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：
6945402
负责人：
RICHARD C. LAROCK
金额：
$ 19.42万
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/6945402
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）：绝大多数医学上重要的药物含有杂环或碳环。功能取代的炔烃的亲电环化几乎没有被研究，尽管它似乎是一种非常有前途的途径，可以得到一系列具有医学意义的、功能取代的杂环和碳环。 Larock 小组进行的初步工作表明，功能取代的炔烃的亲电环化在极其温和的反应条件下很容易提供非常高产率的各种卤素、硫和硒取代的苯并噻吩、异喹啉、苯并呋喃和异香豆素。这项工作将继续进行并扩展到各种其他环化，包括香豆素、呋喃香豆素、呋喃黄酮、吲哚、苯并硒吩、苯并内酰胺、二氢嘧啶、2-呋喃酮、2-吡咯啉酮、苯并吡喃、色酮和杂原子类似物、呋喃、噻吩、吡咯、恶唑类、异恶唑类、吡唑类、吡啶类、喹啉类、香豆素类、茚类、茚酮类、萘酚类和苯酚类。连续碘环化、Sonogashira 偶联和进一步的亲电环化似乎有望成为稠合多环杂环的有效途径。功能取代的丙二烯的类似环化似乎也很有前景。还将探索这些环化中可能使用的亲电子试剂的范围，包括有机钯化合物。随后通过钯催化过程对所得含卤素杂环和碳环的精制，为构建药学上感兴趣的化合物提供了高度、有效的方法，并将对其合成进行研究。