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Russian Chemical Bulletin

, Volume 44, Issue 1, pp 167–171 | Cite as

A new approach to the synthesis of cilastatin, an inhibitor of renal dipeptidase

  • M. G. Vinogradov
  • L. N. Kalgorodova
  • G. V. Chel'tsova-Bebutova
  • L. S. Gorshkova
  • E. K. Starostin
  • G. I. Nikishin
  • A. V. Ignatenko
  • E. A. Shapiro
Chemistry of Natural Compounds and Bioorganic Chemistry

Abstract

A convenient preparative synthesis of cilastatin, an inhibitor of renal dipeptidase used in drugs with the antibiotic imipenem, has been elaborated. The key intermediate in this synthesis is 2-amino-7-chloroheptanoic acid prepared by oxidative cleavage of cycloheptanone followed by bromination of 7-chloroheptanoyl chloride with subsequent amination of the 2-bromo-7-chloroheptanoic acid thus formed. All of the stages of the new synthesis are easily performed, as is the isolation of the intermediate products, and they do not require any organometallic reagents.

Key words

cilastatin (R)-cysteine 7-chloroheptanoic acid 2-amino-7-chloro-2-heptenoic acid 2,2-dimethylcyclopropanecarbonyl chloride oxidation bromination amination cyclopropanation 

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Copyright information

© Plenum Publishing Corporation 1995

Authors and Affiliations

  • M. G. Vinogradov
    • 1
  • L. N. Kalgorodova
    • 1
  • G. V. Chel'tsova-Bebutova
    • 1
  • L. S. Gorshkova
    • 1
  • E. K. Starostin
    • 1
  • G. I. Nikishin
    • 1
  • A. V. Ignatenko
    • 1
  • E. A. Shapiro
    • 1
  1. 1.N. D. Zelinsky Institute of Organic ChemistryRussian Academy of SciencesMoscowRussian Federation

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