SYNTHESIS OF PHYSIOLOGICALLY ACTIVE NATURAL PRODUCTS

生理活性天然产物的合成

• 批准号: 3179392
• 负责人: FREDERICK E ZIEGLER
• 金额: $ 17.71万
• 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/3179392
• 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.

该方案提出要进行方法和战略的研究 适用于合成一些天然产物， 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制将是 探讨了 这样一个计划的成功可以导致新的方法， 化学合成和药物设计的新入口。 丝裂霉素C目前在日本用于治疗某些 癌的 最近分离的丝裂霉素同源物FR 900482和FR 66979和合成衍生物FR 973，已经在一些实验中显示， 与丝裂霉素C相比具有上级活性的实例。 新 的形成和官能化的合成方法， 这些化合物的骨架，希望还有化合物本身， 将被探索。 其中一组要研究的化合物是二烯，霉菌 来自镰孢属物种的代谢物。 这一类的成员 化合物包括胍（抗肿瘤和真菌毒性剂），其是一种 制备T-2毒素（霉菌毒素和致病菌）的中间体 食物中毒性白细胞减少症（ATA））和FS-2（胚胎毒性剂）。 第四个目标是东莨菪碱B的合理合成， 抗病毒剂与抗病毒剂的结构密切相关， 抗有丝分裂剂，蚜虫菌素。