What Can Organic Chemist Do With NP? Mimic Synthesis 8 虎皮 Bio-Synthesis 天然产物化学促进生命科学的发展 无脑产物作为化和生之一十天通，是大自过 的医 人人 Natural Products as Chemical Probes 没有天然产物没有分子生物学的今天 ra六2 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 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 Mimic Synthesis HOOC O OH O O O O O O O O O O CHO HO H O O O O O O O H H O O O O O O O O O O O Me O HO Me Me Me Me Me Me H H H H H H H H H H H H H H H CHO Epoxide-opening Ring closure Cascade Epoxidation Bio-Synthesis Synthesis 天然产物作为化学和生物学之间一个天然的通道，是大自然经过漫 长的筛选和进化选择出来的。生命科学的发展急需应用新的小分子作为 分子探针去帮助研究已知的生物反应机理，去发现尚未被阐明的生物作 用机理，去验证全新的生物药物靶点，和去解决重大的医学难题。天然 产物作为化学小分子探针做出了其他生物技术方法无法企及的特殊贡 献，并此催生了一门新的学科——(天然产物)化学生物学。 天然产物化学促进生命科学的发展 Erin E. Carlson. Natural Products as Chemical Probes. ACS Chem. Biol. 2010, 5, 639-653. Stuart L. Schreiber, Harvard Uni. Natural Products as Chemical Probes Natural Products as Chemical Probes 没有天然产物就没有分子生物学的今天? Microtubule-stabilizing Agents from Nature “Dear Monroe: Can you help this poor girl?” Nature 1979, 277: 665-667 Her landmark research would help turn the molecule into one of the world’s most effective anti-cancer blockbuster drugs. O OH OH H O HO OH O NH2 O Discodermolide OH O O HO OH OH 1 6 16 Dictyostatin O O HO R O O N S OH Epothilone A R=H Epothilone B R=CH3 O O Me O H H N N Me OMe Eleutherobin O O OH AcO OH O O HO OH H H H O H FR182877 O O O H H OH H O H O H HO Laulimalide O OH HO OMe O O OH OMe OH Me Me HO Peloruside A MeO O O Me O COOMe H H N N Me OH Sarcodictyin A