Concise Chemoenzymatic Synthesis of Gedunin
Concise Chemoenzymatic Synthesis of Gedunin
复制标题
葛杜宁的简明化学酶法合成
DOI：
10.1021/jacs.2c09048
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发表时间：
2022
影响因子：
15
通讯作者：
Renata, Hans
中科院分区：
文献类型：
--
作者：
Li, Jian;Chen, Fang;Renata, Hans
柠檬苦素类化合物由于其惊人的结构复杂性和药用潜力而引起了合成界的极大关注。尽管最近做出了努力，但合成获得许多完整或环状 D-仲柠檬酸仍然难以实现。在这里，我们报告了 gedunin 的首次从头合成，gedunin 是一种具有 HSP90 抑制活性的环 D-仲柠檬酸，分 13 个步骤进行。我们策略中的两个有利特征是应用现代催化转化在碳环核心中设置关键的四级中心，以及在 C3 上使用生物催化氧化来建立化学手柄来访问 A 环烯酮基序。本文提出的策略可以为更广泛的氧化柠檬苦素提供切入点。
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-secolimonoids still remains elusive. Here, we report the firstde novosynthesis of gedunin, a ring D-secolimonoid 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.