河北医科大学药学院 What Can Organic Chemist Do With NP? ® First Bio-mimic Synthesis C.E-a 9T5 9 ic total synthesis of iropinone (Robiaso,1917) What Can Organic Chemist Do With NP? Mimic Synthesis inspiration for Nature Ne0,C. 裙a个特2机 查宁的合成与苯胺紫 1944年《但的时》作为头条新阳通 合成妻宁开启的染料时尺-电阿楼影响丁医学和喷胺药物的发乳 (13塔-190万 a 天然药物化学教研室史清文教授 13 河北医科大学药学院 天然药物化学教研室史清文教授 13 "We have only just touched the tip of the iceberg in terms of molecular diversity from nature," says Nicolaou. Biomimetic total synthesis of tropinone (Robinson, 1917) Robinson, R. J. Chem. Soc., Trans. 1917, 762. Robinson, R. J. Chem. Soc., Trans. 1917, 762. See also: Birch,A. J. Notes Records Royal Soc. London 1993, 47, 277. First Bio-mimic Synthesis 1886-1975 1947年Nobel Prize R. Robinson CHO CHO + H2NMe + COOH COOH O Aqua N O Me What Can Organic Chemist Do With NP? What Can Organic Chemist Do With NP? 英国Nottingham 大学的Gerald Pattenden发明了用一步反应合成甾体化 合物四个环和7个手性中心的简易巧妙方法。 Gerald Pattenden Nature, 2008, 445, 323-332. Natural products as inspiration for the development of asymmetric catalysis SePh CH3 CH3 CH3 H CH3 H O O n-Bu2SnH, AlBN Heat Redical cascade H CHO OHC HN i) CH3NH2 ii) AcOH 65% C.H. Heathcock see PNAS 1996, 63, 14323 Methyl Homosecodaphniphyllate Daphniphyllum macropodum 虎皮楠 C.H. Heathcock Science, 1990, 248, 1532-1534. Mimic Synthesis inspiration for Nature 317 A.W. von Hofmann (1818 – 1892) 1856 N N H H HO H3CO H Quinine N NH+ H3C CH3 CH3 N CH3 H3C Cl - 奎宁的合成与苯胺紫 法国皇后 Eugenie 1908 William Perkin (1838–1907) 合成奎宁开启的染料时代-也间接影响了医学和磺胺药物的发现 318 人工合成奎宁到1944年才取得了重大突破。为了解决第二次世界大战 造成的奎宁短缺，R. B. Woodward和William E. Doering成功地合成了奎宁 毒(D-quinotoxin)。一种被认为可以转化成奎宁的中间体。这个合成被有机 化学界认为是一个有机合成史上的里程碑式的成就。结束了对奎宁合成长 达100年的探索。 Woodward and Doering, discuss the synthetic scheme for quinine in May 1944 1944年《纽约时报》作为头条新闻报道 “The Woodwardian era” of organic chemistry