Why an apple a day keep the doctor away? Nature Is Truly Miraculous 8 wis the wild a 赤潮Red Tides 生叶联的不 生 Tetrodotoxin河豚毒素 “造尝世闻鱼万种，唯有河豚味最鲜 天然药物化学的应用 ◆探宗植物（中药）、动物，海洋生物等防我治南的物质基础 :发药有号化合牌 ，分析化号 Nature Is Also the Best Drug Designer
1 Why an apple a day keep the doctor away? Why an apple a day keep the doctor away? R2 HO R1 1 R1=OH, R2=CH3 2 R1=H, R2=CH3 3 R1=OH, R2=CH2OH R2 HO R1 4 R1=OH, R2=CH3 5 R1=H, R2=CH3 6 R1=OH, R2=CH2OH COOH RO HO OH 7 R= 8 R= C OH O C OH O CH2OH 9 HO RO OH O 10 R=H 11 R=CH3 HO O R2 O OH R1 12 R1=H, R2=OH 13 R1=OH, R2=H O O OH OH OH OH OH HO O 14 HO OH O O OH O HO O 15 16 HO OH OH OH HO O 17 HO O OH O OR OH OH 18 R=H 19 R=β-D-Gal 20 R=β-D-Glu 21 R=α-L-Ara O H OH OH HO OH OH 22 O H OH OH HO OH OH 23 H H H H Phlorizin 根皮苷 Nature Is Truly Miraculous Nature Is Truly Miraculous Many mushrooms that grow in the wild are poisonous or deadly, so don't go popping them! O N HO Muscarine毒蕈碱 1869 30多年来在云南北部每年7-9月雨季都发生几十例甚至更多的不明 原因猝死。2008年昆明植物所高等真菌化学专家刘吉开从云南一种新的 小白菌（Trogia sp.）中分离鉴定出了两个新的非蛋白质氨基酸: 2R-氨 基-4S-羟基-5-己炔酸，2R-氨基-5-己炔酸, 证明该菌是30多年来导致云南 不明原因猝死的罪魁祸首。 Science 2010, 329: 132-134 鹅膏毒素 a-Amanitin “死亡天使” (Death Angel):鹅 膏毒素 摧毁人们的肝和肾 OH O OH NH2 OH O NH2 赤 潮 Red Tides Red Tides Brevetoxin B 短裸甲藻毒素B Brevetoxin A Saxitoxin 石房蛤毒素 2008年在加拿大 产生赤潮的微藻 Alexandrium tamarense中检测 出5种石房蛤毒素 的类似物。 麻痹性贝毒 “suicide pills” Tetrodotoxin 河豚毒素 “遍尝世间鱼万种，唯有河豚味最鲜” The minimum lethal dose in an adult human is estimated to be 2-3 mg. Tetrodotoxin is a heat-stable and acid-stable, nonprotein, alkaloid toxin found in many species of the fish family Tetraodontidae (puffer fish) as well as in certain gobies, amphibians, invertebrates, and the blue-ringed octopus. N H N O O OH H NH HO OH HO OH H OH + 1 4 4a 8 10 11 6 Y. Kishi M. Isobe 天 然 药 物 化 学 的 应 用 u 探索植物(中药), 动物, 海洋生物等防病治病的物质基础 u 发现新药、寻找新药先导化合物 u 促进其他学科的发展—生命科学，有机化学，分析化学 Nature Is Also the Best Drug Designer ——Antibiotics and Anticancer
天然产物在抗肿瘤治疗中起普重要作用 “War on Cancer' 二者共占65%。 昌冒冒透图 1955 Dr.Wall Wani 心全裤！首草科值物 2
2 All available anticancer drugs, 1940s-06/2006, by source (N ) 175 A直接来源于天然产物的抗肿 瘤药物占14%；B 以天然产 物为先导进行全合成或半合 成而形成的抗肿瘤药物占 51%, 二者共占65%。 A B B B B C 天然产物在抗肿瘤治疗中起着重要作用 You need chemicals to fight cancer, and chemists have spent decades working on molecules they hope will fight everything from breast cancer to prostate cancer. But all the chemists in the world are no match for Mother Nature. “War on Cancer War on Cancer” Richard Nixon 1971 “National Cancer Act” N N O O O HO AcO OBz H OAc OH O O O OH Ph NH O O Taxol Taxus brevifolia Camptothecin Camptotheca acuminata 1958年美国NCI耗资250亿美元, 历时20多年(1958-1980年), 对 3500 余种植物中的11万多个提取物的抗癌活性进行了筛选。 喜树碱 Camptothecin 1958 Dr. Wall & Wani l0-Hydroxycamptothecin is used in China to treat cancers of the liver and stomach and also leukaemias. • ［来源］珙桐科植物喜树Camptotheca acuminata全株；茜草科植物 蛇根草Ophiorrhiza mungos叶。 • ［活性］抗肿瘤。对DNA拓扑异构酶I有明显抑制作用。 • Craig J. et al. Bioorg. Med. Chem. 2004,12 : 1585–1604. “靶向作用” 1966 高怡生1976 合成