Synthesis of Medicinally Important Heterocycles

具有药用价值的杂环化合物的合成

基本信息

批准号：
6759066
负责人：
RICHARD C. LAROCK
金额：
$ 18.45万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-01 至 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6759066
关键词：
alkynes benzopyrans chemical synthesis cyclization furans furocoumarin halogens heterocyclic compounds indoles method development oxazoles pyrazoles pyrroles selenium sulfur thiophenes

项目摘要

DESCRIPTION (provided by applicant): The vast majority of medicinally important drugs contain a heterocyclic or carbocyclic ring. The electrophilic cyclization of functionally-substituted alkynes has been little studied, although it would appear to be a very promising route to an extraordinary range of medicinally interesting, functionally-substituted heterocycles and carbocycles. The Larock group has carried out preliminary work suggesting that the electrophilic cyclization of functionally-substituted alkynes readily affords very high yields of a wide variety of halogen-, sulfur- and selenium-substituted benzothiophenes, isoquinolines, benzofurans, and isocoumarins under exceptionally mild reaction conditions. This work will be continued and extended to a wide variety of additional cyclizations including coumestans, furocoumarins, furoflavones, indoles, benzoselenophenes, benzolactams, dihydropyrimidines, 2-furanones, 2-pyrrolinones, benzopyrans, chromones and heteroatom analogues, furans, thiophenes, pyrroles, oxazoles, isoxazoles, pyrazoles, pyridines, quinolines, coumarins, indenes, indenones, naphthols, and phenols. Sequential iodocyclization, Sonogashira coupling and further electrophilic cyclization appears promising as an efficient route to fused polycyclic heterocycles. Analogous cyclizations of functionally-substituted allenes also appear quite promising. The range of electrophiles, which might be employed in these cyclizations, including organopalladium compounds, will also be explored. Subsequent elaboration of the resulting halogen-containing hetero- and carbocycles via palladium-catalyzed processes provides highly, efficient methodology for the construction of pharmaceutically interesting compounds, whose synthesis will be pursued.

描述（由申请人提供）：绝大多数具有药物重要的药物包含杂环或碳环环。功能取代炔烃的亲电环化几乎没有研究，尽管它似乎是通往一系列非常有前途的一系列具有药物有趣的，功能化的杂环和carbocycles和carbocycles的途径。 Larock集团进行了初步工作，表明功能取代的炔烃的亲电环境容易地提供了多种卤素，硫 - 硫酸盐和硒溶质的苯甲甲苯，苯甲甲，等二喹啉，苯甲甲酸酯，苯并呋喃和异摩尔蛋白。 This work will be continued and extended to a wide variety of additional cyclizations including coumestans, furocoumarins, furoflavones, indoles, benzoselenophenes, benzolactams, dihydropyrimidines, 2-furanones, 2-pyrrolinones, benzopyrans, chromones and heteroatom analogues, furans, thiophenes, pyrroles, oxazoles,异恶唑，吡唑，吡啶，喹啉，香豆素，indenes，idenones，萘酚和苯酚。顺序的碘环化，Sonogashira耦合和进一步的亲电环化似乎是通往融合多环芳烃的有效途径。功能取代的艾伦（Allenes）的类似循环似乎也很有希望。还将探索在包括细胞核化合物在内的这些环化中使用的电生物的范围。随后通过钯催化的过程阐述了由此产生的含卤素的异质和碳纤维，为构建药物有趣的化合物提供了高度，有效的方法，其合成将被追求。