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

1.具有双醛官能团的萜类化合物具有广泛的结构和生物活性，引起了人们对其合成的极大兴趣。尤其是与环烯醚衍生物结构相关的多功能环烯醚衍生物和海洋二、七萜类化合物，因为这些萜类化合物具有细胞毒性、抗白血病、抗微生物、抗真菌、抗病毒和抗基础设施等活性。在本项目中，我们完成了从金枪鱼海藻中分离出的一种新的10-pi-杂芳烃二萜--Halitunal的合成。2.从红藻中分离到许多具有直C15链骨架的海洋环状溴醚化合物。以月桂二醇为原料首次合成了这类具有代表性的天然产物劳伦辛。3.完成了雪卡毒素和冈比亚毒素AB环片段的立体选择性合成，确定了C2的绝对构型。抗雪卡毒素抗体白蛋白结合物Wa…更多的S也合成了。4.从肥皂鱼防御性粘液皮肤分泌物中分离到一种亲脂性鱼毒素，命名为Lipo-grmmistin-A。脂质-A是在动物王国中发现的第一个大环多胺内酰胺的例子。5.合成了从蕨类植物中分离得到的最终致癌物质Ptaquilosin。并对该化合物的DNA切割机理进行了初步探讨。从海兔黑线海兔中合成了一种有效的抗肿瘤大环内酯类化合物--阿普利罗宁。合成了一种从海兔耳廓中提取的具有细胞毒性的环磷脂多肽。6.硫代糖苷类化合物可以作为异构体上的保护基团，也可以通过适当的亲硫试剂活化，作为高效的糖基供体，被广泛用于合成复杂的碳水化合物。本研究开发了两种新的基于硫代糖苷的糖基化反应，并成功地应用于糖脂的合成。较少

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