Oxygenation Reaction of Methyl Valproate with A Mono-oxygenase Model Reagent : Implication for Stereochemical Identification of the Mammalian Metabolites of Valproic Acid

Abstract

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 β-lactone 6a, γ-lectone 7a and 7b prepared from the oxygenation products. The asymmetric synthesis of (+)-7a was also achieved.