Evolution of a Unified Strategy for Complex Sesterterpenoids: Progress toward Astellatol and the Total Synthesis of (-)-Nitidasin.
Evolution of a Unified Strategy for Complex Sesterterpenoids: Progress toward Astellatol and the Total Synthesis of (-)-Nitidasin.
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DOI：
10.1002/chem.201501423
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发表时间：
2015-09-21
期刊：
影响因子：
--
通讯作者：
Trauner D
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文献类型：
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作者：
Hog DT;Huber FM;Jiménez-Osés G;Mayer P;Houk KN;Trauner D
Astellatol和nitidasin属于二萜类化合物的子集，其共享具有异丙基取代基的空间阻碍的反式-二氢茚基序。此外，这些天然产物具有有趣的多环系统，为化学合成带来了重大挑战。在此，我们详细介绍了我们的异丙基反式-氢化茚二萜类化合物的立体选择性策略的演变。我们的努力包括几个积木的合成，使研究对所有分子的这种萜类，和先进的中间体，我们最初的路线走向仿生合成astellatol。这些发现为第二代和第三代astellatol方法提供了基础，最终最终实现了（−）-nitidasin的对映选择性全合成。特别是，我们精心策划了一系列底物控制的转化，以安装目标分子的十个立体中心，并以收敛的方式锻造碳环骨架。此外，我们披露了我们的进展，对合成的astellatol和提供见解，一些观察到的，但意想不到的非对映选择性详细的量子力学计算。
Astellatol and nitidasin belong to a subset of sesterterpenoids that share a sterically encumbered trans-hydrindane motif with an isopropyl substituent. In addition, these natural products feature intriguing polycyclic ring systems posing significant challenges for chemical synthesis. Herein, we detail the evolution of our stereoselective strategy for isopropyl trans-hydrindane sesterterpenoids. Our endeavors included the synthesis of several building blocks, enabling studies toward all molecules of this terpenoid subclass, and of advanced intermediates of our initial route toward a biomimetic synthesis of astellatol. These findings provided the basis for a second-generation and a third-generation approach toward astellatol that eventually culminated in the enantioselective total synthesis of (−)-nitidasin. In particular, we orchestrated a series of substrate-controlled transformations to install the ten stereogenic centers of the target molecule and forged the carbocyclic backbone in a convergent fashion. Furthermore, we disclose our progress toward the synthesis of astellatol and provide insights into some observed yet unexpected diastereoselectivities by detailed quantum-mechanical calculations.