TRICHOTHECANES, AMINO SUGARS, AND AVERMECTINS

单端孢菌素、氨基糖和阿维菌素

• 批准号: 3281545
• 负责人: Bertram Oliver Fraser-Reid
• 金额: $ 17.42万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281545
• 关键词: aminosugar; anthelmintics; antibiotics; chemical elimination; chemical structure; drug design /synthesis /production; glucose; stereoisomer

This research program is concerned with three different classes of compounds, tricothecanes, amino sugars and the avermectins. During the first grant period work on the trichothecanes has been highly productive particularly with regard to the macrocyclic systems. We have made significant progress towards verrucarol and we are now in a position to explore a number of optional routes from D-glucose which will not only give the trichothecanes in optically active form, but will allow the preparation of several modified systems. The first grant period on the amino sugars has also been highly successful having lead to syntheses of garosamine, holocosamine, sibirosamine, ristosamine and daunosamine. Highly significant methodologies have been developed using allylic substrates which promise to trivialize the stereocontrolled formation of cis-hydroxy amine systems. In the forthcoming grant period we will strike out to investigate homoallylic systems, and a particularly appealing route to thienamycin has been conceived along these lines. Research on the third class of compounds, the avermectins, will be initiated in the forthcoming grant period. The main challenge here is seen to be the preparation of an oxa-hydrindane system which may be prone to self-destruction by way of two Beta-eliminations. We will investigate the use of carbohydrate systems not only to provide the oxa-hydrindane in optically active form, but also to prevent the impending self destruction. All components of the avermectins are to be prepared from readily available sugar derivatives. All three classes of compounds are of immense current biological interest as anti-tumor agents, antibiotics or anti-helminthic agents.

该研究计划涉及三种不同类型的 化合物、三氯氧烷、氨基糖和阿维菌素。 期间 在第一个赠款期内，关于非洲裔美国人的工作富有成效。 特别是对于大环体系。 我们取得了 在verrucarol方面取得了重大进展，我们现在能够 从D-葡萄糖中探索一些可选的途径， 以光学活性形式存在的二硫代环己烷，但将允许制备 几个改进的系统。 氨基糖的第一个授权期 也非常成功地导致了加洛胺的合成， 全糖胺、西比糖胺、瑞斯托糖胺和柔红霉素胺。 高度 已经开发了使用烯丙基底物的重要方法 其承诺使顺式-羟基的立体控制形成变得平凡， 胺体系 在即将到来的资助期内，我们将致力于 研究高烯丙基体系，以及一种特别吸引人的途径， thienamycin已经沿着这些路线被构思。 研究第三 一类化合物，阿维菌素，将开始在即将举行的 补助期。 这里的主要挑战被认为是准备一个 氧杂-茚满体系，其可能倾向于通过两个 淘汰赛 我们将研究碳水化合物系统的使用， 不仅提供光学活性形式的氧杂-茚满，而且还 阻止即将到来的自我毁灭 阿维菌素的所有组分 由容易获得的糖衍生物制备。 所有三 化合物的种类是目前生物学上的巨大兴趣， 抗肿瘤剂、抗生素或抗蠕虫剂。