Department of Chemistry, University of California, Davis, One Shields Ave., Davis, CA 95161, USA.
Angew Chem Int Ed Engl. 2022 Jun 20;61(25):e202203072. doi: 10.1002/anie.202203072. Epub 2022 Apr 25.
Panowamycins are a group of isochroman-based natural products first isolated from Streptomyces sp. K07-0010 in 2012 by Satoshi Ōmura and co-workers that exhibit modest anti-trypanosomal activity. Herein we demonstrate the first syntheses of these natural products and their epimers. Stereoselective dirhodium-catalyzed C-H insertion reactions with a donor/donor carbene construct the substituted isochroman core in the key bond-forming step. The syntheses are completed without the use of protecting groups and feature a late-stage Wacker oxidation. Incongruent NMR spectra between natural and synthetic samples revealed the structural misassignment of panowamycin A and veramycin F. Computational NMR studies suggested panowamycin A to be an alternate diastereomer, which was confirmed by synthesizing this isomer. Concurrent with this work, in 2021 Mahmud and co-workers came to the same conclusion with an updated NMR analysis of panowamycin A. In a divergent, asymmetric sequence, we report the synthesis of panowamycin A, panowamycin B, TM-135, and veramycin F.
盘诺霉素是一类异苯并呋喃为基本结构的天然产物，于 2012 年由 Satoshi Ōmura 及其同事首次从链霉菌属 K07-0010 中分离得到，具有中等抗锥虫活性。本文首次对这些天然产物及其差向异构体进行了全合成。手性双钌催化的供体/供体卡宾 C-H 插入反应是构建关键键形成步骤中取代异苯并呋喃核心的立体选择性步骤。该合成过程无需使用保护基团，并且具有后期的瓦克氧化反应。天然产物和合成产物之间不一致的 NMR 谱表明盘诺霉素 A 和威拉霉素 F 的结构错误归属。计算 NMR 研究表明盘诺霉素 A 是另一种非对映异构体，通过合成这种异构体得到了证实。与这项工作同时进行的是，2021 年 Mahmud 及其同事通过对盘诺霉素 A 的更新 NMR 分析得出了相同的结论。在一个发散的、不对称的序列中，我们报告了盘诺霉素 A、盘诺霉素 B、TM-135 和威拉霉素 F 的合成。
