Cyclic 1,2-diketones as core building blocks: a strategy for the total synthesis of (-)-terpestacin.
Cyclic 1,2-diketones as core building blocks: a strategy for the total synthesis of (-)-terpestacin.
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DOI：
10.1002/chem.200903356
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发表时间：
2010-06-01
影响因子：
4.3
通讯作者：
Vance, Jennifer A.
中科院分区：
文献类型：
--
作者：
Trost, Barry M.;Dong, Guangbin;Vance, Jennifer A.
我们报告了我们在全合成 (−)-terpestacin (1) 方面所做的工作的完整说明，(−)-terpestacin (1) 是一种最初从真菌菌株 Arthrinium sp 中分离出来的二倍半萜烯。 FA1744。 terpestacin 具有良好的抗 HIV/抗癌活性以及新颖的结构，使其成为有吸引力的合成靶点。开发了一种基于环状 1,2-二酮（双酚）独特反应性的策略，并从市售的 3-甲基-1,2-环戊二酮中以最长的线性序列通过 20 个步骤实现了 1 的全合成 (19)。我们合成的关键特征是双重使用“Pd AAA-Claisen”协议，首先在早期阶段生成C1四元中心，然后在后期阶段安装侧链。此外，还合成了一个相当不寻常的 ene-1,2-二酮部分，并将其用作优异的迈克尔受体以连接 C15 取代基。已经检查并仔细评估了几种可能的全合成路线。在我们的探索过程中，还解决了许多有趣的化学选择性问题，例如高选择性闭环复分解（RCM）以及在三个三取代烯烃存在下对二取代烯烃进行具有挑战性的氧化。
We report a full account of our work towards the total synthesis of (−)-terpestacin (1), a sesterterpene originally isolated from fungal strain Arthrinium sp. FA1744. Its promising anti-HIV/anti-cancer activity as well as its novel structure make terpestacin an attractive synthetic target. A strategy based on the unique reactivity of cyclic 1,2-diketones (diosphenol) was developed, and total synthesis of 1 was achieved in 20 steps in the longest linear sequence from commercially available 3-methyl-1,2-cyclopentanedione (19). The key feature of our synthesis is represented by double usage of a “Pd AAA-Claisen” protocol, first in the early stage to generate the C1 quaternary center and second in the late stage to install the side chain. In addition, a rather unusual ene-1,2-dione moiety was synthesized and utilized as an excellent Michael acceptor to attach the C15 substituent. Several possible routes towards the total synthesis have been examined and carefully evaluated. During our exploration, many interesting chemoselectivity issues have also been addressed, such as a highly selective ring-closing metathesis (RCM) and a challenging oxidation of a disubstituted olefin in the presence of three trisubstiuted ones.
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