Open AccessSynthesis 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 phosphotriesier procedures
Author(s) -
W. Dabkowslri,
Z. Skrzypczyński,
J. Micnalshi,
Norbert Piel,
Larry W. McLaughlin,
Friedrich Cramer
Publication year - 1984
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/12.23.9123
Subject(s) - nucleoside , nucleophile , organic chemistry , phosphodiester bond , derivative (finance) , phosphoric acid , sulfonic acid , chemistry , combinatorial chemistry , catalysis , stereochemistry , biochemistry , rna , financial economics , economics , gene
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.