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Metabolism of 1,1,1,2,2‐pentafluorohexane and 1,1‐difluorocyclohexane by rat liver microsomes in vitro
Author(s) -
Baker Michael H.,
Foster Allan B.,
Hegedus Lajos,
Jarman Michael,
Rowlands Martin G.,
Coe Paul L.,
Troth J.
Publication year - 1984
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200111005
Subject(s) - hydroxylation , microsome , chemistry , metabolite , metabolism , in vitro , phenobarbital , mass spectrometry , halogenation , medicinal chemistry , stereochemistry , organic chemistry , biochemistry , chromatography , enzyme , pharmacology , biology
Metabolism of 1,1,1,2,2‐pentafluorohexane with liver microsomes from phenobarbital‐treated rats gave only one metabolite, namely, the 5‐hydroxy derivative. Under similar conditions 1,1‐difluorocyclohexane was metabolized to give mainly the 3‐ and 4‐hydroxy derivatives in the ratio 1:∼5.5 The structures of these metabolites were established by chemical ionization (CI) and/or electron impact (EI) mass spectrometry and confirmed by synthesis in the case of 1,1‐difluorocyclohexan‐4‐ol. Oxidation of 1,1‐difluorocyclohexane with lead tetrakis(trifluoroacetate) also gave, inter alia , the 3‐ and 4‐hydroxy derivatives. In saturated hydrocarbons complete replacement of hydrogen by fluorine at one particular carbon will not only block microsomal hydroxylation thereat but will also inhibit hydroxylation at neighbouring hydrogen‐bearing carbons, (α almost completely, β markedly, γ slightly).