STUDY ON THE MICROBIAL METABOLITRES AS THE MEDICINAL RESOURCES

组织这一合作研究项目是为了从微生物的代谢物中探索药用资源，微生物是无限数量的新生物活性化合物的生产者。在本研究中，取得了以下研究成果：寻找干扰微管功能的微生物产物，分离出曲霉毒素。它们与微管蛋白的相互作用已被阐明(岩崎)。建立了一种通用的多肽化合物合成方法TS-BS。推测了多肽在生物膜和脂质双层中形成离子通道的机制。从马桶提取物中分离得到了几个具有抗肿瘤活性和谷氨酸受体活性的新化合物。测定了它们的化学结构，并研究了它们的构效关系(NOZOE)。从子囊菌代谢产物中分离得到15个新的单胺氧化酶(MAO)抑制化合物。研究了它们的结构和构效关系(Yamazaki)。用培养的中国仓鼠V79细胞证实了合成雌激素和天然雌激素对微管的破坏作用，并与其细胞毒性和生长抑制活性(Sato)相关。发现了神经发生诱导剂lactacystin和gp120-CD4结合抑制物异嗜色素I、II和WK-3419B(田中)。通过放射性标记前体(Nakagawa)的喂养实验，研究了lactacystin的生物合成途径及其立体化学方面。在1，3-多元醇聚合合成的基础上，立体选择性地合成了戊霉素多元醇段。成功地合成了杨梅酰胺A的右半部分，从而实现了杨梅酰胺的正式全合成，并成功地构建了合成片段A、B、C，并实现了这些片段的连接。

This co-operative research project was organized to explore medicinal resources from the metabolites of microorganisms which are the producers of unlimitted numbers of novel bioactive compounds. In the research therm, the following results have been accumulated.The microbial procducts that interfere with microtubule functions have been searched and ustiloxins were isolated. Their interaction with tubulin have been clarified (IWASAKI). A generic cynthetic method for peptibols, TS-Bs, was established. A ion channel formation mechanism by peptibols in biomembranes and lipid bilayrs was deduced (FUJITA). Several new compounds having antitumor activity and the activities towards glutamate receptor have been isolated from mashroom extracts. Their chemical structures were determined and the structure-activity relationships were examined (NOZOE). Fifteen new monoamine oxidase (MAO)-inhibitory compounds were isolated from the metabolites of Ascomycetes. Their structures and structure-activity relationships were studied (YAMAZAKI). Microtubule disruption by synthetic and natural estrogens were proved by Chinese hamster V79 cells in culture, and were correlated with their cytotoxicity and growth inhibitory activity (SATO). The neurogenesis inducer, lactacystin, and the gp120-CD4 binding inhibitors, isochromophilones I, II and WK-3419B were discovered (TANAKA). Biosynthetic pathway of lactacystin and its stereochemical aspect were investigated by feeding experiments of radio-labeled precursors (NAKAGAWA). Polyol segment of pentamycin was synthesized stereoselectively based on a convergent synthesis of 1,3-polyol. Synthesis of right half of mycalamide A was accomplished, which constututes a formal total synthesis of mycalamide As a total assymmetric synthesis of ISP-I, an immunosuppressive component from Isalia sinclairii, constructuion of the synthetic fragments A,B,C and connection of these fragments were succesfully achieved.