Stability of the 6,14-endo-ethanotetrahydrooripavine analgesics: acid-catalyzed rearrangement of buprenorphine.
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 greater than 3 for 24 h at 36-38 degrees 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 degrees C and 26-28 degrees 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.
D000700:Analgesics / Q000032:analysis*; D002047:Buprenorphine / Q000032:analysis*; D002384:Catalysis; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D009019:Morphinans / Q000032:analysis*; D013797:Thebaine / Q000031:analogs & derivatives
D000700:Analgesics; D009019:Morphinans; D013797:Thebaine; D002047:Buprenorphine; C005283:oripavine