Allylic hydroxylation of cyclohexene.

Details

• Personal Author:
  Leibman KC ; Ortiz E
• Description:
  Drugs containing cyclohexene (110838) rings (hexobarbital (56291), thiocarbanidin (92977)) are metabolically hydroxylated at the allyl position. This reaction was studied with cyclohexene (CH). Microsomes or 9000 g supernatant fractions of rats or rabbits catalyzed the conversion of CH to 2-cyclohexen-1-o1 in the presence of a reduced nicotinamide-adenine-dinucleotide-phosphate generating system; the latter could not be substituted by a reduced nicotinamide-adenine-dinucleotide generating system. Allylic hydroxylation was stimulated by magnesium ions. The product was identified by gas-liquid chromatography, direct and after formation of the trimethylsilyl-derivative, and by mass spectrometry. The reaction was induced over five-fold by phenobarbital (PB) treatment of rats. CH oxide was formed at a fraction of the rate of 2-CH-1-o1 in control preparations, but to a greater extent than the alcohol in preparations from PB treated rats. Cyclohexane-diol formation was also induced by PB. The formation of a small amount of 2-cyclohexen- 1-one could be detected in preparations from PB treated rats. SKF 525-A was a more potent inhibitor of allylic hydroxylation than was metyrapone, but both inhibitors caused greater inhibition of epoxidation than of hydroxylation. 2-CH-1-o1 or 1-one were not formed from CH oxide in-vitro. After feeding CH to rats, 2-CH-1-one was found in urine; no 2-CH-1-o1 was detected before or after hydrolysis with beta-glucuronidase. [Description provided by NIOSH]
• Subjects:
  Chemistry Energy Metabolism Hydrocarbons Occupational Health Safety Solvents
• Keywords:
  NIOSH-Publication; Grants-other; Hydrocarbons; Organic-solvents; Hydroxylation-reactions; Chemical-reactions; Drugs-interactions; Metabolism
• ISSN:
  0014-9446
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Florida ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  36
• NIOSHTIC Number:
  nn:00071494
• Citation:
  Fed Proc 1976 Jan; 36:666
• Contact Point Address:
  Pharmacology and Therapeutics Univ of Florida Coll of Med Dept of Pharma & Therapeutics Gainesville, Fla 32601
• CAS Registry Number:
  (±)-Hexobarbital (CAS RN 56-29-1) ; Cyclohexene (CAS RN 110-83-8) ; Thiourea, N-[4-(2-methylpropoxy)phenyl]-N′-[4-(2-pyridinyl)phenyl]- (CAS RN 92-97-7)
• Federal Fiscal Year:
  1976
• NORA Priority Area:
  Other Occupational Concerns ; Grants Other
• Performing Organization:
  University of Florida Gainesville, Gainesville, Florida
• Peer Reviewed:
  False
• Start Date:
  19710101
• Source Full Name:
  Federation Proceedings
• End Date:
  19841130
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/247422/cdc_247422_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]