腔肠动物一水母 水母是一种低等的斯动物在分类学上康干腔对 书缺有异移中 箱水母 腔肠动物一海葵 4.软体动物Molluses ire of secre 光放赛康【物四本李分精转本，宫 4.软体动物Molluscs 软体动物Molluses and the s of thi 长 1 子R8 hoCinandmwanA 工Wd上3K线ent 1
1 151 腔肠动物—水母 水母是一种低等的腔肠动物，在分类学上隶属于腔肠动 物门、钵水母纲。水母的种类很多，全世界大约有250种左 右，直径从10厘米到100厘米之间，常见于各地的海洋中。 箱水母 152 荷包蛋（地中海）水母 BREEDE河水母 南极洲Diplulmaris水母 葡萄牙僧帽水母 花笠水母 自海刺水母 Crossota sp水母 警报水母 白点水母 最美水母 153 腔肠动物—海葵 岩沙海葵毒素（palytoxin，PTX）亦称沙海葵毒素或群体海葵毒素。它 是从海葵Zoantharia类的Palythoa属腔肠动物中分离出来的一种毒素， 154 4. 软体动物 Molluscs Molluscs What is a sea hare? Sea hares are shell-less marine mollusks that use a complex repertoire of secreted chemicals to defend themselves against a variety of predators and to communicate with each other. 155 4. 软体动物 Molluscs Molluscs • They have long been of interest to chemists because some Sea hares consume algae that are rich in small molecules, which they concentrate and then store. The effects of this accumulation are unclear; some sea hares make use of these potentially toxic compounds by coopting the algal defenses as their own. • Terpenoids • Peptides：芋螺毒素 (Conotoxins) • Polyether 行兔 156 Sesquiterpenes 1-3 were isolated from sea hare A. dactylomela (Canary Islands). T. Dias, et al. J. Nat. Prod., 2005, 68, 1677. 软体动物 Molluscs Molluscs R Br AcO 2 R = H 3 R = Cl Br 1 Cl Br
5.被素类动物Tunicates(Ascidian) Ritterazine A arC 6.苔藓虫类Bryozoans 6.苔藓虫类Byoz0ans "rd 3irr 7.棘皮动物Echinoderms 7.棘皮动物Echinoderms
2 157 5.被囊类动物 Tunicates (Ascidian) Tunicates also called Ascidian-海鞘动物 Amino-derived Metabolite Et-743 是1972年从加勒比海红树海鞘 Ecterinascidia turbinata 抗肿瘤成分。 N NH N S O O H3C O O H3C H H OH HO CH3 O O O HO O H3C H3C CH3 H 158 Ritterazine A S. Fukuzawa, S. Matsunaga, N. Fusetani. Ritterazine A, a Highly Cytotoxic Dimeric Steroidal Alkaloid, from the Tunicate Ritterella tokiokal J. Org. Chem. 1994, 59, 6164-6166. Nobuhiro Fusetani. Ten More Ritterazines, Cytotoxic Steroidal Alkaloids from the Tunicate Ritterella tokioka. Tetrahedron 1995, 51(24). 6707-6716. P388 murine leukemia cells with IC50 values of 0.018 ng/mL. N N O O O O OH H H O H H HO HO OH H H H OH 159 6. 苔藓虫类 Bryozoans • Alkaloids & Macrolides 海洋苔藓动物俗称苔藓虫，约4000多种， 做常见的是总合草苔虫。 总合草苔虫在世界水域分布广泛， 我国沿海从渤海到南海的西沙群岛的 多盐水域都有。呈红褐色或紫褐色草丛状，4-15 cm. 1968 年亚利桑那州立大学Petti 小组发现总合草苔虫的抗癌活性。1982 年分得 Bryostani 1. O O O O O H3CO O OH H OH HO O O OCH3 O OH O O H H H H H Bryostani 1 160 6. 苔藓虫类 Bryozoans • Four alkaloids, Myriaporones 1–4 arepolyketide-derived metabolites from the bryozoan Myriapora in 2007. • There have been no reports of new bryozoan chemistry in 2004-2006. JF. Cheng, JS. Lee, R. Sakai, EA. Jares-Erijman, MV. Silva and KL. Rinehart, J. Nat. Prod., 2007, 70, 332. OAc O O O OH OH OH OAc OH O 1 2 O O OH O O OH OH 3 O OH HO O O OH OH 4 HO O 161 7. 棘皮动物 Echinoderms Echinoderms 162 7. 棘皮动物 Echinoderms Echinoderms • 海参 sea cucumbers 500 余种，100 Triterpene Saponins • 海星 sea stars 1500 种, 400 Steroid Saponins (Asterosaponins) Iorizzi M. Starfish Saponins 55. J. Nat. Prod. 1998, 61: 1319. Kitagawa I. Saponin and Sapogenol XXVI. Chem. Pharm. Bull. 1978, 26: 1864 O O OH OH HO OH OH OH HO OH H H starfish
Metabolites from Echinoderms 棘皮动物Echinoderms ◆辣终望会奢类体电春作为修门体内的常见惠水。盖 ◆L建酸化电普sterosaponins) &.细菌和真菌Bacteria&Fungi Each drop of water taken from the ocean will contai 极增徽生物(extreme mic gm,也叫徽极限环境徽 vere modestly antifungal 、高正等能够生存的撒生物。 海洋微生物是重要药用资源 应能力强：能适应各种特殊环境： 的真正生产者。 3
