Au/Pt Catalysis in the Synthesis of Elaborate N-Heterocycles: Methodology Develop
Au/Pt 催化合成精细 N-杂环化合物:方法开发
基本信息
- 批准号:8538430
- 负责人:
- 金额:$ 25.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-30 至 2015-02-28
- 项目状态:已结题
- 来源:
- 关键词:AlcoholsAlkaloidsAlkenesAlkynesAttentionBiologicalBiological FactorsCarbonCatalysisChemistryComplexDNA Sequence RearrangementDevelopmentDistalGoalsGoldHealth PersonnelIminesIndolesIndolizinesIndustryLaboratory ResearchLactamsLeadMetalsMethodologyMethodsOrganic ChemistryOxazolesPatternPharmaceutical PreparationsPharmacologic SubstancePharmacy (field)PreparationPublicationsPyrrolesPyrrolidinonesReactionResearchSaltsSchemeSkeletonStructureSystemanalogaziridinomitosenebasecancer therapycarbonyl groupcatalystcostcyclopentanonedesigndrug discoveryindolinemitosenenanoparticlenitronenovelpropadieneprotonationpublic health relevancepyridinepyrrolineresearch and developmentsmall molecule librariesylide
项目摘要
DESCRIPTION (provided by applicant): N-Heterocycles are essential components of bioactive structures including pharmaceutical entities. Development of novel and efficient synthesis elaborate N-heterocycles will substantially facilitate drug research and development and academic research. Au catalysis has attracted tremendous attention lately due to the exceptional capacities of Au salts/complexes in activating alkynes/allenes/alkenes. Pt catalysts, mostly PtCl2, have shown similar reactivities. Various highly efficient synthetic methods have been developed, especially in the synthesis of carbocycles of various ring sizes and with an array of structural features. However, Au/Pt-catalyzed preparations of N-heterocycles have been rather lagged behind and are mostly limited to simple N-heterocycles (e.g., pyridines, pyrroles, oxazoles, pyrroline and indoles). The goals of this proposal are to develop efficient synthetic methods for elaborate N- heterocycles and to apply them in synthesis of alkaloids and their analogs. Specifically, there are two aims: A. Development of Au/Pt-catalyzed synthesis of N-heterocycles of complexity. Via initial activation of alkynes/allenes with Au/Pt catalysts, more challenging and valuable elaborate N- heterocycles could be formed via two general strategies: a) from relatively simple substrates reactive intermediates can be generated and can undergo further reactions with/without further Au/Pt catalyst participation and lead to enhanced structural complexity; these intermediates include azomethine ylides, nitrones, azomethine imines, all-carbon metal-containing 1,3-dipoles and 1,4-dipoles; b) using relatively complex but readily available substrates, e.g., enynyl lactam/sultam and N-(2-alkynylphenyl)sultam. A range of unimolecular, bimolecular and three-component reactions will be designed and thus allow efficient synthesis of various N-heterocycles, including pyrrolo[2,1-a]isoindoles, indolizines, pyrrolizines, 1,2-heterocycle/carbocycle-fused indoles, pyrrolidinones, tetracyclic indolines, and benzoazepinones/benzoazocinones. Moreover, enantioselective synthesis of these complex N- heterocycles using chiral Au/Pt complexes will also be studied. B. Synthesis of 7-methoxyaziridinomitosene and its analogs A highly efficient, enantioselective synthesis of 7-methoxylaziridinomitosene is proposed via a modular approach. A previously developed Au/Pt-catalyzed efficient formation of 1,2-cyclopentanone-fused indoles will be used as a key transformation for constructing the mitosene skeleton. Using this approach, various aziridinomitosene analogs will be prepared for biological studies.
PUBLIC HEALTH RELEVANCE: This project would develop efficient and versatile synthetic methods to facilitate R&D in drug discovery and lower down manufacturing costs of pharmaceutics. The proposed syntheses of aziridinomitosene analogs will provide new lead structures for cancer treatment.
