Mechanistic Study of 2-methyl-1,4-naphthoquinone (Vitamin K3) Derivatives and Their Reactivity towards Thiols and Amines


Erica Wenker

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Various biological activities in the human body are ascribed to 1,4-naphthoquinones. For instance, 2-methyl-1,4-naphthoquinone (vitamin K3) has been shown to have anti-cancerous properties through the reaction with the cysteine residue in tyrosine phosphatase. Therefore it is interesting to study the reactivity of 1,4-naphthoquinones with nucleophiles such as amines and thiols representing the cysteine residue in the active site of tyrosine phosphatase. One aspect of the biological activity could be caused by the acidic nature of the a-hydrogen of the methyl group. Here we study the acidity of the methyl group of 2-bromo-3-methyl-1,4-naphthoquinone, 2-chloro-3-methyl-1,4-naphthoquinone, 2-ethylthio-3-methyl-1,4-naphthoquinone and 2-methyl-3-vinyl-1,4-naphthoquinone. The H-D exchange of the a-hydrogen of these 1,4-naphthoquinones is investigated in methanol-D in the presence of triethylamine. Our study suggests the a-hydrogen of the bromo derivative to be most acidic, followed by the a-hydrogen of the chloro and the ethylthio derivatives. Due to the acidic nature of the methyl group, 2-halogeno-3-methyl-1,4-naphthoquinones readily react with alkylamines at the methyl group. In this study 2-bromo-3-methyl-1,4-naphthoquinone is being compared with 2-chloro-3-methyl-1,4-naphthoquinone in reactions with methylamine, ethylamine, isopropylamine and tert -butylamine. These reactions show a clear difference in reactivity between the bromo derivative and the chloro derivative. In the reaction with ethylamine, 2-methyl-3-vinyl-1,4-naphthoquinone gave no clear products, but in its reaction with ethanethiolate, at least three addition products at the vinyl group are identified.


Tetsuo Otsuki




Howard Hughes Medical Institute Undergraduate Science Education Grant

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