent esterification or condensation reactions are each complete within 60 min. The products are readily purified by "flash chromatography" on silica gel columns. d-[(MeO)2Tr]NpCl, or its tetrazole derivative, d-[(MeO)2Tr]Nptet, were tested as intermediates for the synthesis of oligothymidine methylphosphonates on a silica gel polymer support. The average yield per coupling step was 76% and did not increase with addition of more d-[(MeO)2Tr]TpCl. The formation of (5'-5') linked thymidine dimers indicated that the thymidine monomers are clustered closely together on the support. When N is ibuG, the yield for the coupling step on the support is very low. This may be due to steric hindrance of the 3'-phosphonate group by the N-2 isobutryl protecting group.