Epoxide ring opening reactions are common and important in both biological processes and synthetic applications and can be catalyzed in a non-redox manner by epoxide hydrolases or reductively by oxidoreductases. Here we report that fluostatins (FSTs), a family of atypical angucyclines with a benzofluorene core, can undergo nonenzyme-catalyzed epoxide ring opening reactions in the presence of flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). The 2,3-epoxide ring in FST C is shown to open reductively via a putative enol intermediate, or oxidatively via a peroxylated intermediate with molecular oxygen as the oxidant. These reactions lead to multiple products with different redox states that possess a single hydroxyl group at C-2, a 2,3-vicinal diol, a contracted five-membered A-ring, or an expanded seven-membered A-ring. Similar reactions also take place in both natural products and other organic compounds harboring an epoxide adjacent to a carbonyl group that is conjugated to an aromatic moiety. Our findings extend the repertoire of known flavin chemistry that may provide new and useful tools for organic synthesis.
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De BC, Zhang W, Yang C, Mandi A, Huang C, Zhang L, Liu W, Ruszczycky MW, Zhu Y, Ma M, Bashiri G, Kurtan T, Liu Hw, Zhang C (2022) Flavin-enabled reductive and oxidative epoxide ring opening reactions Nat Commun13: 4896
De BC, Zhang W, Yang C, Mandi A, Huang C, Zhang L, Liu W, Ruszczycky MW, Zhu Y, Ma M, Bashiri G, Kurtan T, Liu Hw, Zhang C (2022) Nat Commun13: 4896
