TOTAL SYNTHESIS OF MYCOTOXINS AND RELATED COMPOUNDS

霉菌毒素及相关化合物的全合成

• 批准号: 3289455
• 负责人: JIN K CHA
• 金额: $ 13.55万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3289455
• 关键词: O glycosidase; antineoplastics; antiviral agents; carbohydrates; carcinogenesis; chemical structure function; drug design /synthesis /production; drug screening /evaluation; enzyme inhibitors; forskolin; mycotoxins; oxidative phosphorylation; stereochemistry

The proposed program is directed at the total synthesis of a wide range of biologically active mycotoxins and structurally related compounds. The synthetic strategies are chosen to provide efficient enantio- and stereoselective entries to target compounds. Our objective is to develop efficient synthetic methods which would allow the preparation of natural products and their various synthetic derivatives in significant quantities for biological testing. Specific target molecules include polyhydroxy indolizidine alkaloids, which act as potent glycosidase inhibitors; several Dendrobatid alkaloids, which provide invaluable tools for the investigation of ion transport in many biological systems; polyene mycotoxins of the citreoviridin family, which are potent inhibitors of oxidative phosphorylation; forskolin, which has been shown to activate adenylate cyclase and display a wide range of physiological effects; the seco acid of erythronolide A, and prostanoids. In particular, members of alkaloidal glycosidase inhibitors (i.e., swainsonine and castanospermine) are believed to be promising leads for the development of anticancer and antiviral agents. We anticipate that synthetic projects of verrucosidin and citreoviridin, which were initiated during the first three years of this grant, will be largely completed by the July 1, 1989 starting date requested in this application. This pivotal synthetic methodology to be utilized involves efficient stereoselection of prochiral sp2 sites by an allylic oxygen substituent. We believe a firm foundation has been laid for its application to natural product synthesis.

提出的程序针对广泛范围的总合成 生物活性的霉菌毒素和结构相关的化合物的。 选择合成策略以提供有效的对照和 立体选择性条目到目标化合物。 我们的目标是发展 有效的合成方法，可以制备自然 产物及其各种合成衍生物 生物测试的数量。 特定的靶标分子包括多羟基吲哚嗪生物碱， 充当有效的糖苷酶抑制剂；几个树突状 生物碱，为离子研究提供了宝贵的工具 在许多生物系统中运输；多烯霉菌毒素 citreoviridin家族，它们是有效的氧化抑制剂 磷酸化； Forskolin，已证明可以激活腺苷酸盐 循环酶并表现出广泛的生理作用； seco酸 erythronolide a和前列腺素。 特别是 生物碱糖苷酶抑制剂（即瑞氏蛋白和castanospermine） 据信抗癌和 抗病毒药。 我们预计Verrucosidin的合成项目 和citreoviridin，是在前三年开始的 这笔赠款将在1989年7月1日开始日期之前完成 在此应用程序中要求。 这种要使用的关键合成方法涉及有效 通过烯丙基氧取代基对体手术SP2位点的立体选择。 我们认为，牢固的基础是因为其适用于自然的基础 产品合成。