Key Laboratory of Tropical Marine Bioresources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China.
University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China.
Nat Commun. 2022 Aug 20;13(1):4896. doi: 10.1038/s41467-022-32641-1.
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.
环氧化物开环反应在生物过程和合成应用中都很常见且重要，可通过环氧化物水解酶以非氧化还原方式，或通过氧化还原酶进行还原催化。在此我们报告称，氟伐他汀（FST）是一类具有苯并菲核心的非典型蒽环类抗生素，可在黄素腺嘌呤二核苷酸（FAD）和烟酰胺腺嘌呤二核苷酸（NADH）存在下进行非酶催化的环氧化物开环反应。FST C 的 2,3-环氧环被证明可通过假定的烯醇中间体进行还原开环，或通过过氧中间体与分子氧进行氧化开环，其中分子氧为氧化剂。这些反应生成了多种具有不同氧化还原态的产物，它们在 C-2 位具有一个羟基、一个 2,3-顺式二醇、一个缩合的五元 A 环或一个扩展的七元 A 环。类似的反应也发生在含有与芳香部分共轭的羰基相邻的环氧基团的天然产物和其他有机化合物中。我们的发现扩展了已知黄素化学的范围，这可能为有机合成提供新的有用工具。
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