手性合成埃伯那明、叶树碱和 16'-表叶树碱。
The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16'-epi-Leucophyllidine.
机构信息
Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, 1200 E. California Blvd, MC 101-20, Pasadena, CA, 91125, USA.
Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok, 10210, Thailand.
出版信息
Angew Chem Int Ed Engl. 2021 Aug 9;60(33):17957-17962. doi: 10.1002/anie.202106184. Epub 2021 Jul 6.
Abstract
A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium-catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine-derived fragment was synthesized through a Bischler-Napieralski/hydrogenation approach, while the eucophylline-derived fragment was synthesized by Friedländer quinoline synthesis and two sequential C-H functionalization steps. A convergent Stille coupling and phenol-directed hydrogenation united the two monomeric fragments to afford 16'-epi-leucophyllidine in 21 steps from commercial material.
摘要
本文公开了一种杂二聚双吲哚生物碱莱苏定的合成方法。通过钯催化的不对称烯丙基烷基化反应合成的对映体富集的内酰胺砌块，作为两个半球的前体。伊布纳明衍生片段通过 Bischler-Napieralski/氢化方法合成，而 eucophylline 衍生片段通过 Friedländer 喹啉合成和两个连续的 C-H 官能化步骤合成。一个收敛的 Stille 偶联和酚导向的氢化将两个单体片段联合起来，从商业原料中以 21 步得到 16'-表莱苏定。
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