Study of the relative lactonization rates of pilocarpic acid and isopilocarpic acid in acidic media

William N. Charman, Louise E. McCrossin, Nancy L. Pochopin, Sharon L.A. Munro

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The rate of specific acid catalyzed lactonization of pilocarpic acid and issopilocarpic acid at acidic pH has been studied by following the progress of the reaction by HPLC. A 17.5-fold difference in the rate of lactonization to the corresponding parent lactone was observed in favor of isopilocarpic acid. The observed differences in the rates of lactonization were rationalized through application of molecular modelling and molecular orbital calculations. Parameters studied were the calculated heats of formation, bond lengths and appropriate torsion angles for both pilocarpine and isopilocarpine. From these studies of the end products of the lactonization reactions, it appears that differences in the planarity of the lactone ring and its consequent effect on the formation of a reaction intermediate are possibly responsible for the different rates of lactonization.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalInternational Journal of Pharmaceutics
Issue number1-3
Publication statusPublished - 8 Dec 1992
Externally publishedYes


  • Isopilocarpine
  • Lactonization kinetics
  • Molecular modeling
  • Pilocarpine

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