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Asymmetric abstraction of two chemically-equivalent methylene hydrogens: significant enantioselectivity of endoperoxide presented by fumitremorgin B endoperoxidase†
Physical Chemistry Chemical Physics ( IF 2.9 ) Pub Date : 2018-10-02 00:00:00 , DOI: 10.1039/c8cp05637d Jian-Nan Ji 1, 2, 3, 4, 5 , Shi-Lu Chen 1, 2, 3, 4, 5
Physical Chemistry Chemical Physics ( IF 2.9 ) Pub Date : 2018-10-02 00:00:00 , DOI: 10.1039/c8cp05637d Jian-Nan Ji 1, 2, 3, 4, 5 , Shi-Lu Chen 1, 2, 3, 4, 5
Affiliation
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The combination of the inert C–H bond activation and asymmetric synthesis, especially the transformation of prochiral sp3 precursors to chiral sp3 centers, is a profound challenge. In the present DFT calculations, the unique enantioselectivity in verruculogen biosynthesis catalyzed by fumitremorgin B endoperoxidase (FtmOx1) has been mechanistically investigated, where a prochiral methylene in fumitremorgin B is dominantly converted to an R-chiral eight-membered endoperoxy ring. FtmOx1 is the first-reported mononuclear α-ketoglutarate-dependent non-heme iron enzyme responsible for chiral endoperoxide formation, which handles the substrate using a Tyr224 radical resulting from the hydrogen abstraction by an FeIV![[double bond, length as m-dash]](https://www.rsc.org/images/entities/char_e001.gif)
O species. It is demonstrated that the perfect enantioselectivity of the R-endoperoxy ring originates from the asymmetric abstraction of two chemically-equivalent methylene hydrogens from substrate chain A by the Tyr224 radical and the high conformation stability of the resultant chain A radical due to steric effects. The barrier difference in the abstraction of two hydrogens is 5.6 kcal mol−1. The hydrogen abstraction by the Tyr224 radical is rate-limiting in the FtmOx1 reaction with an overall barrier of 18.6 kcal mol−1. The results obtained here advance the understanding of the chemistry in enantioselectivity, providing a potentially general way for the transformation of prochiral sp3 precursors to chiral sp3 centers.
中文翻译：
两个化学等价的亚甲基氢的不对称抽象：富莫莫菌素B内过氧化物酶†呈现的内过氧化物显着对映选择性†
惰性C–H键活化和不对称合成的结合，尤其是前手性sp 3前体向手性sp 3中心的转化，是一个巨大的挑战。在目前的DFT计算中，已通过机械方法研究了fumitremorgin B内过氧化物酶（FtmOx1）催化的疣蛋白原生物合成中的独特对映选择性，其中fumitremorgin B中的前手性亚甲基主要转化为R-手性八元内过氧化物环。FtmOx1是负责手性内过氧化物形成的第一个报告的依赖单核α-酮戊二酸的非血红素铁依赖性酶，其使用由Fe IV夺氢而产生的Tyr224自由基处理底物O种。证明了R-内过氧基的完美对映选择性源于Tyr224基团从底物链A上不对称地提取两个化学等价的亚甲基氢，以及由于空间效应而导致的链A基团的高构象稳定性。两个氢的抽象中的势垒差为5.6 kcal mol -1。在FtmOx1反应中，Tyr224自由基对氢的吸收是限速的，总势垒为18.6 kcal mol -1。此处获得的结果促进了对映体化学的理解，为前手性sp 3前体向手性sp 3的转化提供了潜在的通用方法。 中心。
更新日期：2018-10-02
O species. It is demonstrated that the perfect enantioselectivity of the R-endoperoxy ring originates from the asymmetric abstraction of two chemically-equivalent methylene hydrogens from substrate chain A by the Tyr224 radical and the high conformation stability of the resultant chain A radical due to steric effects. The barrier difference in the abstraction of two hydrogens is 5.6 kcal mol−1. The hydrogen abstraction by the Tyr224 radical is rate-limiting in the FtmOx1 reaction with an overall barrier of 18.6 kcal mol−1. The results obtained here advance the understanding of the chemistry in enantioselectivity, providing a potentially general way for the transformation of prochiral sp3 precursors to chiral sp3 centers.
中文翻译：
两个化学等价的亚甲基氢的不对称抽象：富莫莫菌素B内过氧化物酶†呈现的内过氧化物显着对映选择性†
惰性C–H键活化和不对称合成的结合，尤其是前手性sp 3前体向手性sp 3中心的转化，是一个巨大的挑战。在目前的DFT计算中，已通过机械方法研究了fumitremorgin B内过氧化物酶（FtmOx1）催化的疣蛋白原生物合成中的独特对映选择性，其中fumitremorgin B中的前手性亚甲基主要转化为R-手性八元内过氧化物环。FtmOx1是负责手性内过氧化物形成的第一个报告的依赖单核α-酮戊二酸的非血红素铁依赖性酶，其使用由Fe IV夺氢而产生的Tyr224自由基处理底物
O种。证明了R-内过氧基的完美对映选择性源于Tyr224基团从底物链A上不对称地提取两个化学等价的亚甲基氢，以及由于空间效应而导致的链A基团的高构象稳定性。两个氢的抽象中的势垒差为5.6 kcal mol -1。在FtmOx1反应中，Tyr224自由基对氢的吸收是限速的，总势垒为18.6 kcal mol -1。此处获得的结果促进了对映体化学的理解，为前手性sp 3前体向手性sp 3的转化提供了潜在的通用方法。 中心。
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