Department of Chemistry, BioScience Research Collaborative, Rice University, Houston, Texas 77005, United States.
J Am Chem Soc. 2022 Oct 26;144(42):19238-19242. doi: 10.1021/jacs.2c09048. Epub 2022 Oct 12.
The limonoids have attracted significant attention from the synthetic community owing to their striking structural complexity and medicinal potential. Recent efforts notwithstanding, synthetic access to many intact or ring D- limonoids still remains elusive. Here, we report the first synthesis of gedunin, a ring D- limonoid with HSP90 inhibitory activity, that proceeds in 13 steps. Two enabling features in our strategy are the application of modern catalytic transformations to set the key quaternary centers in the carbocyclic core and the use of biocatalytic oxidation at C3 to establish a chemical handle to access the A-ring enone motif. The strategy presented herein may provide an entry point to a wider range of oxidized limonoids.
由于其显著的结构复杂性和药用潜力，柠檬苦素类化合物引起了合成界的极大关注。尽管最近已经做出了努力，但许多完整或环 D-柠檬苦素类化合物的合成方法仍然难以捉摸。在这里，我们报告了具有 HSP90 抑制活性的环 D-柠檬苦素类化合物 gedunin 的首次全合成，总步骤为 13 步。我们策略中的两个关键特点是应用现代催化转化来构建碳环核心中的关键季碳原子，以及在 C3 处使用生物催化氧化来建立一个化学控制来接入 A 环烯酮基序。本文提出的策略可能为更广泛的氧化柠檬苦素类化合物提供了一个切入点。
