Total Syntheses of Lyconadins A-C
Total Syntheses of Lyconadins A-C
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DOI：
10.1021/ja312065m
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发表时间：
2013-02-27
影响因子：
15
通讯作者：
Fukuyama, Tohru
中科院分区：
文献类型：
--
作者：
Nishimura, Takuya;Unni, Aditya K.;Fukuyama, Tohru
完成了石松属生物碱石松苷A的全合成，并将其应用于石松苷B和C的全合成。由于其独特的五环骨架结构，使其成为全合成中极具挑战性的目标化合物。我们合成的石蒜苷A的特点是通过氮杂-普林斯反应和电环开环的组合，然后形成一个C-N键的高度稠合的四环骨架的一个简单的建设。广泛研究了四氢呋喃的溴代烯烃部分转化为关键烯酮中间体，并建立了三种通过硫化物，肟或叠氮化物中间体的方法。从关键的烯酮中间体构建吡啶酮环，完成了石蒜素A的合成。二氢吡啶酮环也可以从相同的烯酮中间体形成，导致合成石蒜素B。建立了不形成C-N键的电环开环条件，完成了石蒜素C的全合成。
The total synthesis of the Lycopodium alkaloid lyconadin A was accomplished and it was applied to the total syntheses of the related congeners, lyconadins B and C. Lyconadin A has attracted attention as a challenging target for total synthesis due to the unprecedented pentacyclic skeleton. Our synthesis of lyconadin A features a facile construction of the highly fused tetracyclic skeleton through a combination of an aza-Prins reaction and an electrocyclic ring opening, followed by formation of a C-N bond. Transformation of the bromoalkene moiety of the tetracycle to a key enone intermediate was extensively investigated, and three methods via sulfide, oxime, or azide intermediates were established. A pyridone ring was constructed from the key enone intermediate to complete the synthesis of lyconadin A. A dihydropyridone ring could also be formed from the same enone intermediate, leading to a synthesis of lyconadin B. Establishment of the conditions for an electrocyclic ring opening without formation of the C-N bond resulted in completion of the total synthesis of lyconadin C.