Excited state intramolecular proton transfer-based photoassisted methodologies to access complex molecular architectures

基于激发态分子内质子转移的光辅助方法来获取复杂的分子结构

基本信息

批准号：
1665342
负责人：
Andrei Kutateladze
金额：
$ 37.14万
依托单位：
University of Denver
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1665342&HistoricalAwards=false
关键词：
Excited state intramolecular proton transfer

项目摘要

In this project funded by the Chemical Synthesis Program, Professor Andrei Kutateladze of the Department of Chemistry and Biochemistry at University of Denver develops new methods for the synthesis of complex organic heterocycles. These are substances which contain nitrogen in a ring, a common feature of natural products and pharmaceuticals. New synthetic routes are primarily based on novel cycloaddition reactions initiated by ultraviolet light. Complex multi-ring heterocyclic molecular architectures are accessed and alkaloid mimics are synthesized. Fundamental new science includes the development of cascade photoreactions to form multiple chemical bonds in one experimentally simple step. In addition, this award supports research experiences for undergraduate and graduate students, especially those from historically underrepresented groups in science.This research expands the excited state intramolecular proton transfer (ESIPT) based synthetic photochemistry tool box with new photoassisted cascade methodology. New reactions provide access to complex polyheterocyclic compounds in a controlled atom- and step-economical fashion. The mechanism of these cascade processes, including quantum mechanical tunneling at the hydrogen transfer step, is elucidated to better modulate stereochemical and regiochemical outcomes. Such control is needed to develop the capability of systematically screening the chemical space in search of novel polyheterocyclic molecular architectures with the requisite scaffold diversity. To further grow scaffold complexity and diversity and to decorate the core scaffolds with additional functional groups and heterocyclic pendants, experimentally simple postphotochemical steps are deployed after the light-induced transformation. This experimental work is accompanied by the development of computational methods for fast and accurate predictions of NMR spectra, which is critical for success of this project, but also has broader implications for structure elucidation of complex synthetic and natural organic molecules. Additionally, this research provides hands-on laboratory training for graduate and undergraduate students, especially those from historically underrepresented groups in science.

在该项目由化学合成计划资助的项目中，丹佛大学化学和生物化学系的Andrei Kutateladze教授开发了合成复杂有机杂环的新方法。这些物质在环上包含氮，这是天然产物和药物的共同特征。新的合成途径主要基于紫外线引发的新型环加成反应。访问复杂的多环杂环分子结构，并合成生物碱模拟物。基本的新科学包括开发级联光反应，以在一个实验性的简单步骤中形成多种化学键。此外，该奖项还支持针对本科生和研究生的研究经验，尤其是从历史上代表性不足的科学群体中的研究经验。这项研究扩大了激发的状态分子内质子转移（ESIPT）基于合成的综合光化学工具盒，并具有新的光明级别辅助方法。新反应以受控的原子和阶跃经济方式提供了对复杂的多粒细胞化合物的访问。这些级联过程的机理，包括在氢转移步骤处进行量子机械隧穿的机理，以更好地调节立体化学和条款化学结果。需要这样的控制来发展系统地筛选化学空间的能力，以寻找具有必要的支架多样性的新型多粒分子体系结构。为了进一步增强脚手架的复杂性和多样性，并通过其他功能组和异环式吊坠来装饰核心支架，在光诱导的转化后，部署了实验简单的经科后步骤。这项实验性工作伴随着开发用于快速准确预测NMR光谱的计算方法，这对于该项目的成功至关重要，但对复杂合成和天然有机分子的结构阐明具有更大的影响。此外，这项研究为研究生和本科生提供了实验室培训，尤其是从历史上代表性不足的科学群体中的研究生培训。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Structure Validation of Complex Natural Products: Time to Change the Paradigm. What did Synthesis of Alstofolinine A Prove?

DOI：
10.1021/acs.joc.9b00969
发表时间：
2019-06-21
期刊：
JOURNAL OF ORGANIC CHEMISTRY
影响因子：
3.6
作者：
Kutateladze, Andrei G.;Holt, Tina
通讯作者：
Holt, Tina

The Discreet Structural Diversity of Briarellins: DU8+ Guided Multiple Structure Revisions Yielded Two Unknown Structural Types

Briarellins 的谨慎结构多样性：DU8 引导的多重结构修改产生了两种未知的结构类型

DOI：
10.1021/acs.joc.0c00555
发表时间：
2020
期刊：
The Journal of Organic Chemistry
影响因子：
0
作者：
Holt, Tina A.;Reddy, D. Sai;Huple, Deepak B.;West, Lyndon M.;Rodríguez, Abimael D.;Crimmins, Michael T.;Kutateladze, Andrei G.
通讯作者：
Kutateladze, Andrei G.

Step-Economical Photoassisted Diversity-Oriented Synthesis: Sustaining Cascade Photoreactions in Oxalyl Anilides to Access Complex Polyheterocyclic Molecular Architectures

DOI：
10.1021/jacs.7b07598
发表时间：
2017-11-22
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Kuznetsov, Dmitry M.;Kutateladze, Andrei G.
通讯作者：
Kutateladze, Andrei G.

Diastereoselective heterocyclization of geminal bromo-fluoro arylcyclopropanes by nitrosonium tetrafluoroborate: Access to 4-fluorinated isoxazolines and isoxazoles

四氟硼酸亚硝基对偕溴氟芳基环丙烷的非对映选择性杂环化：获得 4-氟化异恶唑啉和异恶唑

DOI：
10.1016/j.tet.2019.130666
发表时间：
2019
期刊：
Tetrahedron
影响因子：
2.1
作者：
Bondarenko, Oksana B.;Komarov, Arseniy I.;Karetnikov, George L.;Nikolaeva, Svetlana N.;Zyk, Nikolai V.;Holt, Tina;Kutateladze, Andrei G.
通讯作者：
Kutateladze, Andrei G.

Natural Products Containing the Oxetane and Related Moieties Present Additional Challenges for Structure Elucidation: A DU8+ Computational Case Study