Program on Chemical Sciences, Chulabhorn Graduate Institute, Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, 906 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand.
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Laksi, Bangkok 10210, Thailand.
Org Lett. 2022 Jun 24;24(24):4470-4473. doi: 10.1021/acs.orglett.2c01760. Epub 2022 Jun 14.
Herein, we report the first total synthesis of pentaketide ansamycin microansamycin H. Key to our success was the -selective epoxide-opening -alkylation to construct the elusive seven-membered benzoxepane core. Due to the electron-rich disposition of the aromatic substrate, our pivotal transformation was hindered by competing electrophilic aromatic substitution at multiple -based nucleophilic sites that generated kinetically favored products. Judicious choices of transition metal Lewis acid promoters biased toward the formation of the desired oxepane.
在此，我们报告 pentaketide ansamycin 微ansamycin H 的首次全合成。我们成功的关键是 -选择性环氧化物开环 -烷基化，以构建难以捉摸的七元苯并[g]氧杂环庚烷核心。由于芳香底物的富电子排布，我们的关键转化受到多个基于 -的亲核位点的竞争亲电芳香取代的阻碍，这些亲核位点生成了动力学上有利的产物。过渡金属路易斯酸促进剂的明智选择有利于形成所需的氧杂环庚烷。
