A Chemical Model for the Mechanism of Vitamin K Epoxide Reductase

Article abstract of DOI:10.1021/jo00167a028

The reactions of Vitamin K₁ epoxide and 2,3-dimethylnaphthoquinone epoxide with dithiothreitol and mercaptoethanol have been studied as a potential model for the mechanism of the enzyme vitamin K epoxide reductase.The reaction proceeds with thiol addition to open the oxirane ring, yielding preferentially the 2-thio-3-hydroxy adduct in the case of vitamin K₁ epoxide.Reaction with a second thiol group results in reductive cleavage of this adduct and elimination of water to yield the quinones.All steps are catalyzed by triethylamine.Evidence for a hydroxy-substituted 2,3-dihydronaphthoquinone enolate intermediate in the second step is found in the observation of the corresponding keto compounds as equilibrated side products in the reaction with dithiothreitol.With this reagent, intramolecular reaction to form the cyclic disulfide permits cleavage of the thiol adduct under mild conditions where protonation of the enolate is rapid relative to elimination of the hydroxyl.Isolation and characterization of the intermediates and their conversion to the quinones are described.