SYNTHESIS OF PHYSIOLOGICALLY ACTIVE NATURAL PRODUCTS

生理活性天然产物的合成

• 批准号: 3179387
• 负责人: FREDERICK E ZIEGLER
• 金额: $ 15.7万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3179387
• 关键词: Fusarium; analog; antineoplastics; antiviral agents; aphidicolin; chemical synthesis; drug design /synthesis /production; embryo /fetus toxicology; mitomycin C; mycotoxins

This program proposes to conduct studies on methods and strategies applicable to the synthesis of a number of natural products that display a range of physiological activity. In so doing, new methods of chemical synthesis and the mechanism by which these reactions occur will be explored. The success of such a program can lead to new methods of chemical synthesis and to new entries into drug design. Mitomycin C is currently used in Japan in the treatment of certain cancers. The recently isolated mitomycin congeners FR900482 and FR 66979, and the synthetic derivative FR973, have been shown in some instances to have superior activity compared to mitomycin C. New synthetic approaches to the formation and functionalization of the skeleton of these compounds, and hopefully the compounds themselves, will be explored. One group of compounds to be studied is the trichothecenes, mold metabolites derived from Fusarium species. Members of this class of compounds include anguidine (antitumor and mycotoxic agent), which is an intermediate in the preparation of T-2 toxin (mycotoxin and causative agent of alimentary toxic aleukia (ATA)), and FS-2 (embryotoxic agent). The fourth objective is the rational synthesis of scopadulcic acid B, an antiviral agent closely related to the structure of the antiviral and antimitotic agent, aphidicolin.

该计划提出了开展方法和策略的研究 适用于多种天然产物的合成展示 一系列生理活动。在此过程中，新的化学方法 合成和这些反应发生的机理将是 探索过了。这样一个项目的成功可以带来新的方法 化学合成和药物设计的新条目。 丝裂霉素C目前在日本用于治疗某些 癌症。新分离的丝裂霉素同系物FR900482和FR 66979，以及合成衍生物FR973，已经在一些 与丝裂霉素C相比具有更好活性的实例 形成和功能化的综合方法 这些化合物的骨架，希望还有化合物本身， 将会被探索。 一组要研究的化合物是三氯乙烯，霉菌 从镰刀菌物种中提取的代谢物。这一类的成员 化合物包括安定丁(抗肿瘤和真菌毒剂)，它是一种 T-2毒素制备的中间体(霉菌毒素和致病因子 消化道毒性阿魏酸菌剂(ATA)和FS-2(胚胎毒性药剂)。 第四个目标是合理地合成菊花酸B，和 抗病毒药物与结构密切相关的抗病毒和 抗有丝分裂药，APHIDICOIN。