Computational Exploration of the Mechanism of Critical Steps in the Biomimetic Synthesis of Preuisolactone A, and Discovery of New Ambimodal (5 + 2)/(4 + 2) Cycloadditions.
Computational Exploration of the Mechanism of Critical Steps in the Biomimetic Synthesis of Preuisolactone A, and Discovery of New Ambimodal (5 + 2)/(4 + 2) Cycloadditions.
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DOI：
10.1021/jacs.1c01856
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发表时间：
2021-04
影响因子：
15
通讯作者：
Hong Zhang;Alexander J. E. Novak;Cooper S. Jamieson;Xiao-song Xue;Shuming Chen;D. Trauner;K. Houk
中科院分区：
文献类型：
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作者：
Hong Zhang;Alexander J. E. Novak;Cooper S. Jamieson;Xiao-song Xue;Shuming Chen;D. Trauner;K. Houk
用ωB97X-D密度泛函理论对特劳纳仿生合成前优索内酯A的各个步骤的机理进行了计算研究，详细阐述和完善了几个独特过程的机理。邻苯二酚与羟基邻苯二酚的环加成反应为双峰过渡态，生成(5+2)(H移位)和(4+2)环加成产物，原则上可通过α-酮醇重排相互转化。用分子动力学模拟对这种双峰环加成反应的介电选择性的起源进行了计算研究，并通过实验进行了进一步的验证。在碳酸氢根存在下，去质子化的羟基邻苯二酚只生成(5+2)环加成产物。提出了苯甲酸重排导致环收缩的新机理。
Computational studies with ωB97X-D density functional theory of the mechanisms of the steps in Trauner's biomimetic synthesis of preuisolactone A have elaborated and refined mechanisms of several unique processes. An ambimodal transition state has been identified for the cycloaddition between an o-quinone and a hydroxy-o-quinone; this leads to both (5 + 2) (with H shift) and (4 + 2) cycloaddition products, which can in principle interconvert via α-ketol rearrangements. The origins of periselectivity of this ambimodal cycloaddition have been investigated computationally with molecular dynamics simulations and tested further by an experimental study. In the presence of bicarbonate ions, the deprotonated hydroxy-o-quinone leads to only the (5 + 2) cycloaddition adduct. A new mechanism for a benzilic acid rearrangement resulting in ring contraction is proposed.