河北医科大学药学院 MS,NMR,X-Ray与结构鉴定 天然产物化学结构研究与诺贝尔化学奖修心 化合物的结构鉴定重要吗？ Why? 有多少科学家因结构研究获得诺贝尔奖？ 茶是上 What Is Structure Elucidation? Structure Elucidation only finding where chemical bomds are but also how they are spatially arranged in the relative as well as in the m of a m s History of Structure Elucidation What are the tools which permit solving chemical structure? ◆Elemental analysis ◆飞lass spertrometry Ultra Violt,Infra Red,Raman,Circular Dichroism Nuelear Magnetic Resonance NMR 、 proton,carbon-13,1D-NMR.2D-NMR ◆X-ray diffraction Betwcen1920-195 ◆Chemistry-.Chemical degra山ion and Total 天然药物化学室史清文教授 6 河北医科大学药学院 天然药物化学室史清文教授 6 化合物的结构鉴定重要吗？ Why？ 有多少科学家因结构研究获得诺贝尔奖？ Robert Robinson 吗啡、马钱子碱 James Dewey Watson DNA Dorothy Hodgkin 青霉素、维生素B12 R. B. Woodward 河豚毒素、土霉素 Before 1950s, structure studies were life-long Nobel Prize-winning activities MS, NMR, X-Ray与结构鉴定 因阐明糖和嘌呤(purine)的结构而获奖 因阐明靛蓝(indigo)的结构而获奖 因研究植物色素包括叶绿素(chlorophy)的结构而获奖 因阐明胆酸(bile acid)等甾体化合物的结构而获奖 因在甾体化合物结构鉴定及阐明甾体化合物和维生素D结构关系方面的工作而获奖 因在血红素和叶绿素结构研究方面的工作而获奖 因在维生素C结构阐明和糖的Haworth投影方面的工作而获奖 因在维生素A和B2结构研究方面的工作而获奖 因在类胡萝卜素和维生素方面的工作而获奖 因在胰岛素发现和结构鉴定方面的工作而获奖， 因在核酸结构测定方面的工作而二次获奖 因在维生素B12、青霉素和胰岛素结构鉴定方面的工作而获奖 因在众多化合物的结构鉴定和合成方面的工作而获奖 因在肌红蛋白(myoglobin)和血色素(haemoglobin)方面的工作而获奖 因在甾体激素、信息素和萜类化合物以及古老 的香水成分灵猫酮(civetone)的结构而获奖 因在马钱子碱、花青素和吗啡等生物碱的结构鉴定方面的工作而获奖 Emil Fischer (1852-1919) Adolf von Baeyer(1835-1917) Richard M. Willstätter(1872-1942) Heinrich Wieland (1877-1957) Adolf R. Windaus (1876-1959) Hans Fischer (1881-1945) Norman Haworth (1883-1950) Paul Karrer (1889-1971) Richard Kuhn (1900-1967) Adolf F. J. Butenandt (1903-1995) Leopold Ruzicka (1887-1976) Robert Robinson (1886-1975) Frederick Sanger (1918-2013) Max Perutz (1914-2002) John Kendrew (1917-1997) Dorothy Hodgkin (1910-1994) Robert B. Woodward (1917-1979) 1938 1902 1930 1939 1962 1927 1937 1928 1915 1905 天然产物化学结构研究与诺贝尔化学奖 1947 1958 1980 1964 1965 33 What Is Structure Elucidation? From a chemist’s standpoint, a structure is a three dimensional array of atoms and solving a structure is not only finding where chemical bonds are but also how they are spatially arranged in the relative as well as in the absolute mode. Finally, molecules have mobility and therefore conformation around bonds and in rings must be defined also. 34 Structure Elucidation During all of the 19th century and most of the early half of the 20th century, natural product structure elucidation was an art that depended almost entirely on the power of chemical synthesis, or, more specifically, on the effectiveness of degradation or derivatization processes, to reveal the architectural design of a molecule. Assuming both that gram quantities of the substance under investigation were available and that the chemical transformations employed proceeded along expected lines, researchers of that era might have expected to solve their molecular puzzles after a few years of painstaking effort. 35 History of Structure Elucidation Amount of the sample, time and precies Before 1920——化学、常量分析——大师、诺贝尔奖 Between 1920-1950——微量分析——大师、诺贝尔奖 After 1950——仪器分析——专家、研究生、技术员 36 What are the tools which permit solving chemical structure?  Elemental analysis  Mass spectrometry  Ultra Violt, Infra Red, Raman, Circular Dichroism  Nuclear Magnetic Resonance NMR proton, carbon-13, 1D-NMR, 2D-NMR  X-ray diffraction  Chemistry-Chemical degradation and Total Synthesis