Oxygenation reaction of methyl valproate with a mono-oxygenase model reagent: implication for stereochemical identification of the mammalian metabolites of valproic acid.
Non-enzymic oxygenation reaction of methyl valproate (2) utilizing a simple model system for mono-oxygenases, Fe(MeCN)2(6+)-H2O2-Ac2O in MeCN, was investigated in connection with stereochemical analyses of the mammalian metabolites of 1. This oxygenation reaction of methyl valproate (2) gave a 92:8 mixture of the anti-isomer 4a and the syn-isomer 4b, together with 5a, and 5b corresponding to the mammalian metabolites of 1. The stereochemistry of 4a, 5a, and 5b was elucidated by spectral analyses of the corresponding beta-lactone 6a, gamma-lactone 7a and 7b prepared from the oxygenation products. The asymmetric synthesis of (+)-7a was also achieved.
Kotani
E
E
Showa College of Pharmaceutical Sciences, Tokyo Japan.
Takeya
T
T
Yoshiike
M
M
Watanabe
A
A
Tobinaga
S
S
D000818:Animals; D005296:Ferrous Compounds / Q000737:chemistry* / Q000378:metabolism; D007202:Indicators and Reagents / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D008745:Methylation; D008956:Models, Chemical; D010084:Oxidation-Reduction; D051381:Rats; D013237:Stereoisomerism; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000378:metabolism*
D005296:Ferrous Compounds; D007202:Indicators and Reagents; D014635:Valproic Acid