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Published on: April 19, 2019
Unlocking mild-condition benzene ring contraction using nonheme diiron N-oxygenase
Yuan-Yang Guo1, Ze-Hua Tian1, ChunHua Ma1
1State Key Laboratory of Antiviral Drugs, Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, NMPA Key Laboratory for Research and Evaluation of Innovative Drug, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University Xinxiang Henan 453007 China guoyuanyang@163.com.
Abstract:
Benzene ring contractions are useful yet rare reactions that offer a convenient synthetic route to various valuable chemicals. However, the traditional methods of benzene contraction rely on noble-metal catalysts under extreme conditions with poor efficiency and uncontrollable selectivity. Mild-condition contractions of the benzene ring are rarely reported. This study presents a one-step, one-pot benzene ring contraction reaction mediated by an engineered nonheme diiron N-oxygenase. Using various aniline substrates as amine sources, the enzyme causes the phloroglucinol-benzene-ring contraction to afford a series of 4-cyclopentene-1,3-dione structures. A reaction detail study reveals that the nonheme diiron N-oxygenase first oxidizes the aromatic amine to a nitroso intermediate, which then attacks the phloroglucinol anion and causes benzene ring contraction. Besides, we have identified two potent antitumor compounds from the ring-contracted products.
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