Department of Chemistry , Yale University , 225 Prospect Street , New Haven , Connecticut 06520-8107 , United States.
J Am Chem Soc. 2019 Jan 30;141(4):1479-1483. doi: 10.1021/jacs.8b13127. Epub 2019 Jan 14.
We report the total syntheses of two indole diterpenoid natural products, paspaline A and emindole PB. Paspaline A is synthesized in a 9-step sequence from commercially available materials. The first total synthesis of emindole PB is accomplished in 13 steps and confirms a previously ambiguous structural assignment. Density functional theory calculations are utilized to interrogate the key carbocationic rearrangement in a predictive capacity to aid in the selection of the most favorable precursor substrate. This work highlights how retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.
我们报告了两种吲哚二萜天然产物帕斯卡林 A 和 emindole PB 的全合成。Paspaline A 是从商业可得的材料通过 9 步序列合成的。emindole PB 的首次全合成通过 13 步完成，并证实了以前不确定的结构分配。密度泛函理论计算被用于以预测能力来探究关键的碳正离子重排，以帮助选择最有利的前体底物。这项工作强调了如何通过量子化学计算来增强反合成设计，以揭示能量可行的合成断键，从而最大限度地减少耗时和昂贵的经验评估。
