State Key Laboratory of Coordination Chemistry, and Jiangsu Key Laboratory of Advanced Organic Materials School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, Nanjing, Jiangsu 210023, China.
J Org Chem. 2022 Jul 1;87(13):8685-8696. doi: 10.1021/acs.joc.2c00871. Epub 2022 Jun 14.
A unified route for the total synthesis of three tetracyclic diquinane alkaloids (+)-paniculatine, (-)-magellanine, and (+)-magellaninone has been accomplished in 13-14 overall steps based on late-stage diverse transformations from an advanced tetracyclic common intermediate. In the established synthesis, quick formation of the two five-membered rings was efficiently achieved by an intramolecular reductive coupling of ketone-carbonyl and ester-carbonyl and an organocatalytic intramolecular Michael addition of aldehyde-derived enamine to an internal enone functionality with satisfactory redox and step economies and excellent stereoselectivities, providing the requisite tricyclic carbo-framework possessing multiple dense stereogenic centers, and an intramolecular reductive amination finally furnished the essential piperidine ring.
已经完成了三种四环二氢喹啉生物碱（+）-paniculatine、（-）-magellanine 和（+）-magellaninone 的总合成的统一路线，该路线基于晚期多样化转化，从高级四环共同中间体出发，共经过 13-14 步。在建立的合成中，通过酮羰基和酯羰基的分子内还原偶联以及醛衍生的烯胺与内部烯酮官能团的有机催化分子内迈克尔加成，有效地快速形成了两个五元环，具有令人满意的氧化还原和步骤经济性以及出色的立体选择性，提供了必需的具有多个密集立体中心的三环碳骨架，并通过分子内还原胺化最终得到了必需的哌啶环。
