COMPREHENSIVE RESEARCH TOWARD THE ELUCIDATION OF BIOLOGICAL ACTIVITIES OF NATURAL ORGANIC COMPOUNDS

1. 具有双醛功能的萜类化合物所表现出的结构和生物活性的广泛多样性引起了人们对其合成的极大兴趣。我们对多功能型环烯醚萜类化合物和与环烯醚萜类化合物结构相关的海洋二萜和酯萜类化合物特别感兴趣，因为这些萜类化合物具有细胞毒性、抗白血病、抗菌、抗真菌、抗病毒和抗炎活性。本课题完成了从海藻中分离得到的一种新型10 -杂芳香二萜halitunal的合成。2. 已经从红藻中分离出许多具有直c15链骨架的海洋环溴醚。首次以月桂醇为原料合成了该类具有代表性的天然产物月桂醇。3. 完成了雪卡毒素和甘比亚毒素AB环片段的立体选择性合成，并确定了C2的绝对构型。白蛋白偶联物抗雪卡毒素抗体等。4. 从皂鱼的防御性黏液皮肤分泌物中分离出一种亲脂性鱼毒素，命名为lipo- grammistin -A，并对其进行了化学表征。Lipogrammistin-A是在动物王国中发现的第一个大环多胺内酰胺。5. 合成了从蕨类植物中分离得到的最终致癌物Ptaquilosin。并对该化合物的DNA裂解机理进行了分析。摘要合成了一种有效的抗肿瘤大环内酯类化合物——黑金槟榔素。从海参黑木耳中合成了一种有效的细胞毒性环沉积肽Doliculide。6. 巯基糖苷类化合物既可以作为保护基团，又可以通过适当的亲硫试剂活化成为有效的糖基供体，已广泛应用于复杂碳水化合物的合成。本研究开发了两种新的巯基苷糖基化反应，并成功地应用于糖脂的合成。少

1. The broad diversity of both structure and biological activity exhibited by terpenoids having dialdehyde functionality has generated much interest for their synthesis. We were especially attracted to the polyfunctional iridoids and marine di- and sester terpenoids structurally related to the iridoid since these terpenoids exhibit cytotoxic, antileukemic, antimicrobial, antifungal, antiviral and anti-inframmatory activities. In this project we acoomplished the synthesis of halitunal, a novel 10 pi-heteroaromatic diterpene isolated from marine algae Halimeda tuna. 2. A number of marine cyclic bromo-ethers having straight C15-chained skeletones have benn isolated from red algae. First synthesis of laurencin, a representative natural product of this class, was accomplished from laurediol. 3. Stereoselective synthesis of AB ring fragments of ciguatoxin and gambiertoxin was accomplished and the absolute configuration of C2 was determined. Albumin conjugates for anti-ciguatoxin antibody, wa … More s also synthesized. 4. A lipophilic ichthyotoxin from the defensive mucous skin secretion of soapfish, named lipo-grmmistin-A was isolated and chemically characterized. Lipogrammistin-A is the first example of a macrocyclic polyamine lactam found in the animal kingdam. 5. Ptaquilosin, the final carcinogenic substance isolated from bracken fern was synthesized. The mechanism of DNA cleavage of this compound was elucidated. Aplyronine, a potent antitumor macrolide from the sea hare Aplysia kurodai was synthesized. Doliculide a potent cytotoxic cyclodepsipeptide from sea hare Dolabella auricularia was also synthesized. 6. Thioglycosides, which can be used as the protecting group at the anomeric position but can be used as efficient glycosyl donors through activation with appropriate thiophilic reagents, have been widely used for the synthesis of complex carbohydrates. In the present study two novel glycosylation reaction using thioglycosides were developed and successfully applied for the synthesis of glycolipids. Less