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A Divergent Enantioselective Total Synthesis of Post-Iboga Indole Alkaloids |
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| Authors: | Jie Zhou Dong-Xing Tan Dr Fu-She Han |
| Institution: | 1. CAS Key Lab of High-Performance Synthetic Rubber and its Composite Materials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Remin Street, Changchun, Jilin, 130022 China
The University of Chinese Academy of Sciences, Beijing, 100864 China These authors contributed equally to this work.;2. CAS Key Lab of High-Performance Synthetic Rubber and its Composite Materials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Remin Street, Changchun, Jilin, 130022 China University of Science and Technology of China, Hefei, Anhui, 230026 China These authors contributed equally to this work.;3. CAS Key Lab of High-Performance Synthetic Rubber and its Composite Materials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Remin Street, Changchun, Jilin, 130022 China |
| Abstract: | Divergent enantioselective total syntheses of five naturally occurring post-iboga indole alkaloids, dippinine B and C, 10,11-demethoxychippiine, 3-O-methyl-10,11-demethoxychippiine, and 3-hydroxy-3,4-secocoronaridine, as well as the two analogues 11-demethoxydippinine A and D, are presented for the first time. The enantioenriched aza3.3.1]-bridged cycle, a common core intermediate to the target molecules, was constructed through an asymmetric phase-transfer-catalyzed Michael/aldol cascade reaction. The challenging azepane ring fused around the indole ring and the 3.3.1]-bridged cycle were installed through an intramolecular SN2′-type reaction. These cyclization strategies enabled rapid construction of the 6.5.6.6.7]-pentacyclic core at an early stage. Highlights of the late-stage synthetic steps include a Pd-catalyzed Stille coupling and a highly stereoselective catalyst-controlled hydrogenation to incorporate the side chain at C20 with both R and S configurations in the natural products. |
| Keywords: | cascade reactions divergent synthesis indole alkaloids Stille coupling total synthesis |