Expanding the Reactivity of Flavin-Dependent Halogenases toward Olefins via Enantioselective Intramolecular Haloetherification and Chemoenzymatic Oxidative Rearrangements,ACS Catalysis

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Expanding the Reactivity of Flavin-Dependent Halogenases toward Olefins via Enantioselective Intramolecular Haloetherification and Chemoenzymatic Oxidative Rearrangements
ACS Catalysis ( IF 11.3 ) Pub Date : 2022-10-20 , DOI: 10.1021/acscatal.2c03383
Yuhua Jiang ₁ , Dibyendu Mondal ₁ , Jared C Lewis ₁

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Of the different classes of halogenases characterized to date, flavin dependent halogenases (FDHs) are most associated with site-selective halogenation of electron-rich arenes and enol(ate) moieties in the biosynthesis of halogenated natural products. This capability has made them attractive biocatalysts, and extensive efforts have been devoted to both discovering and engineering these enzymes for different applications. We have established that engineered FDHs can catalyze different enantioselective halogenation processes, including halolactonization of simple alkenes with a tethered carboxylate nucleophile. In this study, we expand the scope of this reaction to include alcohol nucleophiles and a greater diversity of alkene substitution patterns to access a variety of chiral tetrahydrofurans. We also demonstrate that FDHs can be interfaced with ketoreductases to enable halocyclization using ketone substrates in one-pot cascade reactions and that the halocyclization products can undergo subsequent rearrangements to form hydroxylated and halogenated products. Together, these advances expand the utility of FDHs for enantio- and diastereoselective olefin functionalization.

中文翻译：

通过对映选择性分子内卤醚化和化学酶氧化重排扩大黄素依赖性卤化酶对烯烃的反应活性

在迄今为止表征的不同类别的卤化酶中，黄素依赖性卤化酶（FDH）与卤化天然产物生物合成中富电子芳烃和烯醇（酸）部分的位点选择性卤化最相关。这种能力使它们成为有吸引力的生物催化剂，并且人们致力于发现和设计这些酶以用于不同的应用。我们已经确定，工程化的 FDH 可以催化不同的对映选择性卤化过程，包括简单烯烃与束缚的羧酸亲核试剂的卤内酯化。在这项研究中，我们扩大了该反应的范围，包括醇亲核试剂和更多样化的烯烃取代模式，以获得各种手性四氢呋喃。我们还证明，FDH 可以与酮还原酶连接，在一锅级联反应中使用酮底物进行卤环化，并且卤环化产物可以进行后续重排，形成羟基化和卤化产物。总之，这些进步扩大了 FDH 在对映和非对映选择性烯烃官能化方面的效用。

更新日期：2022-10-20

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