Open AccessSynthesis of nucleic acid methylphosphonates via the 1-hydroxybenzotriazole phoaphotriester approach
Author(s) -
J. E. Marugg,
Erik de Vroom,
C.E. Drecf,
M. Tromp,
G.A. van der Mard,
Jacques H. van Boom
Publication year - 1986
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/14.5.2171
Subject(s) - biology , nucleic acid , dna , biochemistry , computational biology , virology , microbiology and biotechnology
Dinucleoside methylphosphonates can easily be prepared starting from properly protected d-nucleosides and the bifunctional phosphorylating reagent methyl-O,O-bis(1-benzotriazolyl)phosphate. Separation of the diastereoisomers of 5'-DMTR-d-Ap(Me)T-3'-lev affords optically pure dinucleoside methylphosphonates which, after removal of the 3'-levulinoyl group, have been used for the synthesis of the two optically pure diastereoisomers of the hexamer d-CpGpAp(Me)TpCpG. Further, a one-pot procedure for the preparation of uridine-3',5'-cyclic methylphosphonate will be described. We also found that 3',5'-methylphosphonate linkages in RNA are not stable towards mild acid treatment.