Unlocking mild-condition benzene ring contraction using nonheme diiron N-oxygenase

• Published in: Chemical science (Cambridge) Vol. 14; no. 42; pp. 11907 - 11913
• Main Authors: Guo, Yuan-Yang, Tian, Ze-Hua, Ma, Chunhua, Han, Yu-Chen, Bai, Dachang, Jiang, Zhiyong
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.11.2023; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Aniline; Benzene; Chemistry; Chemistry, Multidisciplinary; Cyclopentene; Noble metals; Phloroglucinol; Physical Sciences; Science & Technology; Substrates; RADICAL CHEMISTRY; IN-VITRO; THERMAL REARRANGEMENTS; CARBENES; CROCONAMIDES; REACTIVITY; CLEAVAGE; AROMATIC-COMPOUNDS
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d3sc04660e

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.