Heterocyclic /Carbocyclic Libraries for High Throughput

高通量杂环/碳环文库

• 批准号: 7193848
• 负责人: RICHARD C. LAROCK
• 金额: $ 34.31万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7193848
• 关键词: NIH Roadmap Initiative tag; biomedical resource; chemical models; chemical registry /resource; chemical structure; chemical structure function; chemical synthesis; combinatorial chemistry; computer simulation; heterocyclic compounds; high throughput technology; molecular dynamics; physical separation; racemization; small molecule

DESCRIPTION (provided by applicant): The Larock group at Iowa State University will prepare for high throughput screening a large number of libraries of heterocycles and carbocycles expected to exhibit a wide range of biological activity. Three very general synthetic methods primarily developed in the Larock group will be employed. (1) The Pd-catalyzed annulation of alkynes, dienes, alkenes and arynes will be employed to prepare specially diverse libraries of indoles, benzofurans, benzopyrans, coumarins, isocoumarins, phthalides, pyrones, 2-quinolones, pyridines, isoquinolin-1-ones, isoindolin-1-ones, isoquinolines, carbolines, isoindolo[2,1-a]indoles, carbazoles, dibenzofurans and various other heterocycles, plus indenones, indenes, fluoren-9-ones and 9-alkylidene-9Hfluorenes. (2) The cyclization of readily available, functionally-substituted alkynes by halogen, sulfur, selenium and organopalladium electrophiles will be utilized to prepare libraries of medicinally interesting indoles, benzofurans, coumestans, chromones, benzothiophenes, benzoselenophenes, phthalides, isocoumarins, isochromenes, isoquinolines, quinolines, furans, isoxazoles and various spirotrienones. (3) Aryne annulations will be used to prepare xanthones, thioxanthones and acridones. Halogen-containing heterocycles and carbocycles will be further elaborated to more diverse libraries by well known, Pd-catalyzed processes. This methodology is very efficient, tolerates virtually all important organic functional groups, proceeds under mild reaction conditions, affords high yields of very pure compounds, and uses readily available starting materials, reagents and catalysts. Libraries consisting of (20-100 novel, small, densely functionalized, specially diverse compounds will be prepared by this very versatile solution and solid phase chemistry already worked out in the Larock group. Racemic mixtures will be separated by the Armstrong group in Texas and molecular modeling will be carried out by the Lushington group at Kansas University. The resulting libraries will be purified to generally >95% purity using standard laboratory techniques and, if necessary, the high throughput purification techniques available to the PI through the Kansas University Center of Excellence in Chemical Methodologies and Library Development. This methodology will be widely published and the resulting libraries donated to the NIH Molecular Libraries Small-Molecule Repository and the Molecular Libraries Screening Center Network.

描述（由申请人提供）：爱荷华州立大学的Larock小组将为高吞吐量筛查做准备，以筛选大量的杂环和carbocycles图书馆，预计将表现出广泛的生物学活性。将采用三种主要在Larock组中开发的非常通用的合成方法。 (1) The Pd-catalyzed annulation of alkynes, dienes, alkenes and arynes will be employed to prepare specially diverse libraries of indoles, benzofurans, benzopyrans, coumarins, isocoumarins, phthalides, pyrones, 2-quinolones, pyridines, isoquinolin-1-ones, isoindolin-1-ones,等喹啉，碳水化合物，异丁氏菌[2,1-A]吲哚，卡唑，Dibenzofurans和其他各种杂环，以及indenones，indenones，indenes，Fluoren-9-ones和9-烷基二烯-9hhfluorenes。 （2）将利用卤素，硫，硒和有机丙达旦电力的易于获得的，功能化拟合的藻类的环化，以准备医学上有趣的吲哚库的库，苯并鸡，香豆，铬酮，铬酮，苯甲甲，苯佐糖，苯并素，苯甲酸酯，苯甲酸酯，苯甲酸酯剂，苯甲酸酯，苯甲酸酯剂，苯丙烯蛋白酶，含磷脂，等喹啉，喹啉，呋喃，依氧唑和各种螺旋烯酮。 （3）Aryne Annulation将用于制备Xanthone，Thioxanthone和Acridones。富含卤素的杂环和碳环环将通过众所周知的PD催化过程进一步阐述更多样化的文库。该方法非常有效，几乎可以容忍所有重要的有机官能团，在轻度反应条件下进行进行，可提供非常纯净化合物的高收益，并使用易于获得的起始材料，试剂和催化剂。 Libraries consisting of (20-100 novel, small, densely functionalized, specially diverse compounds will be prepared by this very versatile solution and solid phase chemistry already worked out in the Larock group. Racemic mixtures will be separated by the Armstrong group in Texas and molecular modeling will be carried out by the Lushington group at Kansas University. The resulting libraries will be purified to generally >95% purity using standard laboratory在必要时，将通过堪萨斯大学化学方法和图书馆开发的卓越中心可为PI提供高吞吐量的纯化技术，并将广泛发表。