One-Carbon Insertion and Polarity Inversion Enabled a Pyrrole Strategy to the Total Syntheses of Pyridine-Containing Lycopodium Alkaloids: Complanadine A and Lycodine,Journal of the American Chemical Society

当前位置： X-MOL 学术 › J. Am. Chem. Soc. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

One-Carbon Insertion and Polarity Inversion Enabled a Pyrrole Strategy to the Total Syntheses of Pyridine-Containing Lycopodium Alkaloids: Complanadine A and Lycodine
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-09-27 , DOI: 10.1021/jacs.1c08626
Donghui Ma ₁ , Brandon S Martin ₁ , Katelyn S Gallagher ₁ , Takeru Saito ₁ , Mingji Dai ₁

Affiliation

Complanadine A and lycodine are representative members of the Lycopodium alkaloids with a characteristic pyridine-containing tetracyclic skeleton. Complanadine A has demonstrated promising neurotrophic activity and potential for persistent pain management. Herein we report a pyrrole strategy enabled by one-carbon insertion and polarity inversion for concise total syntheses of complanadine A and lycodine. The use of a pyrrole as the pyridine precursor allowed the rapid construction of their tetracyclic skeleton via a one-pot Staudinger reduction, amine-ketone condensation, and Mannich-type cyclization. The pyrrole group was then converted to the desired pyridine by the Ciamician–Dennstedt rearrangement via a one-carbon insertion process, which also simultaneously introduced a chloride at C3 for the next C–H arylation. Other key steps include a direct anti-Markovnikov hydroazidation, a Mukaiyama–Michael addition, and a Paal–Knorr pyrrole synthesis. Lycodine and complanadine A were prepared in 8 and 11 steps, respectively, from a readily available known compound.

中文翻译：

一碳插入和极性反转使吡咯策略能够全合成含吡啶的石松生物碱：Complanadine A 和 Lycodine

Complanadine A 和 Lycodine 是石松属生物碱的代表成员，具有特征性的含吡啶四环骨架。 Complanadine A 已被证明具有良好的神经营养活性和治疗持续性疼痛的潜力。在此，我们报告了一种通过单碳插入和极性反转实现吡咯策略，用于简明全合成complanadine A和lycodine。使用吡咯作为吡啶前体可以通过一锅施陶丁格还原、胺酮缩合和曼尼希型环化快速构建其四环骨架。然后通过一碳插入过程进行 Ciamician-Dennstedt 重排，将吡咯基团转化为所需的吡啶，同时在 C3 处引入氯化物以进行下一个 C-H 芳基化。其他关键步骤包括直接反马尔可夫尼科夫氢叠氮化、Mukaiyama-Michael 加成和 Paal-Knorr 吡咯合成。 Lycodine 和 compladine A 分别由容易获得的已知化合物通过 8 步和 11 步制备而成。

更新日期：2021-10-13

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南