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Asymmetric synthesis of ABC tricyclic systems in Daphniphyllum alkaloid
Authors:Huijing Wang  Qiuyan Dong  Qinxia Xie  Pei Tang
Institution:1. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China;2. Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China;3. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla 92093-0934, United States;1. Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey;2. Department of Chemistry, Abant İzzet Baysal University, 14280 Bolu, Turkey;1. Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;2. Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;3. Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan;4. Lead Chemical Co. Ltd, 77-3 Himata, Toyama 930-0192, Japan;1. Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China;2. Institutes of Biomedical Sciences, Fudan University, 130 Dongan Road, Shanghai 200433, China;3. PET Center, Huashan Hospital, Fudan University, 518 East Wuzhong Road, Shanghai 200235, China;1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, People''s Republic of China;2. The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China;3. Laboratory of Chemical Genomics, Shenzhen Graduate School of Peking University, Shenzhen 518055, People''s Republic of China;4. Yunnan Academy of Tobacco Science, Kunming 650106, Yunnan, People''s Republic of China
Abstract:Efficient synthetic routs for the direct and rapid construction of5-6-6] ABC tricyclic systems of daphmanidin A-type and calyciphylline A-type alkaloids have been successfully developed. For the daphmanidin A-type, the synthesis of5-6-6] tricyclic framework utilize a HCl-mediated intramolecular Aldol reaction to construct the bicyclo2.2.2]octane core and a thermal condensation to afford the ABC ring system. In addition, for the calyciphylline A-type, an improved synthesis of ABC5-6-6] tricyclic system was developed, featuring an introduction of methyl ester group at C2 before the Pd-catalyzed intramolecular oxidative alkylation to construct the desired bowl-shape tricyclic core with stereochemical control.
Keywords:Daphniphyllum alkaloid  Calyciohylline N  21-Deoxymacropodumine D  ABC tricyclic framework  Intramolecular Aldol reaction  Pd-catalyzed intramolecular oxidative  alkylation  
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