天然药物化学 必孕急金 心透拼8 料* 的彩 叠2空裘 条 Drugs From The Sea 第十五章 海洋天然产物 TARINENATURAL PRODUGTS 海洋天然产物 试只 Marine Natural Products(MNP) What are they? Why do we care MNP? What/How do we study?
1 1 O O O O H CH3 H CH3 O H H3C 15 Artemisinin O N MeO Me HO H 3 Galantamine HO AcO OBz H OAc OH O O O OH Ph NH O O HO O HO N H CH3 N N H H HO H3CO H 1 Quinine 12 Morphine 10 Taxol N N O O O 11 Camptothecin O O OH HO 13 Daidzein HO O O HO 14 Esculetin HO OH H O O 9 Digitoxigenin H Glc-O H H H 8 Ginsenoside Rg3 H OH OH Glc O O O 2 Tanshinoe IIA O O OH OH OH OH OH OHOH OH O 6 Sucrose OH 4 Borneol OH 5 Menthol 7 Parthenolide O O O 天 然 药 物 化 学 2 CO2H O H H HO N O N H O N O N O NH O S N H O H H H Br H OAc AcO OAc OH H H O I O O O O O O O O O O O O O OH O O O OH O O O O HO OH O OH S O O ONa HO OH OH OH OH OH O S O ONa HO OH O H H H H H H H HO H H H H H H H H OH OHH H H H H H OH H OH HO OH H H OH H H OH OH H H HO H H H H H O O O O O O O H OH H H H H H H H H HO H A O O O O HO OH H H H H H H O O O HO OH H H O O Br H H O H OH OH H H HO H OH O O HO OH OH 3 Drugs From The Sea ? Drugs From The Sea ? 4 第 十 五 章 MARINE NATURAL PRODUCTS MARINE NATURAL PRODUCTS 海 洋 天 然 产 物 史 清 文 2014-6-25 5 Marine Natural Products (MNP) Marine Natural Products (MNP) What are they? Why do we care MNP? What/How do we study? 海 洋 天 然 产 物 6 Earth of 21 Earth of 21th Century Century 地球只有一个——停止自己的贪婪 If the west coast forests had been harvested 50 years ago, paclitaxel （Taxol) would not have been discovered
Loss of Biodiversity 海洋天然产物 Purpose and Aim 天统 点、分岁 。了解其生物活 道廉藏类化合物的结构转点、分类，了解其生物活性 5了解散类的结构特点、分类和生物活性！ 子拳運前列康秦类化合物结构特点：了解其生物活性： 了解C:,乙酸原类化合物的结构特点： Recommended References Che 921Nat o 200 972- All PDF Files Are Available in Our Lab 推荐参考书：管华诗《中华海洋本草)209 《海洋药物导论》 易杨华上海科学技术出版社，2004 《海弹天然产物》 林文偏化学工业出版社，2006 天然
2 7 • ~ 100 species/day is lost • Loss potential of medicines Loss of Biodiversity Loss of Biodiversity Human health is inseparable from the health of the natural world. A species that seemed unimportant to us today may become an extremely valuable economic resource tomorrow. The loss of a species from the natural world is permanent 8 Purpose and Aim 1 了解开展海洋天然产物研究的现状和意义； 2 了解海洋天然产物研究的主要对象; 3 掌握大环内酯类的结构特点、分类，了解其生物活性； 4 掌握聚醚类化合物的结构特点、分类，了解其生物活性； 5 了解肽类的结构特点、分类和生物活性； 6 掌握前列腺素类化合物结构特点；了解其生物活性； 7 了解C15乙酸原类化合物的结构特点； 海 洋 天 然 产 物 9 1. D. John Faulkner. Highlights of Marine Natural Products Chemistry (1972–1999). Nat. Prod. Rep., 2000, 17, 1-6. 2. Gerald Blunden. Biologically Active Compounds from Marine Organisms. Phytother. Res. 2001, 15, 89-94. 3. David J. Newman and Gordon M. Cragg. Marine Natural Products and Related Compounds in Clinical and Advanced Preclinical Trials. J. Nat. Prod. 2004, 67, 1216- 1238. Recommended References All PDF Files Are Available in Our Lab 10 D. John Faulkner. Highlights of Marine Natural Products Chemistry (1972–1999). Nat. Prod. Rep., 2000, 17, 1-6. 11 12 《海洋药物的研究与开发》 张朝辉 人民卫生出版社，2003 《海洋药物导论》 易杨华 上海科学技术出版社，2004 《海洋天然产物》 林文翰 化学工业出版社，2006 《功能海洋生物分子—发现与应用》 谭仁祥 科学出版社, 2007 《海洋天然产物的分离纯化与结构鉴定》 邓松之 化学工业出版社，2007 推荐参考书： 管华诗《中华海洋本草》2009
