Department of Chemistry and Biochemistry, ‡Department of Chemical and Biomolecular Engineering, University of California , Los Angeles, California 90095, United States.
J Am Chem Soc. 2015 Oct 28;137(42):13518-23. doi: 10.1021/jacs.5b06656. Epub 2015 Oct 15.
The transannular [6 + 4] cycloaddition proposed as a step in the biosynthesis of heronamide A has been modeled using density functional theory. The proposed cycloaddition is highly stereoselective, affording a single product. The reaction proceeds through an ambimodal transition state that directly leads to a [4 + 2] adduct in addition to the observed [6 + 4] adduct. Interconversion of these adducts is possible via a facile Cope rearrangement. The [6 + 4] adduct is thermodynamically more stable than the [4 + 2] adduct by 5.2 kcal mol(-1) due to a combination of the ring and steric strain in the [4 + 2] product. The results strongly support the plausibility of the proposed transannular [6 + 4] cycloaddition in the biogenesis of heronamide A and may provide insights to designing substrates that selectively undergo [6 + 4] cycloaddition to form unbridged 10-membered rings.
提议的作为海洛纳密胺 A 生物合成步骤的中环 [6+4] 环加成已使用密度泛函理论进行建模。所提议的环加成具有高度的立体选择性，仅提供单一产物。反应通过双模态过渡态进行，直接导致 [4+2] 加合物以及观察到的 [6+4] 加合物。这些加合物可以通过容易的 Cope 重排相互转化。[6+4] 加合物由于 [4+2] 产物中环和空间应变的组合，比 [4+2] 加合物热力学上稳定 5.2 kcal mol(-1)。结果强烈支持提议的中环 [6+4] 环加成在海洛纳密胺 A 生物合成中的合理性，并可能为设计选择性经历 [6+4] 环加成以形成无桥 10 元环的底物提供见解。
