Enantioselective Total Synthesis of the Diterpenes Kempene-2, Kempene-1, and 3-epi-Kempene-1 from the Defense Secretion of Higher Termites
Enantioselective Total Synthesis of the Diterpenes Kempene-2, Kempene-1, and 3-epi-Kempene-1 from the Defense Secretion of Higher Termites
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DOI：
10.1002/anie.201007551
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Metz, Peter
中科院分区：
文献类型：
--
作者：
Schubert, Melanie;Metz, Peter
白蚁亚科Nasutitermitinae的士兵在世界各地发现保护自己免受侵略者通过喷射含有结构独特的四环二萜的分泌物。[1]Kempene-2（1）、kempene-1（2）和3-epi-kempene-1（3）是具有kempane骨架的二萜，其首先从种类Nasutitermes kemanensis [2]和Bulbitermes singaporensis [3]的白蚁士兵的防御分泌物中分离（方案1）。[4，5]这些特殊的天然产物的合成已被证明是有问题的。到目前为止，只有外消旋的kempene-2（rac-1）的全合成被报道[6]，而许多其他的合成研究[7]还没有导致所需的kempane。近年来，我们成功地合成了4-去甲基-3 α-羟基-15-rippertene（5），该化合物与rippertene 4相似，是从Nasutitermes rippertii和Nasutitermes ephratae中分离得到的，分子内Diels-Alder反应是合成的关键。[8]最近对5的生物活性的研究[9]表明，这种去甲二萜对B表现出抗生素活性。枯草芽孢杆菌类似于抗微生物trinervitanes。[10]在我们通过多米诺复分解反应[12，1 - 3]构建氢化甘菊环的工作[11]过程中，我们现在选择了四环kempane 1-3作为具有挑战性的合成目标，分别具有7个和8个连续的立体中心，包括两个季碳原子。
Soldiers of the termite subfamily Nasutitermitinae found worldwide defend themselves against aggressors by ejecting a secretion containing structurally unique tetracyclic diterpenes.[1] Kempene-2 (1), kempene-1 (2), and 3-epi-kempene-1 (3) are diterpenes with a kempane skeleton isolated first from the defense secretion of termite soldiers of the species Nasutitermes kempae [2] and Bulbitermes singaporensis [3](Scheme 1).[4, 5] The synthesis of these exceptional natural products has proven to be problematic. So far, only the total synthesis of racemic kempene-2 (rac-1) has been reported,[6] whereas a number of other synthetic studies [7] have not yet led to the desired kempanes. Recently, we achieved the enantioselective synthesis of 4-desmethyl-3α-hydroxy-15-rippertene (5), a close analogue of rippertene 4, which was isolated fromNasutitermes rippertii and Nasutitermes ephratae; an intramolecular Diels–Alder reaction was the key transformation in the synthesis.[8] Recent studies [9] on the biological activity of 5 showed that this norditerpene exhibits an antibiotic activity against B. subtilis similar to that of antimicrobial trinervitanes.[10] In the course of our work [11] on the construction of hydroazulenes through domino metathesis reactions [12, 13] we have now selected the tetracyclic kempanes 1–3 as challenging synthetic targets with seven and eight contiguous stereogenic centers, respectively, including two quarternary carbon atoms.