课外读物 第一节概述 。海洋天然产物化学研究的历史回顾 INTRODUCTION 史清文，霍长虹，李力更，张媛丽 一、海洋知多少How much do you learn? 中草药，2009,4011)1687-1695 二、海洋生物的特点Characteristics of MNP 。海洋天然产物化学研究概述 三、海洋天然产物的研究摄况Outline of MNE 史清文，李力更，蛋长红，张馒丽，王于方 四、海洋天然产物研究的意义Meaning of MNF 中草药，2010,41(7少1031-1047. 五、海洋天然产物研究的对象Objects of MNP http://202.206.48.73/tryw1/default.asp, 第一节概述 Ocean Is A Desert of Organisms? INTRODUCTION 一、海洋知多少？How much have you learn about ocean 海洋一最大的性命相愿地 。..w Ocean Habitat Diversity A Rich Treasure Chest of New Medicinal Produ 中有丰喜多烨的 上的 ,无论
3 13 课 外 读 物 ☞ 海洋天然产物化学研究的历史回顾 史清文，霍长虹，李力更，张嫚丽 中草药，2009，40(11): 1687-1695. ☞ 海洋天然产物化学研究概述 史清文，李力更，霍长虹，张嫚丽，王于方 中草药，2010，41(7): 1031-1047. http://202.206.48.73/tryw1/default.asp 14 第一节 概 述 INTRODUCTION 一、海洋知多少 How much do you learn? 二、海洋生物的特点 Characteristics of MNP 三、海洋天然产物的研究概况 Outline of MNP 四、海洋天然产物研究的意义 Meaning of MNP 五、海洋天然产物研究的对象 Objects of MNP 15 INTRODUCTION 一、海洋知多少？How much have you learn about ocean? Northern Hemisphere Southern Hemisphere Equator 61% 81% 第一节 概 述 16 Ocean Is A Desert of Organisms? Ocean Is A Desert of Organisms? Life on earth has its origin in the sea. Although the diversity of life in the terrestrial environment is extraordinary, the greatest biodiversity is in the world’s oceans. The oceans cover more than 70% of our planet’s surface and contain more than 500000 species of plants and animals. 海洋——最大的生命栖息地 17 Caves Polar Coral Reef Kelp Forest Deep Sea Volcano Ocean Habitat Diversity 18 A Rich Treasure Chest of New Medicinal Products 海洋中有丰富多样的生物物种，其品种是陆地上的两倍以上，无论 大小、软硬、抑或速度快慢，都能生存下来，这说明它们有天然自卫、 抵抗疾病的能力。特别是那些身上充满生物活性分子、利用化学方式保 护自己的海洋物种，很可能蕴含丰富的药物资源，开发价值不可估量
海洋3.6亿多平方公里， Why Produce Marine Natural Produets The purpose of matural prodacts is to provide the 用 >我国海岸线：1S00eKm,高与海米14000Km 葡房” 海洋生物有哪些？ 海洋植物 Plants in Ocean 1.海洋植物 2.海洋动物类 低等的藻类植物：Ag℃ 高等的种子植物：红树林 3.海洋微生物 (Mao 海洋到物类 海洋微生物 Marine Microorganisms ☒ 天物 天动门 4
4 19 v海洋3.6亿多平方公里. v海洋生物种类: 34门(32 Phyla occur in the sea and 17 on land) 50万种 v海洋生物量占地球总生物量: 87% , 利用率 2% v我国海岸线:18000 Km, 岛屿海岸线14000 Km v我国海域面积:470 多万平方公里 v浩瀚的海洋将是人类未来的“大药房”。 20 • The purpose of natural products is to provide the organism with an advantage over its neighbors. Why Produce Marine Natural Products Why Produce Marine Natural Products Because of their longer evolutionary history, marine organisms likely posses a greater molecular diversity than do their terrestrial counterparts. Studies from around the world have shown that marine organisms produce a diverse array of metabolites with novel chemical structures and potent biological activities as well as other desirable properties. 21 海洋生物有哪些？ 1. 海洋植物 2. 海洋动物类 3. 海洋微生物 22 海 洋 植 物 Plants in Ocean 低等的藻类植物：Algae 高等的种子植物：红树林 (Mangrove) 藻类(Algae)植物的大小极为悬殊。最小的单细胞藻类个体很小很小，只有 在显微镜下才能看到它们；而最大的巨藻身长可达二三百米，完全可以称 得上是庞然大物。海洋中的种子植物，如大叶藻、红树等，种类很少。 23 海洋动物类 海绵动物 Sponges 腔肠动物 Coelenterates 软体动物 Molluscs 棘皮动物 Echinoderms 环节动物 Annelida 节肢动物 Arthropoda 脊椎动物门 Vertebrates 无脊椎动物门 Invertebrates Animals in Ocean 24 海 洋 微 生 物 Marine Microorganisms 细 菌 Bacteria 真 菌 Actinomycetes Fungi 放线菌 微藻 Microalgae