描述(由申请人提供):N-杂环是生物活性结构(包括药物实体)的基本组分。开发新型、高效的N-杂环精细化合物将极大地促进药物研发和学术研究。由于Au盐/配合物在活化炔/联烯/烯烃方面的优异性能,Au催化近年来引起了人们极大的关注。Pt催化剂,主要是PtCl 2,已经显示出类似的反应性。已经开发了各种高效的合成方法,特别是在各种环尺寸和具有一系列结构特征的碳环的合成中。然而,Au/Pt催化的N-杂环的制备已经相当落后,并且主要限于简单的N-杂环(例如,吡啶、吡咯、恶唑、吡咯啉和吲哚)。本论文的目标是发展高效的N-杂环化合物的合成方法,并将其应用于生物碱及其类似物的合成。具体来说,有两个目标:A。Au/Pt催化合成N-杂环化合物的研究进展通过用Au/Pt催化剂初始活化炔/联烯,可以通过两种一般策略形成更具挑战性和有价值的精细N-杂环:a)从相对简单的底物可以产生反应性中间体,并且可以在有/没有另外的Au/Pt催化剂参与的情况下进行进一步的反应,并导致增强的结构复杂性;这些中间体包括偶氮甲碱叶立德、硝酮、偶氮甲碱亚胺、含全碳金属的1,3-偶极和1,4-偶极; B)使用相对复杂但容易获得的底物,例如,烯炔基内酰胺/磺内酰胺和N-(2-炔基苯基)磺内酰胺。将设计一系列单分子、双分子和三组分反应,从而允许有效合成各种N-杂环,包括吡咯并[2,1-a]异吲哚、中氮茚、吡咯嗪、1,2-杂环/碳环稠合吲哚、吡咯烷酮、四环吲哚啉和苯并氮杂卓酮/苯并氮杂辛酮。此外,还将研究利用手性Au/Pt配合物对映选择性合成这些复杂的N-杂环化合物。B。7-甲氧基氮杂环丙烷及其类似物的合成通过模块化方法提出了7-甲氧基氮杂环丙烷的高效、对映选择性合成。先前开发的Au/Pt催化的1,2-环戊酮稠合吲哚的有效形成将被用作构建线粒体骨架的关键转化。使用这种方法,将制备用于生物学研究的各种氮丙啶类似物。
公共卫生相关性:该项目将开发高效、通用的合成方法,以促进药物发现的研发,降低药物的生产成本。所提出的氮杂环丙烷类似物的合成将为癌症治疗提供新的先导结构。
项目成果
期刊论文数量(29)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Umpolung reactivity of indole through gold catalysis.
- DOI:10.1002/anie.201103014
- 发表时间:2011-08-29
- 期刊:
- 影响因子:16.6
- 作者:Lu, Biao;Luo, Yingdong;Liu, Lianzhu;Ye, Longwu;Wang, Yanzhao;Zhang, Liming
- 通讯作者:Zhang, Liming
Synthesis-enabled probing of mitosene structural space leads to improved IC₅₀ over mitomycin C.
丝裂霉素结构空间的合成探测可提高 IC 值(优于丝裂霉素 C)。
- DOI:10.1002/anie.201402268
- 发表时间:2014
- 期刊:
- 影响因子:0
- 作者:Zheng,Zhitong;Touve,Mollie;Barnes,Josue;Reich,Norbert;Zhang,Liming
- 通讯作者:Zhang,Liming
Alkynes as equivalents of alpha-diazo ketones in generating alpha-oxo metal carbenes: a gold-catalyzed expedient synthesis of dihydrofuran-3-ones.
- DOI:10.1021/ja100041e
- 发表时间:2010-03-17
- 期刊:
- 影响因子:15
- 作者:Ye, Longwu;Cui, Li;Zhang, Guozhu;Zhang, Liming
- 通讯作者:Zhang, Liming
The use of Br/Cl to promote regioselective gold-catalyzed rearrangement of propargylic carboxylates: an efficient synthesis of (1Z, 3E)-1-bromo/chloro-2-carboxy-1,3-dienes.
