Synthesis of Medicinally Important Heterocycles

具有药用价值的杂环化合物的合成

• 批准号: 7121537
• 负责人: RICHARD C. LAROCK
• 金额: $ 18.95万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 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/7121537
• 关键词: alkynes; benzopyrans; chemical synthesis; cyclization; furans; furocoumarin; halogens; heterocyclic compounds; indoles; method development; oxazoles; pyrazoles; pyrroles; selenium; sulfur; thiophenes

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）：绝大多数重要的药用药物含有杂环或碳环。功能取代炔的亲电环化研究很少，尽管它似乎是一条非常有前途的途径，可以得到一系列非常有趣的医学上的功能取代杂环和碳环。Larock小组已经进行了初步的工作，表明在异常温和的反应条件下，功能取代炔的亲电环化很容易提供各种卤素、硫和硒取代的苯并噻吩、异喹啉、苯并呋喃和异香豆素的高收率。这项工作将继续并扩展到各种各样的其他环化，包括coumestans、呋喃香豆素、呋喃黄酮、吲哚、苯并硒苯、苯内酰胺、二氢嘧啶、2-呋喃酮、2-吡咯啉酮、苯并吡喃、铬酮和杂原子类似物、呋喃、噻吩、吡咯、恶唑、异恶唑、吡唑、吡啶、喹啉、香豆素、茚、茚酮、萘酚和酚。序碘环化、Sonogashira偶联和进一步的亲电环化是制备融合多环杂环的有效途径。类似的功能取代烯的环化反应也很有前景。还将探讨可能用于这些环化反应的亲电试剂的范围，包括有机钯化合物。随后通过钯催化工艺对所得到的含卤杂环和碳环进行精化，为构建药学上感兴趣的化合物提供了高效的方法，这些化合物的合成将继续进行。