Dynamically Complex [6+4] and [4+2] Cycloadditions in the Biosynthesis of Spinosyn A
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- 作者：Ashay Patel ; Zhuo Chen ; Zhongyue Yang ; Osvaldo Gutiérrez ; Hung-wen Liu ; K. N. Houk ; Daniel A. Singleton
- 刊名：Journal of the American Chemical Society
- 出版年：2016
- 出版时间：March 23, 2016
- 年：2016
- 卷：138
- 期：11
- 页码：3631-3634
- 全文大小：303K
- ISSN：1520-5126
文摘
SpnF, an enzyme involved in the biosynthesis of spinosyn A, catalyzes a transannular Diels–Alder reaction. Quantum mechanical computations and dynamic simulations now show that this cycloaddition is not well described as either a concerted or stepwise process, and dynamical effects influence the identity and timing of bond formation. The transition state for the reaction is ambimodal and leads directly to both the observed Diels–Alder and an unobserved [6+4] cycloadduct. The potential energy surface bifurcates and the cycloadditions occur by dynamically stepwise modes featuring an “entropic intermediate”. A rapid Cope rearrangement converts the [6+4] adduct into the observed [4+2] adduct. Control of nonstatistical dynamical effects may serve as another way by which enzymes control reactions.