3 163 Physiologically active saponins have been studied extensively from sea stars and sea cucumbers, but not so useful as drugs because of their tendency to cause celllysis. Even then, glycosylated ceramides and saponins continue to be the major classes of metabolites identified in echinoderms (棘皮 动物). Metabolites from Echinoderms 164 u 棘皮动物会产生甾体皂苷作为他们体内的常见毒素，甾 体皂苷主要有4类： u 1. 硫酸化皂苷 (Asterosaponins) u 2. 环甾体皂苷 u 3. 多羟基化甾体皂元和皂苷 u 4. 新型皂苷 棘皮动物 Echinoderms Echinoderms Echinoderms are a well documented source of biologically active saponins and glycolipids 165 Two b-D-xylosides, Minutosides A 1 and B 2, were reported from the starfish Anasterias minuta (Patagonia). Minutoside B bears an unusual amidohypotaurine sidechain. Both of them were modestly antifungal. H. D. Chludil and M. S. Maier, J. Nat. Prod., 2005, 68, 1279 OH OH NaO3SO OH H H N H OH OH O OH H H O O OH HO HO O SO3Na O HO OH HO 1 2 166 • Each drop of water taken from the ocean will contain microbial species unknown to humans in a 9:1 ratio. Of more than 1.5 million microorganisms, 72000 was found in land, only ca 2000 marine microorganisms were investigated. 8. 细菌和真菌 Bacteria & Fungi Bacteria & Fungi 极端微生物(extreme microorganism) , 也叫做极限环境微 生物, 是指那些一般生物不能生存的条件下(如极酸、极碱、 极热、极冷、高盐、高压等) 能够生存的微生物。 167 William Fenical 168 种类繁多:约150 万多种； 繁殖速度快：可实现大规模生产，解决药源问题； 适应能力强：能适应各种特殊环境； 可持续性发展：不会导致物种减少和环境破坏； 可与动植物互惠共生： 可能是海洋动植物活性物质 的真正生产者。 海洋微生物是重要药用资源
海洋微生物资源丰富 Molecules Derived from the Extremes of Life 在其 Bacteria Fungi have proy A 拉” 上产建的大乐内类化合 New Tools for Drug Discovery 六、海洋天然产物的化合物类型 点 多能 物 大环内前列素 4
4 169 热液喷溢口周围存在许多长柱状、短柱状的“黑烟囱”，在其周围活跃着 一个崭新的生物群落—热水生物，构成了繁荣的深海生物圈；其生物多样性 和密度可与热带雨林相媲美。目前新发现的生物种类已经达到了10个门类 500多个种属，其中最重要的是微生物。海洋微生物是发现药物先导结构的 重要资源. 海洋微生物资源丰富 170 Molecules Derived from the Extremes of Life 171 Petrobactin sulfonate was isolated from the oil-degrading marine bacterium Marinobacter hydrocarbonoclasticus, and is the first marine siderophore containing a sulfonated 3,4-dihydroxy aromatic ring. R. J. Bergeron, G. Huang, R. E. Smith, N. Bharti, J. S. McManis and A. Butler, Tetrahedron, 2003, 59, 2007. 172 Bacteria & Fungi Bacteria & Fungi N Br Br Br Br Br OH H Macrolactin A Antiviral activity A highly brominated pyrrole antibiotic 1. 富含卤素。 2. 产生结构特殊的大环内酯类化合物。 To date, only about 300 new compounds have been isolated from the marine fungi. Marine fungi have proven to be a rich and promising source of novel anticancer, antibacterial, antiplasmodial, anti-inflammatory and antiviral agents. O CH3 O OH HO HO 173 u Exploration of new locations, collection of organisms never before sampled, and identification of chemicals with pharmaceutical potential. u New and improved platforms (such as autonomous, remote, and human occupied underwater vehicles) to take us farther and deeper are in development. u Tools and sensors that have been developed both for space exploration and for diagnostic medicine New Tools for Drug Discovery 174 前列腺素 前列腺素 胍胺类 胍胺类 聚聚醚醚 大环内酯 大环内酯 甾体、萜类、 酰胺类、酚类 皂苷等 甾体、萜类、 酰胺类、酚类 皂苷等 生物碱 生物碱 多糖多糖 肽类肽类 其他 （脂肪酸、糖脂、 吲哚类等） 其他 （脂肪酸、糖脂、 吲哚类等） 主要种类 六、海洋天然产物的化合物类型
小结 Summary History has now proven that Marine Organisms, especially Invertebrates such as sponges,soft corals, molluscs,and microorganism,produce many secondary metabolites which are unprecedented within the terrestrial biosphere. Ocean harbours the largest biodiversity in terms of different species.More and more drugs will come from Marine Natural Products. Major Marine Natural Produets will be introduced in detail in the next section 175 5
5 175 小 结 Summary Summary History has now proven that Marine Organisms, especially Invertebrates such as sponges, soft corals, molluscs, and microorganism, produce many secondary metabolites which are unprecedented within the terrestrial biosphere. Ocean harbours the largest biodiversity in terms of different species. More and more drugs will come from Marine Natural Products. Major Marine Natural Products will be introduced in detail in the next section