Innovation in Catalyst and Oxidative Amination Reaction Development for the Synthesis of Darobactin and Other Ribosomally Synthesized Post-translationally Modified Peptides (RiPPs)
用于合成 Darobactin 和其他核糖体合成的翻译后修饰肽 (RiPP) 的催化剂和氧化胺化反应开发的创新
基本信息
- 批准号:10259785
- 负责人:
- 金额:$ 30.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-20 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcetatesAddressAlkenesAmidesAminationAmino AcidsAntibioticsBindingBioinformaticsBiologicalCatalysisChemicalsChemistryCodeCollaborationsComplexCouplingDevelopmentDrug TargetingEnzymesExhibitsFamilyGene ClusterGenerationsHydrogen BondingInvestigationMembrane ProteinsMetalsNatural ProductsPalladiumParentsPeptidesPharmacologic SubstanceReactionResearchRhodiumRibosomesStructureSystemTransition Elementsamidationcatalystcrosslinkdesigndrug discoveryfrontierinnovationnovelpathogenpeptide structurequorum sensingtool
项目摘要
Project Summary
In this proposal we have outlined a plan to develop a new family of planar chiral indenyl Co, Rh,
and Ir catalysts that will be broadly applicable in the development of new oxidative amination
reactions. This represents a significant innovation in catalysis. Catalyst development is presented
in the context of allylic C-H functionalizations, which represent a contemporary frontier of group
IX metal catalysis, in which C-H functionalization relies on the innate reactivity of the C-H bond,
and does not require a Lewis basic directing group. Our preliminary results support the hypothesis
that the rhodium catalysts described in this proposal will enable a significantly expanded pool of
viable nucleophiles and alkene substrates when compared to prior state-of-the-art palladium
catalyzed allylic C-H functionalization. Mechanistic studies demonstrate that the parent RhCp*
platform provides products via a common allylic acetate intermediate, obtained via oxidatively
induced reductive elimination. These mechanistic investigations provide hypothesis driven 2nd
generation catalyst and reaction designs to control regio- and enantioselectivity. Preliminary
results demonstrate that the new catalyst platform is broadly applicable for enantioselective
catalysis beyond allylic C-H functionalization reactions. The full development of these reactions
represents a particularly significant advance in the synthesis of non-canonical amino acids,
peptides, and amide containing natural products and pharmaceuticals. The new reactions and
catalysts are developed for the synthesis of emerging ribosomally synthesized posttranslationally
modified peptide (RiPP) natural products, discovered through bioinformatic analysis, and
presenting novel structural motifs. In the long term, the realization of the chemistry described in
this proposal will provide powerful new tools for drug discovery chemists to invent new
pharmaceuticals.
项目摘要
在这个建议中,我们概述了一个计划,以开发一个新的家庭的平面手性茚基Co,Rh,
和Ir催化剂,将广泛应用于新的氧化胺化的开发
反应.这是催化领域的一项重大创新。介绍了催化剂的发展
在烯丙基C-H官能化的背景下,这代表了当代组的前沿,
IX金属催化,其中C-H官能化依赖于C-H键的固有反应性,
并且不需要刘易斯碱性导向基团。我们的初步结果支持这一假设
在该提议中描述的铑催化剂将使得能够显著地扩大
当与现有技术的钯相比时,
催化的烯丙基C-H官能化。机制研究表明,母体RhCp*
平台通过氧化获得的常见乙酸烯丙酯中间体提供产品
诱导还原消除。这些机制研究提供了假设驱动的第二个
生成催化剂和反应设计以控制区域和对映选择性。初步
结果表明,该催化剂平台具有广泛的应用前景,
催化烯丙基C-H官能化反应。这些反应的充分发展
代表了非规范氨基酸合成的一个特别重要的进展,
肽和含酰胺的天然产物和药物。新的反应和
开发了用于合成新兴的核糖体后合成的催化剂
通过生物信息学分析发现的修饰肽(RiPP)天然产物,以及
呈现出新颖的结构图案。从长远来看,
这一提议将为药物发现化学家提供强有力的新工具,
大药厂
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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Simon B. Blakey其他文献
Synthetic Routes for Heteroatom‐Containing Alkylated/Arylated Polycyclic Aromatic Hydrocarbons
含杂原子烷基化/芳基化多环芳烃的合成路线
- DOI:
10.1002/ange.202014108 - 发表时间:
2020-12 - 期刊:
- 影响因子:0
- 作者:
Qinqin Shi;Xiaosong Shi;Changfu Feng;Yishi Wu;Nan Zheng;Jie Liu;Xiaoxi Wu;Hao Chen;Aidong Peng;Jianfeng Li;Lang Jiang;Hongbing Fu;Zengqi Xie;Seth R. Marder;Simon B. Blakey;Hui Huang - 通讯作者:
Hui Huang
Simon B. Blakey的其他文献
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{{ truncateString('Simon B. Blakey', 18)}}的其他基金
Innovation in Catalyst and Oxidative Amination Reaction Development for the Synthesis of Darobactin and Other Ribosomally Synthesized Post-translationally Modified Peptides (RiPPs)
用于合成 Darobactin 和其他核糖体合成的翻译后修饰肽 (RiPP) 的催化剂和氧化胺化反应开发的创新
- 批准号:
10469565 - 财政年份:2020
- 资助金额:
$ 30.5万 - 项目类别:
Innovation in Catalyst and Oxidative Amination Reaction Development for the Synthesis of Darobactin and Other Ribosomally Synthesized Post-translationally Modified Peptides (RiPPs)
用于合成 Darobactin 和其他核糖体合成的翻译后修饰肽 (RiPP) 的催化剂和氧化胺化反应开发的创新
- 批准号:
10688236 - 财政年份:2020
- 资助金额:
$ 30.5万 - 项目类别:
Novel Radical Reactions for C-C Bond Formation
C-C 键形成的新颖自由基反应
- 批准号:
10371873 - 财政年份:2018
- 资助金额:
$ 30.5万 - 项目类别:
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