State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Org Lett. 2021 Apr 2;23(7):2731-2735. doi: 10.1021/acs.orglett.1c00638. Epub 2021 Mar 18.
Herein we report a streamlined, gram-scale total synthesis of (-)-colchicine that takes only 7 easy steps, with an overall yield of 27-36%. To warrant the synthetic efficiency and practicality of (-)-colchicine, we tactically utilized a modified version of a powerful Ir-catalyzed amidation reported by Carreira to install the key chiral C-7 acetamido group, Suzuki and biomimetic phenol oxidative coupling, and Banwell-inspired cyclopropane ring cleavage to construct (-)-colchicine precisely and rapidly. Remarkably, a described strategy also can shorten the synthesis of allocolchicinoid to 4 steps.
在此，我们报告了 (-)-秋水仙碱的简化、克级规模的全合成，只需 7 步即可完成，总收率为 27-36%。为了保证 (-)-秋水仙碱的合成效率和实用性，我们巧妙地利用了 Carreira 报道的一种经过改良的强大的 Ir 催化酰胺化反应来引入关键的手性 C-7 乙酰氨基，通过 Suzuki 和仿生酚氧化偶联以及 Banwell 启发的环丙烷环裂解来精确快速地构建 (-)-秋水仙碱。值得注意的是，所描述的策略还可以将全表秋水仙碱类似物的合成缩短至 4 步。
