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.

拟议的计划旨在全面综合各种 生物活性霉菌毒素和结构相关化合物。 选择合成策略以提供有效的对映体和 目标化合物的立体选择性条目。 我们的目标是发展 有效的合成方法可以制备天然的 产品及其各种合成衍生物具有重要意义 用于生物测试的数量。 具体的靶分子包括多羟基吲哚里西啶生物碱， 作为有效的糖苷酶抑制剂；几只石杷虫 生物碱，为研究离子提供了宝贵的工具 许多生物系统中的运输；多烯真菌毒素 黄绿绿素家族，是氧化酶的有效抑制剂 磷酸化；毛喉素，已被证明可以激活腺苷酸 环化酶并表现出广泛的生理效应；断链酸 erythronolide A 和前列腺素类。 特别是，成员 生物碱糖苷酶抑制剂（即苦马豆素和栗精胺） 被认为是抗癌药物开发的有前景的线索 抗病毒剂。 我们预计verrucosidin的合成项目 和黄绿素，这是在前三年启动的 这笔赠款将在 1989 年 7 月 1 日开始日期前大部分完成 本申请中要求。 这种要利用的关键合成方法涉及高效 通过烯丙基氧取代基对前手性 sp2 位点进行立体选择。 我们相信已经为其在自然领域的应用奠定了坚实的基础 产品合成。