河北医科大学药学院 西加毒素(Ciguatoxin Developing New Methodology for Total Synthesi 6 平间正博 liram M.2001.:1904 Total Synthesis of PTX Total Synthesis of Tetrodotoxin HO 1972 段金技'ue (-)-Palau'amine H 天然药化教研室史清文教授 8 河北医科大学药学院 天然药化教研室史清文教授 8 Hirama M. Science 2001, 294: 1904. 平间正博 PNAS, 2004,101, 12013–12018. 西加毒素 (Ciguatoxin) After a twelve-year struggle, the total synthesis of ciguatoxin CTX3C has been achieved. Shi epoxidation 80% 20% O BuO O t- O BuO O t- O O O O BF3 1. BF3 Et2O 2. H2O O O O O O O H H H H OH ... Scheme 1. Lewis acid promoted epoxide-opening cascade to give fused polyoxepane systems. （1） 硒诱导的关环反应 （2） 基于硫代糖苷的糖化反应， （3） 环醚化反应 （4） 基于IBX- 和DMP的氧化反 应 和环化反应 （5）大环成环反应 （6）金属催化和无机催化的不 对称环化反应等等都是具 有代表性的工作 (7) Yamaguchi macrolactonization (8) Grubbs’s ring-closing metathesis (RCM) Developing New Methodology for Total Synthesis Minoru Isobe. Nat. Prod. Rep., 2010, 27, 1204-1226. Armstrong R. W. Kishi et al. J. Am. Chem. Soc. 1989, 111: 7530. Totalsynthesis “珠穆朗玛峰的攀登” 64 C* & 7db 21 P-PhD and Dr. Students spend more than 8 years 岸 义人教授1937-，歧阜人，名大毕业，哈佛 教授载入美国化学会过去75最伟大的化学研究 Total Synthesis of PTX O OH OH OH HO O OH OH O HO OH OH OH OH O OH HO OH OH OH OH O O O OH NH2 HO OH O O O OH OH OH HO OH OH HO OH HN O NH OH O OH OH OH OH OH HO OH OH OH OH OH OH OH Total Synthesis of Tetrodotoxin Yoshito Kishi Racemic Total synthesis in 1972 Asymmetric Total in 2003 N H N O O OH H NH HO OH HO OH H OH + 1 4 4a 8 10 11 6 矶部惗 Prof. Yoshito Kishi 岸 义人 Emeritus Department of Chemistry and Chemical Biology Harvard University Robert Woodward博士生 岸义人 N H N OO OH H NH HO OH HO OH H OH + 1 4 4a 8 10 11 6 福山 透 1977 Ph.D Harvard University (Prof. Y. Kishi) Prof. Pharmaceutical Sciences University of Tokyo (-)-Palau’amine Kinnel, R. B.; Gehrken, H.-P.; Scheuer, P. J. J. Am. Chem. Soc. 1993, 115, 3376-3377. Thomas Lindel, et al. Study on the absolute configuration of (-)-palau’amine. Tetrahedron Lett. 2010, 51, 6353-6355. Total Synthesis of Palau'amine, Angew. Chem. Int. Ed. 2010, 49, 1095-1098. Phil S. Baran Barab, P. S. Angew. Chem. Int. Ed. 2010, 49, 1095-1098. J. Org. Chem., 2010, 75, 4657-4673. N N HN NH HN NH NH2 NH2 H H Cl O OH H2N H 9个氮原子和8个手性中心