二、Features of Marine Organisms 1.Unique Environment of Marine Living Thing What's difference between marine oganinssntiriahrteetnial organism and terrestrial organisms? Higher salt comtent (High salinity) Sea Has Higher Biodiversity Than Land 清赛”餐米以下水 5059m trr 065 网：英因科学家从深度达到的 最新海洋生物普查 5
5 25 二、Features of Marine Organisms Features of Marine Organisms What’s difference between marine organism and terrestrial organisms? Sea Has Higher Biodiversity Than Land 26 1. Unique Environment of Marine Unique Environment of Marine Living Things Living Things Marine organisms survive in the terrestrially unusual conditions u Higher salt content (High salinity) u Low or zero light and limited oxygen u Poor nutrition u High pressure u Unusually high or low/constant temperatures Deep-sea marine fauna. (A) A Bolocera sp. anemone (500 m depth, Barents Sea, Norway); (B) A community of anemones, hydroids and corals (100 m depth, North Sea, UK); (C) The basket star Gorgonocephalus caputmedusae (930 m depth, Norway); (D) A colony of the deep-water coral Lophelia pertusa (100 m depth, North Sea, UK). 27 HN O NH O 1 HN O NH O 2 Gram-positive bacterium obtained from 5065 m deep ocean sediment from the Central Pacific Basin, the deepest reported sample from which a new natural product has been isolated. Both exhibit significant cytotoxicity against human tumour cell lines, as well as moderate antiviral activity against Herpes simplex virus-II (HSV-II). B. S. Davidson and R. W. Schumacher, Tetrahedron, 1993, 49, 6569. 5065 m “海魔” 一种只能在2700米以下水域 找到的怪异生物 28 A deep-sea fungus, Phialocephala sp., obtained at a depth of 5059 m, has yielded the novel metabolite trisorbicillinone A, bearing a unique trimeric sorbicillin skeleton, and exhibiting significant cytotoxicity towards murine P388 and HL60 cells (IC50=9.10 and 3.14 mM, respectively). The same group identified a further two new antineoplastic antibiotic bisorbicillinoids from the same sample, designated oxosorbiquinol and dihydrooxosorbiquinol. D. Li, F. Wang, X. Xiao, et al. Tetrahedron Lett., 2007, 48, 8083 and 5235. 5059 m 29 2007年8月26日美国生活科学网:英国科学家从深度达到约 3500米的海域中新发现了一些非常奇特的海洋生物。 “The Deep-Sea Biodiversity holds major promise for the treatment of human diseases” ---Dr. Sara Maxell, Medicines from the Deep, 2005 30 • 历时10年的全球“海洋生物普查”项目2011年10月4日在伦敦发布最终报 告： 根据普查得出的统计数据，海洋生物物种总计约100万多种，其中25 万种是人类已知的海洋物种，其他75多万种海洋物种人类知之甚少，这些 人类不甚了解的物种大多生活在北冰洋、南极和东太平洋未被深入考察的 海域。丰富的海洋生物蕴藏着巨大的开发潜力。海洋是人类未来的大药 房。 透 明 海 参 透 明 无 壳 海 蜗 牛 南 极 海 底 生 物 最新海洋生物普查
2.Feature of Secondary Metabolites from Marine Organism Contain Halide Lis 11,7:124-1 6
6 31 2. Feature of Secondary Metabolites Feature of Secondary Metabolites from Marine Organism u Limited Content u Structural Diversity u Stronger/Diversity Activity u Often Contain Halide and Sulfate u Unusual Metabolite Containing N O O O OH O Sesterterpenoid from Japanese Sponge Br Cl Br Br Cl Cl Halogenated Monoterpene Cl Cl Me Br Br Me Red algal 32 O AcO AcO AcO AcO I Cl O O O H O O AcO AcO AcO Cl O O O H I O Dichotellides A-E, five new iodine-containing briarane type diterpenoids from the South China Sea gorgonian Dichotella gemmacea. Liu Yonghong Tetrahedron 2011, 67 : 1245-1250 Contain Halide Contain Halide