Regio- and Site-Selective Processes Using Transition Metal and Biological Catalysts
使用过渡金属和生物催化剂的区域和位点选择性过程
基本信息
- 批准号:9250166
- 负责人:
- 金额:$ 40.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-01 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAlkenesAlkynesBiologicalBiological ProcessBiological Response Modifier TherapyBiologyBiomedical ResearchCarbohydrate ChemistryCarbohydratesCatalysisChemical StructureChemistryComplexCytochrome P450DevelopmentEngineeringEnzymesGenerationsGlycosidesGoalsHydrogen BondingMediatingMethodologyMethodsMolecularPlayPreparationProcessPropertyReagentResearchRoleSilanesSiteSpeedStructureTherapeuticTransition ElementsWorkbiological preparationcatalystcostimprovedinsightinterdisciplinary approachmethod developmentmultidisciplinarynovelnovel strategiesoxidationprogramspublic health relevancesmall moleculestereochemistry
项目摘要
DESCRIPTION (provided by applicant): Rapid and reliable access to synthetically-derived chemical structures plays an essential role in many aspects of biomedical research. The underlying objective of this proposal is to provide fundamentally new strategies for highly selective bond formations that will enable more rapid and efficient access to biologically active compounds of potential therapeutic value. A common theme throughout the proposal is the development of methods that accomplish highly selective bond formations when two or more similarly reactive parts of a structure are present. Using small molecule transition metal catalysts, the regioselective derivatization of simple structural subunits such as alkenes and alkynes will be addressed. Through careful mechanistic analysis, new insights will be provided to guide general strategies toward this objective in a broad range of contexts. Using engineered biological catalysts, strategies will be developed to enable regioselective oxidations of C-H bonds in complex substrates, using a novel substrate engineering approach that directs cytochrome P450-mediated oxidations towards a desired C-H bond embedded within a complex molecular framework. The development of new methods for the installation of carbohydrates will also be addressed. A new class of carbohydrate-derived silane reagents will enable considerable generality and control of stereochemistry during the installation of glycosidic bonds. The goals of this research program, including the precise generation of molecular frameworks, the selective oxidation of C-H bonds, and the installation of stereodefined carbohydrates, are all highly effective strategies for impacting and enhancing the biological properties of complex structures. Put together, the strategies present a toolbox of methods for enabling novel approaches for the synthesis of bioactive compounds. In collaborative work, these studies will be combined with the unique capabilities of biosynthetic enzymes to provide a synergistic combination of synthesis and biocatalysis to address key hurdles in the preparation of biologically active structures. The approach represents a merger of rarely combined fields of chemistry and biology: transition metal catalysis, C-H oxidation methodology, carbohydrate chemistry, and biocatalysis. This unique multidisciplinary perspective allows examination of strategies that cannot be addressed by conventional approaches. The improved entries to biomedically important structures made possible by this research will enable their biological function and therapeutic potential to be more efficiently studied.
描述(由申请人提供):快速可靠地获得合成衍生的化学结构在生物医学研究的许多方面起着至关重要的作用。该提案的根本目标是提供用于高度选择性键形成的全新策略,其将使得能够更快速和有效地获得具有潜在治疗价值的生物活性化合物。整个提案的一个共同主题是开发当结构中存在两个或更多类似反应部分时实现高度选择性键形成的方法。使用小分子过渡金属催化剂,区域选择性衍生化的简单结构的亚基,如烯烃和炔烃将被解决。通过仔细的机制分析,将提供新的见解,以指导在广泛的背景下实现这一目标的一般战略。使用工程化的生物催化剂,将开发策略,使区域选择性氧化的复杂底物中的C-H键,使用一种新的底物工程方法,直接细胞色素P450介导的氧化对所需的C-H键嵌入在一个复杂的分子框架。还将讨论碳水化合物安装新方法的开发。一类新的碳水化合物衍生的硅烷试剂将使相当大的通用性和控制的立体化学过程中的糖苷键的安装。该研究计划的目标,包括分子框架的精确生成,C-H键的选择性氧化以及立体定向碳水化合物的安装,都是影响和增强复杂结构生物学特性的高效策略。总之,这些策略提供了一个方法工具箱,用于实现生物活性化合物合成的新方法。在合作工作中,这些研究将与生物合成酶的独特能力相结合,以提供合成和生物催化的协同组合,以解决制备生物活性结构的关键障碍。该方法代表了化学和生物学领域很少结合的合并:过渡金属催化,C-H氧化方法,碳水化合物化学和生物催化。这一独特的多学科视角允许审查传统方法无法解决的战略。这项研究使生物医学重要结构的改进条目成为可能,将使它们的生物功能和治疗潜力得到更有效的研究。
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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JOHN MONTGOMERY其他文献
JOHN MONTGOMERY的其他文献
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{{ truncateString('JOHN MONTGOMERY', 18)}}的其他基金
Michigan Chemistry-Biology Interface Training Program
密歇根化学-生物界面培训计划
- 批准号:
10187591 - 财政年份:2019
- 资助金额:
$ 40.69万 - 项目类别:
Catalytic Methods for Building Block Assembly and for Stereoselective Glycosylation
构建块组装和立体选择性糖基化的催化方法
- 批准号:
9391258 - 财政年份:2017
- 资助金额:
$ 40.69万 - 项目类别:
Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis
使用主族和过渡金属催化的区域和位点选择性过程
- 批准号:
10610494 - 财政年份:2016
- 资助金额:
$ 40.69万 - 项目类别:
Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis
使用主族和过渡金属催化的区域和位点选择性过程
- 批准号:
10202252 - 财政年份:2016
- 资助金额:
$ 40.69万 - 项目类别:
Supplement: Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis
补充:使用主族和过渡金属催化的区域和位点选择性过程
- 批准号:
10388498 - 财政年份:2016
- 资助金额:
$ 40.69万 - 项目类别:
Regio- and Site-Selective Processes Using Transition Metal and Biological Catalysts
使用过渡金属和生物催化剂的区域和位点选择性过程
- 批准号:
9891068 - 财政年份:2016
- 资助金额:
$ 40.69万 - 项目类别:
Regio- and Site-Selective Processes Using Main Group and Transition Metal Catalysis
使用主族和过渡金属催化的区域和位点选择性过程
- 批准号:
10378698 - 财政年份:2016
- 资助金额:
$ 40.69万 - 项目类别:
Regio- and Site-Selective Processes Using Transition Metal and Biological Catalysts
使用过渡金属和生物催化剂的区域和位点选择性过程
- 批准号:
9071536 - 财政年份:2016
- 资助金额:
$ 40.69万 - 项目类别:
Supplement: Regio- and Site-Selective Processes Using Transition Metal and Biological Catalysts
补充:使用过渡金属和生物催化剂的区域和位点选择性过程
- 批准号:
9708114 - 财政年份:2016
- 资助金额:
$ 40.69万 - 项目类别:
New Cyclization Methods and Multicomponent Couplings
新的环化方法和多组分偶联
- 批准号:
7907102 - 财政年份:2009
- 资助金额:
$ 40.69万 - 项目类别:
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