Stereoselective Synthesis via Metallacycle-Mediated Bond Construction
通过金属环介导的键构建进行立体选择性合成
基本信息
- 批准号:8372060
- 负责人:
- 金额:$ 40.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-03-12 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAlcoholsAlkaloidsAlkenesAlkynesAminesAntifungal AntibioticsBiologicalBiological FactorsBiologyChemicalsChemistryComplexCouplingDataDependenceDevelopmentFatty AcidsFoundationsFundingFutureIminesLaboratoriesMediatingMedicineMethodologyMethodsNicotinic ReceptorsOrganic ChemistryOrganic SynthesisOxidation-ReductionPathway interactionsPharmaceutical ChemistryPhasePlayPositioning AttributeProcessProgram DevelopmentPropertyRanaReactionReportingResearchRoleRouteSchemeScientific Advances and AccomplishmentsTechnologybasecarbonyl groupchemical reactionchemical synthesiscombinatorial chemistrycycloadditiondesigndienekendomycinmethod developmentnitronenovelnovel strategiesprogramssmall molecule
项目摘要
:
Chemical processes that enable fragment union between complex coupling partners define a subset of
reactions that are exceptionally powerful. While they can help to define efficient pathways to complex
molecules, they are also of central importance to combinatorial and medicinal chemistry. Despite the
importance of such coupling reactions in chemical synthesis, it is surprising that only a handful of robust
pathways are available for bimolecular C-C bond formation between highly functionalized coupling partners.
The research program outlined in this proposal is focused on establishing a new approach to stereoselective
chemical synthesis that derives from discovery and application of novel metallacycle-mediated bimolecular C-
C bond forming reactions in natural product synthesis.
Our first phase of funding for GM080266 was focused on methods development, and a great many
reactions have been discovered/reported over the last five years. We are now in a position to develop these
unique modes of reactivity in the context of target-oriented synthesis. This is a critical component of the
scientific advance we aim to make, as reaction methods need to be vetted in complex settings to explore their
true potential in impacting medicinally relevant pursuits. As such, we will pursue the application of our
technology to the syntheses of a range of structurally diverse and rare natural products (alkaloids, fatty acids
and polyketides) that are known to possess significant and medicinally relevant biological activities.
Overall, the program proposed will result in: (1) confirming the utility of metallacycle-mediated cross-
coupling technology in complex molecule synthesis, (2) the elucidation of a range of novel retrosynthetic
strategies in target-oriented synthesis, and (3) the first, or the most concise, syntheses of a range of natural
products including, the alkaloid 205B, ripostatin A, borrelidin and kendomycin. Therefore, our proposed
studies will aim to advance the emerging modes of chemical reactivity supported by GM080266 from a
foundation of reaction methodology to a powerful class of stereoselective fragment coupling reactions of
profound utility in target-oriented synthesis. As such, successful development of this program will offer
advances in stereoselective synthesis that have great potential to impact the search for medicinally relevant
small molecules via enabling future scientific discovery at the interface of chemistry with biology and medicine.
II.
:
使复杂偶联伙伴之间的片段结合成为可能的化学过程定义了
反应异常强烈。虽然它们可以帮助定义通往复杂环境的有效途径
除了分子,它们对组合化学和药物化学也是至关重要的。尽管
这种偶联反应在化学合成中的重要性,令人惊讶的是,只有少数人健壮
在高度官能化的偶联伙伴之间形成双分子C-C键的途径是可用的。
这项提案中概述的研究计划的重点是建立一种新的立体选择方法
新型金属环介导型双分子碳链化合物的发现与应用
天然产物合成中的C键形成反应。
我们为GM080266提供的第一阶段资金主要集中在方法开发上,以及许多
在过去的五年里,人们已经发现/报道了这些反应。我们现在有能力开发这些
在以目标为导向的合成背景下的独特的反应模式。这是
我们的目标是取得科学进展,因为反应方法需要在复杂的环境中进行审查,以探索其
在影响医学相关追求方面的真正潜力。因此,我们将继续应用我们的
合成一系列结构多样的稀有天然产物(生物碱、脂肪酸)的技术
和聚酮),已知具有显著的和医学上相关的生物活性。
总体而言,提出的方案将导致:(1)确认金属环介导的交叉反应的效用。
复杂分子合成中的偶联技术,(2)一系列新型逆合成化合物的阐明
目标导向合成中的策略,以及(3)一系列天然化合物的第一次或最简明的合成
产品包括生物碱205B、瑞波他丁A、冬凌草素和肯德霉素。因此,我们建议
研究的目的将是推动GM080266支持的新的化学反应模式从
一类功能强大的立体选择性片段偶联反应方法学的建立
在面向目标的合成中具有深远的实用价值。因此,该计划的成功开发将提供
立体选择性合成对药物相关研究有很大影响的研究进展
通过在化学、生物和医学的界面上实现未来的科学发现,实现小分子。
二、
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
GLENN C MICALIZIO其他文献
GLENN C MICALIZIO的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('GLENN C MICALIZIO', 18)}}的其他基金
Metallacycle-mediated coupling in stereoselective synthesis
立体选择性合成中金属环介导的偶联
- 批准号:
10540398 - 财政年份:2020
- 资助金额:
$ 40.59万 - 项目类别:
Metallacycle-mediated coupling in stereoselective synthesis
立体选择性合成中金属环介导的偶联
- 批准号:
10317087 - 财政年份:2020
- 资助金额:
$ 40.59万 - 项目类别:
Class II Directed Carbometalation Processes for Heterocycle Synthesis
用于杂环合成的 II 类定向碳金属化工艺
- 批准号:
7891992 - 财政年份:2009
- 资助金额:
$ 40.59万 - 项目类别:
Class II Directed Carbometalation Processes for Heterocycle Synthesis
用于杂环合成的 II 类定向碳金属化工艺
- 批准号:
8037034 - 财政年份:2007
- 资助金额:
$ 40.59万 - 项目类别:
Stereoselective Synthesis via Metallacycle-Mediated Bond Construction
通过金属环介导的键构建进行立体选择性合成
- 批准号:
8535780 - 财政年份:2007
- 资助金额:
$ 40.59万 - 项目类别:
Stereoselective Synthesis via Metallacycle-Mediated Bond Construction
通过金属环介导的键构建进行立体选择性合成
- 批准号:
8664650 - 财政年份:2007
- 资助金额:
$ 40.59万 - 项目类别:
Class II Directed Carbometalation Processes for Heterocycle Synthesis
用于杂环合成的 II 类定向碳金属化工艺
- 批准号:
7382520 - 财政年份:2007
- 资助金额:
$ 40.59万 - 项目类别:
Class II Directed Carbometalation Processes for Heterocycle Synthesis
用于杂环合成的 II 类定向碳金属化工艺
- 批准号:
7572838 - 财政年份:2007
- 资助金额:
$ 40.59万 - 项目类别:
Stereoselective Synthesis via Metallacycle-Mediated Bond Construction
通过金属环介导的键构建进行立体选择性合成
- 批准号:
8652468 - 财政年份:2007
- 资助金额:
$ 40.59万 - 项目类别:
Class II Directed Carbometalation Processes for Heterocycle Synthesis
用于杂环合成的 II 类定向碳金属化工艺
- 批准号:
7771722 - 财政年份:2007
- 资助金额:
$ 40.59万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 40.59万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 40.59万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 40.59万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 40.59万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 40.59万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 40.59万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 40.59万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 40.59万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 40.59万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 40.59万 - 项目类别:
Grant-in-Aid for Early-Career Scientists