- DOI:10.1039/c0cc03669b
- 发表时间:2010-12-28
- 期刊:
- 影响因子:0
- 作者:Wang Y;Lu B;Zhang L
- 通讯作者:Zhang L
A flexible and stereoselective synthesis of azetidin-3-ones through gold-catalyzed intermolecular oxidation of alkynes.
通过金催化的炔烃的分子间氧化,将氮杂素-3-酮的柔性和立体选择性合成。
- DOI:10.1002/anie.201007624
- 发表时间:2011-03-28
- 期刊:
- 影响因子:16.6
- 作者:Ye, Longwu;He, Weimin;Zhang, Liming
- 通讯作者:Zhang, Liming
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Liming Zhang其他文献
Liming Zhang的其他文献
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{{ truncateString('Liming Zhang', 18)}}的其他基金
Development of Asymmetric Cooperative Gold Catalysis and Beyond
不对称协同金催化及其他领域的发展
- 批准号:
10546491 - 财政年份:2021
- 资助金额:
$ 25.39万 - 项目类别:
Development of Asymmetric Cooperative Gold Catalysis and Beyond
不对称协同金催化及其他领域的发展
- 批准号:
10322384 - 财政年份:2021
- 资助金额:
$ 25.39万 - 项目类别:
Insertion Into Unactivated/Deactivated C(sp3)-H Bonds Enabled by Oxidatively Generated, Highly Reactive a-Oxo Gold Carbenes: A Safe Non-Diazo yet More Potent Approach
通过氧化生成的高反应性 a-Oxo 金卡宾插入未活化/失活的 C(sp3)-H 键:一种安全的非重氮且更有效的方法
- 批准号:
9449301 - 财政年份:2017
- 资助金额:
$ 25.39万 - 项目类别:
Development of novel approaches for stereoselective construction of glycosidic linkages
糖苷键立体选择性构建新方法的开发
- 批准号:
9391624 - 财政年份:2017
- 资助金额:
$ 25.39万 - 项目类别:
Insertion Into Unactivated/Deactivated C(sp3)-H Bonds Enabled by Oxidatively Generated, Highly Reactive a-Oxo Gold Carbenes: A Safe Non-Diazo yet More Potent Approach
通过氧化生成的高反应性 a-Oxo 金卡宾插入未活化/失活的 C(sp3)-H 键:一种安全的非重氮且更有效的方法
- 批准号:
10001071 - 财政年份:2017
- 资助金额:
$ 25.39万 - 项目类别:
Insertion Into Unactivated/Deactivated C(sp3)-H Bonds Enabled by Oxidatively Generated, Highly Reactive a-Oxo Gold Carbenes: A Safe Non-Diazo yet More Potent Approach
通过氧化生成的高反应性 a-Oxo 金卡宾插入未活化/失活的 C(sp3)-H 键:一种安全的非重氮且更有效的方法
- 批准号:
9751339 - 财政年份:2017
- 资助金额:
$ 25.39万 - 项目类别:
Au/Pt Catalysis in the Synthesis of Elaborate N-Heterocycles: Methodology Develop
Au/Pt 催化合成精细 N-杂环化合物:方法开发
- 批准号:
8126457 - 财政年份:2009
- 资助金额:
$ 25.39万 - 项目类别:
Au/Pt Catalysis in the Synthesis of Elaborate N-Heterocycles: Methodology Develop
Au/Pt 催化合成精细 N-杂环化合物:方法开发
- 批准号:
7939682 - 财政年份:2009
- 资助金额:
$ 25.39万 - 项目类别:
Au/Pt Catalysis in the Synthesis of Elaborate N-Heterocycles: Methodology Develop
Au/Pt 催化合成精细 N-杂环化合物:方法开发
- 批准号:
8324555 - 财政年份:2009
- 资助金额:
$ 25.39万 - 项目类别:
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