Metabolism of the insecticidally active GABA sub A receptor antagonist 4-sec-(3,4- sup 3 H sub 2 )butyl-1-(4-cyanophenyl)-2,6,7-trioxabicyclo(2. 2. 2)octane

Journal Article · Wed Feb 28 23:00:00 EST 1990 · Journal of Agricultural and Food Chemistry; (USA)

DOI:https://doi.org/10.1021/jf00093a055· OSTI ID:6524621

Deng, Yanli; Palmer, C J; Toia, R F; Casida, J E ^[1]

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1. Univ. of California, Berkeley (USA)

4-sec-(3,4-{sup 3}H{sub 2})Butyl-1-(4-cyanophenyl)-2,6,7-trioxabicyclo(2.2.2)octane (referred to as ({sup 3}H)COB) was examined as an example of a new class of insecticidally active compounds that block the {gamma}-aminobutyric acid gated chloride channel. Metabolites were identified by thin-layer cochromatography with standards from synthesis and by consideration of their hydrolytic and oxidative degradation products formed in situ on two-dimensional silica gel chromatoplates. Metabolism of ({sup 3}H)COB by mouse liver and housefly abdomen microsomes is dependent on fortification with NADPH. The O-methylene and sec-butyl sites are sensitive to oxidation. Each carbon of the sec-butyl group is individually functionalized with strong preference for the methylene site in the mouse but not the housefly microsomal system. O-Methylene hydroxylation initiates spontaneous cage opening to form an aldehyde that undergoes metabolic reduction, ultimately yielding the same cyanobenzoate ester of 2,2-bis-(hydroxymethyl)-3-methylpentan-1-ol formed by direct hydrolysis. Houseflies injected with ({sup 3}H)COB form many if not all of the same metabolites, with major products being the aforementioned cyanobenzoate, the orthoester oxidized at the sec-butyl methylene site, and polar conjugates.

• OSTI ID: 6524621
• Journal Information: Journal of Agricultural and Food Chemistry; (USA), Journal Name: Journal of Agricultural and Food Chemistry; (USA) Vol. 38:3; ISSN 0021-8561; ISSN JAFCA
• Country of Publication: United States
• Language: English

Related Subjects

553003* -- Agriculture & Food Technology-- Pest & Disease Control-- (1987-)
60 APPLIED LIFE SCIENCES
ANIMALS
ARTHROPODS
BODY
CELL CONSTITUENTS
DIGESTIVE SYSTEM
GLANDS
HYDROGEN COMPOUNDS
INSECTICIDES
INSECTS
INVERTEBRATES
ISOTOPE APPLICATIONS
LIVER
MAMMALS
METABOLISM
METABOLITES
MICE
MICROSOMES
ORGANOIDS
ORGANS
PESTICIDES
RIBOSOMES
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES