Metabolism of tetramethrin isomers in rat. III. Stereochemistry of reduced metabolites.
1. Three main urinary metabolites, two isomers of 3-hydroxycyclohexane-1,2-dicarboximide (3-OH-HPI-1 and 2) and 1,2-tetrahydrodicarboxylic acid (TCDA) were purified from rat treated with (1RS, trans)-tetramethrin [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate]. 2. To elucidate the mechanism of formation of these reduced metabolites, the stereochemistry of 3-OH-HPI-1, 3-OH-HPI-2 and TCDA was clarified by chemical reactions, spectroanalysis (nmr) and X-ray analysis. 3. The sole difference in configuration between 3-OH-HPI-1 and 3-OH-HPI-2 was found to be the orientation of the hydroxyl group to the cyclohexane ring, and both of these reduced metabolites showed cis-addition of two hydrogens. In contrast, reduction resulted in the trans form with TCDA. 4. These findings indicate the existence of two different reduction reaction mechanisms in the rat.
Tomigahara
Y
Y
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd, Osaka, Japan.
Onogi
M
M
Miki
M
M
Yanagi
K
K
Shiba
K
K
Kaneko
H
H
Nakatsuka
I
I
Yamada
H
H
D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006900:Hydroxylation; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D011722:Pyrethrins / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014961:X-Ray Diffraction
D011722:Pyrethrins; C009424:tetramethrin