Solid support synthesis of oligothymidylates using phosphorochloridates and 1-alkylimidazoles.
A study of the synthesis of oligothymidylates via phosphotriester intermediates on a polystyrene support is described. The sequence involves condensation of a phenyl nucleoside-3' -phosphorochloridate with the 5'-hydroxyl group of the carrier bound oligonucleotide derivative in the presence of 1-methylimidazole. Conditions for preparation of the phenyl nucleo-side phosphorochloridate as well as for the condensation on the support are discussed. d-TpTpTpT was obtained in 31% overall yield from carrier bound thymidine in one series of experiments, and d-TpTpTpTpT was obtained in 9% yield in another. The cycle for addition of one nucleotide unit can be completed in about six hours.
D002713:Chlorine; D007093:Imidazoles; D009841:Oligonucleotides / Q000138:chemical synthesis*; D017976:Phosphorus Acids; D011137:Polystyrenes; D013942:Thymine Nucleotides / Q000138:chemical synthesis
D007093:Imidazoles; D009841:Oligonucleotides; D017976:Phosphorus Acids; D011137:Polystyrenes; D013942:Thymine Nucleotides; D002713:Chlorine