Synthesis and reactions of a nucleoside derivative of phosphoric sulfonic anhydride. Studies related to the mechanisms of coupling reactions in the chemical synthesis of oligodeoxyribonucleotides by phosphotriester procedures.
The synthesis of a model compound, diphenylphosphoric toluene-p-sulfonic anhydride, an arylsubstituted phosphoric sulfonic mixed anhydride, is described. Using the same procedure a thymidyl substituted derivative was prepared. The phosphoric sulfonic anhydride is the presumed intermediate in oligonucleotide coupling reactions involving phosphodiester activation by arenesulfonyl derivatives. This mixed anhydride reacts with a variety of nucleophiles. It can be converted to phophotriester derivatives in the presence of simple alcohols. Phosphotriester formation using the 5'-hydroxyl of a thymidine derivative requires additionally a catalyst such as N-methylimidazole. The reactive intermediate produced upon the addition of N-methylimidazole to the phosphoric sulfonic anhydride has been observed spectroscopically using 31P-NMR.
D055598:Chemical Phenomena; D002621:Chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis*; D009841:Oligonucleotides / Q000138:chemical synthesis*; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives
D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D009946:Organothiophosphorus Compounds; C043840:diphenylphosphoric toluene-4-sulfonic anhydride; D013936:Thymidine