Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.
Science. 2023 Jan 20;379(6629):261-265. doi: 10.1126/science.ade0032. Epub 2023 Jan 19.
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.
含有丙二烯的小环是非传统的瞬态化合物，自 20 世纪 60 年代以来就为人所知。尽管它们与苯炔同时被发现，并具有许多合成上的优势，但环状丙二烯在化学合成中的应用相对较少。我们报告了曼扎明生物碱 Lissodendoric Acid A 的简洁全合成，该合成的关键在于对短暂的环状丙二烯中间体进行区域选择性、非对映选择性和立体特异性捕获的开发。这一关键步骤迅速组装了天然产物的氮杂双环[3.2.1]辛烷骨架，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；总产率为 0.8%）。这些研究表明，环状丙二烯是化学合成中多功能的构建模块。
