New Methods for Nitrogen and Oxygen Heterocycle Synthesis
氮氧杂环合成新方法
基本信息
- 批准号:10430185
- 负责人:
- 金额:$ 33.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AerobicAlcoholsAlkenesAminesBiochemicalBiochemical ProcessBiological AvailabilityBiologyBiomedical ResearchCarbonCarboxylic AcidsCardiovascular DiseasesCatalysisChemicalsChemistryCommunicable DiseasesCopperCouplingCyclizationDevelopmentDiabetes MellitusDrug IndustryEngineeringEthersGoalsHumanHydrogenationIn SituKnowledgeLigandsMalignant NeoplasmsMapsMental HealthMethodologyMethodsMolecularNatural ProductsNeurodegenerative DisordersNitrogenOrganic SynthesisOxidantsOxidasesOxygenOxygenasesPharmaceutical PreparationsPharmacologic SubstanceProcessProductionPyrrolidinesReactionReagentResearchResourcesStereoisomerStructureStyrenesTechnologyTestingTimeWorkbioactive natural productsdensitydienedrug developmentdrug discoveryenantiomerexperimental analysishuman diseaseinventionketallarge scale productionmethod developmentoxidationprogramssmall moleculetetrahydrofurantheoriestoolwasting
项目摘要
Project Summary/Abstract
The efficient production of small organic molecules and chemical processes impacts pharmaceutical research,
both drug discovery and process chemistry. Chiral compounds make up a substantial portion of bioactive small
organic molecules. Their enantioselective synthesis minimizes use of chiral separation technology, which can
be time and resource intensive, and the production of undesired enantiomers, which are often considered
chemical waste. New copper-catalyzed alkene difunctionalization reactions that enable efficient and
stereoselective synthesis of chiral amine derivatives and ethers, including saturated heterocycles, are being
developed. The products of these reactions readily map on to structures contained in bioactive organic small
molecules such as natural products and pharmaceuticals. In Aim 1, enantioselective aerobic copper-catalyzed
alkene oxidative difunctionalizations will be explored for the direct synthesis of 2-formyl pyrrolidines and 2-formyl
tetrahydrofurans. Application of these aerobic cyclizations to the streamlined synthesis of bioactive natural
products and small molecule intermediates useful to drug discovery will test the practical utility of the methods.
The focus of Aim 2 is the development of methods for the enantioselective synthesis of chiral bridged bicyclic
ketals and other saturated heterocycles that contain fully substituted carbon stereocenters. A number of these
transformations are enabled by a radical group transfer strategy. Mechanistic aspects of these reactions will be
explored, which will enable their rational optimization and predictable application. The focus of Aim 3 is on the
development of copper-catalyzed 2- and 3-component reactions that involve the coupling of alcohol and amine
derivatives with styrenes or dienes, and alkyl radicals formed in situ. Mechanistic aspects of these reactions,
especially related to stereoselectivity, will be investigated. Development of these chemical transformations will
enable their use in multi-step organic synthesis in drug discovery and chemical biology applications. Their
invention enables new options for synthetic organic chemists, which may enable diverse small molecule
candidates to be synthesized efficiently. Lessons learned in reaction engineering for efficiency and selectivity
will be applicable to the invention and development of related useful chemical processes.
项目总结/摘要
有机小分子和化学过程的有效生产影响了药物研究,
药物发现和工艺化学。手性化合物构成了生物活性小分子的相当大的一部分,
有机分子它们的对映选择性合成最大限度地减少了手性分离技术的使用,
是时间和资源密集型的,并且产生不希望的对映异构体,这通常被认为是
化学废物。新的铜催化的烯烃双官能化反应,
手性胺衍生物和醚,包括饱和杂环的立体选择性合成正在进行,
开发这些反应的产物很容易映射到生物活性有机小分子中所含的结构上。
分子,如天然产物和药物。在目标1中,对映选择性好氧铜催化
将探索烯烃氧化双官能化以直接合成2-甲酰基吡咯烷和2-甲酰基吡咯烷。
四氢呋喃。这些有氧环化反应在生物活性天然产物的流线型合成中的应用
用于药物发现的产物和小分子中间体将测试该方法的实际效用。
目标2的重点是发展手性桥连双环的对映选择性合成方法
缩酮和其它含有完全取代的碳立构中心的饱和杂环。其中一些
通过基团转移策略实现转化。这些反应的机理方面将是
探索,这将使他们的合理优化和可预测的应用。目标3的重点是
铜催化的涉及醇和胺偶联的2-和3-组分反应的开发
具有苯乙烯或二烯的衍生物和原位形成的烷基。这些反应的机理方面,
特别是与立体选择性有关的问题。这些化学转化的发展将
使它们能够用于药物发现和化学生物学应用中的多步有机合成。他们的
本发明为合成有机化学家提供了新的选择,
候选人必须有效地合成。从反应工程中获得的效率和选择性经验教训
将适用于相关有用化学工艺的发明和开发。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Sherry R Chemler其他文献
Sherry R Chemler的其他文献
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{{ truncateString('Sherry R Chemler', 18)}}的其他基金
Administrative Equipment Supplement for New Methods for Nitrogen and Oxygen Heterocycle Synthesis
氮氧杂环合成新方法管理设备补充
- 批准号:
10380459 - 财政年份:2006
- 资助金额:
$ 33.27万 - 项目类别:
New Methods for Nitrogen and Oxygen Heterocycle Synthesis
氮氧杂环合成新方法
- 批准号:
10207659 - 财政年份:2006
- 资助金额:
$ 33.27万 - 项目类别:
New Methods for Nitrogen and Oxygen Heterocycle Synthesis
氮氧杂环合成新方法
- 批准号:
9143146 - 财政年份:2006
- 资助金额:
$ 33.27万 - 项目类别:
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