PALLADIUM APPROACHES TO HETEROCYCLES AND PROSTAGLANDINS

钯合成杂环化合物和前列腺素的方法

• 批准号: 3272152
• 负责人: RICHARD C. LAROCK
• 金额: $ 11.76万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3272152
• 关键词: alpha benzopyrone; antibiotics; antifungal agents; antineoplastics; benzodiazepines; benzofurans; beta lactam antibiotic; carbonyl compound; cardiovascular disorder chemotherapy; drug design /synthesis /production; furans; heterocyclic compounds; indoles; isoquinolines; lactams; lactones; mercury; palladium; prostaglandins; pyrroles; quinoline; reproductive system disorder chemotherapy; saturated /unsaturated bonds; thallium

A number of potentially important new synthetic routes to heterocyclic compounds and prostaglandins are outlined, all of which take advantage of the ease with which organopalladium compounds react with olefins or carbon monoxide to generate new carbon-carbon bonds. The immediate precursors of the organopalladium compounds are usually organomercurials and new routes to cis-vinylmercurials, acylmercurials, and a number of new functionally substituted organomercurials are proposed. The facile palladium-promoted ring-opening of cyclopropanes, cyclobutanes, epoxides, oxetanes, aziridines and Beta-lactones appears to afford new synthetic methodology applicable in the synthesis of pheromones, terpenes, and particularly nucleosides having antitumor, antimicrobial, and antiviral activity. Extensions of our newly developed, palladium-based heteroannulation approach to heterocycles are also proposed. These involve the synthesis of new reagents; the heteroannulation of simple alkenes, allylic halides, enones, siloxydienes and allenes; and extension of these reactions to simple organic halides. Potential applications in the synthesis of sesquiterpene lactones, vitamin E, and alkaloids possessing antitumor activity are outlined. The development of analogous carboannulation processes should prove valuable in the synthesis of carbocycles such as prostaglandins. New routes to unsaturated lactones, ethers, and carbocycles such as prostaglandins are also now available through intramolecular Pi-allylpalladium displacement processes. The intramolelcular cyclization of organopalladium compounds has been shown to provide new routes to butenolides and benzofurans, and these processes should prove applicable to the synthesis of lactams, coumarins, quinolones, isocoumarins, quinones, pyrones, indoles, oxindoles, isoquinolines, and the pyrrolizidine alkaloids. Finally, organopalladium additions to cyclic olefins and dienes have already provided highly efficient routes to prostaglandins of the A, E, and F series and many promising new routes to these and other prostaglandins have been uncovered. Successful completion of this work should 1) open up entirely new routes to many naturally occurring, biologically active heterocycles and prostaglandins; 2) provide a number of interesting new compounds which might show physiologicalactivity and hopefully medicinal utility; and finally 3) greatly shorten present syntheses of many vitally important heterocycles and prostaglandins.

一些潜在的重要杂环合成新路线 概述了化合物和前列腺素，所有这些都利用了 有机钯化合物与烯烃或碳反应的容易程度 一氧化碳生成新的碳-碳键。的直接前身 有机钯化合物通常是有机汞化合物和新的路线。 顺式-乙烯基汞，酰基汞，以及一些新的功能 提出了取代有机汞化合物的概念。轻而易举的钯推动了 环丙烷、环丁烷、环氧化物、氧杂环烷、氮杂环丙烷的开环 而β-内酯似乎提供了适用于 信息素信息素、萜类化合物的合成，尤其是具有 具有抗肿瘤、抗微生物和抗病毒活性。我们新推出的 已开发的基于钯的杂环合成杂环的方法是 也提出了。这些涉及新试剂的合成； 单烯烃、烯丙基卤化物、烯酮、硅氧二烯的杂环化 和联烯；以及将这些反应扩展到简单的有机卤化物。 倍半萜内酯、维生素在合成中的潜在应用 E，以及具有抗肿瘤活性的生物碱。这个 开发类似的碳环化工艺应被证明在 碳环的合成，如前列腺素。新路由至 不饱和内酯、醚和碳环，如前列腺素 现在也可以通过分子内PI-烯丙基钯置换获得 流程。有机钯化合物的分子内环化反应 已被证明为丁烯内酯和苯并呋喃提供了新的路线，以及 这些方法应该被证明适用于内酰胺类的合成， 香豆素，喹诺酮，异香豆素，对苯二酚，吡喃酮，吲哚，氧吲哚， 异喹啉和吡咯里西定生物碱。最后，有机钯 环烯烃和二烯烃的添加已经提供了很高的 A、E和F系列和许多系列前列腺素的有效途径 有希望的这些和其他前列腺素的新途径是 没有遮盖物。这项工作的成功完成应该1)完全开放 合成许多天然存在的生物活性杂环的新途径 和前列腺素；2)提供了许多有趣的新化合物 可能显示出生理活性，并有望产生药用价值； 最后，大大缩短了目前许多至关重要的合成 杂环和前列腺素。