Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene.
Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene.
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通过应变环状丙二烯的立体定向捕获来全合成 lissodendoric Acid A。
DOI：
10.1126/science.ade0032
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Garg,NeilK
中科院分区：
文献类型：
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作者：
Ippoliti,FrancescaM;Adamson,NathanJ;Wonilowicz,LauraG;Nasrallah,DanielJ;Darzi,EvanR;Donaldson,JoyannS;Garg,NeilK
含有丙二烯的小环是非常规的瞬态化合物，自 20 世纪 60 年代以来就已为人所知。尽管与苯炔大约在同一时间被发现并提供了许多合成上有利的特征，但应变环状丙二烯在化学合成中的用途相对较少。我们报告了曼扎明生物碱 lissodendoric Acid A 的简明全合成，该合成取决于快速环状丙二烯中间体的区域选择性、非对映选择性和立体特异性捕获的发展。这一关键步骤快速组装了天然产物的阿扎卡林框架，实现了简洁的合成终局，并实现了 12 步全合成（最长线性序列；总产率 0.8%）。这些研究表明，应变环状丙二烯是化学合成中的通用构件。
Small rings that contain allenes are unconventional transient compounds that have been known since the 1960s. Despite being discovered around the same time as benzyne and offering a number of synthetically advantageous features, strained cyclic allenes have seen relatively little use in chemical synthesis. We report a concise total synthesis of the manzamine alkaloid lissodendoric acid A, which hinges on the development of a regioselective, diastereoselective, and stereospecific trapping of a fleeting cyclic allene intermediate. This key step swiftly assembles the azadecalin framework of the natural product, allows for a succinct synthetic endgame, and enables a 12-step total synthesis (longest linear sequence; 0.8% overall yield). These studies demonstrate that strained cyclic allenes are versatile building blocks in chemical synthesis.