Stability of the 6,14‐endo‐ethanotetrahydrooripavine analgesics: Acid‐catalyzed rearrangement of buprenorphine

E. J. Cone, C. W. Gorodetzky, W. D. Darwin, W. F. Buchwald

Research output: Contribution to journalArticle

Abstract

Buprenorphine (I), a member of the 6,14‐endo‐ethanotetrahydrooripavine series of analgesics, undergoes an acid‐catalyzed rearrangement reaction when exposed to acid and heat. The product was shown by 1H‐NMR and GC‐MS to have undergone overall elimination of a molecule of methanol with concurrent formation of a tetrahydrofuran ring at C(6)–C(7) of I. Short‐term stability studies across a wide range of pH and temperature conditions indicate that I is stable in aqueous solution at pH > 3 for 24 h at 36–38°C. Under the more extreme conditions of the autoclave, significant loss of I occurred. Long‐term stability studies (10 weeks) of I in aqueous solution (pH 1 and pH 5) at 0–4°C and 26–28°C indicate only minor conversion (4%) to the rearrangement product. Eight other 6,14‐endo‐ethanotetrahydrooripavine derivatives were subjected to extremes of acid (pH 0) and temperature (autoclave) to determine if similar rearrangement reactions occur. GC‐MS indicated that hydrolysis products were produced whose spectra were consistent with the proposed rearrangement structures.

Original languageEnglish (US)
Pages (from-to)243-246
Number of pages4
JournalJournal of Pharmaceutical Sciences
Volume73
Issue number2
DOIs
StatePublished - Feb 1984

Keywords

  • Analgesics—6,14‐endo‐ethanotetrahydrooripavine series
  • Buprenorphine—6,14‐endo‐ethanotetrahydrooripavine analgesics, stability
  • Stability—buprenorphine and other 6,14‐endo‐ethanotetrahydrooripavine analgesics
  • acid‐catalyzed structural rearrangement
  • acid‐catalyzed structural rearrangement
  • acid‐catalyzed structural rearrangement
  • buprenorphine
  • stability

ASJC Scopus subject areas

  • Pharmaceutical Science

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