Synthesis of nucleic acid methylphosphonates via the 1-hydroxybenzotriazole phosphotriester approach.
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.
Marugg
J E
JE
de Vroom
E
E
Dreef
C E
CE
Tromp
M
M
van der Marel
G A
GA
van Boom
J H
JH
D055598:Chemical Phenomena; D002621:Chemistry; D015226:Dinucleoside Phosphates; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation; D009712:Nucleotides, Cyclic / Q000138:chemical synthesis*; D009841:Oligonucleotides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds; D010766:Phosphorylation; D013237:Stereoisomerism; D014230:Triazoles
D015226:Dinucleoside Phosphates; D007202:Indicators and Reagents; D009712:Nucleotides, Cyclic; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D014230:Triazoles; C048424:methyl-O,O-bis(1-benzotriazolyl)phosphate; C032627:methylphosphonic acid