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Complexity-building Approaches in Photoassisted Synthesis of Heterocycles

光辅助合成杂环的复杂性构建方法

基本信息

批准号：
1955892
负责人：
Andrei Kutateladze
金额：
$ 48万
依托单位：
University of Denver
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955892&HistoricalAwards=false
关键词：
Complexity building Approaches Photoassisted Synthesis

项目摘要

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Andrei Kutateladze, Department of Chemistry and Biochemistry at the University of Denver. The research is focused on developing new methods for synthesis of complex organic molecules containing multiple ring substructures. This will be done using photons of light as an environmentally abundant and safe reagent and the approach achieves structural complexity with a minimal number of experimental steps. Besides the fundamental importance of learning about interactions of light and matter in the context of synthetic chemistry, the targeted complex polyheterocycles (i.e. molecules which contain nitrogen, sulfur, or oxygen atoms as a part of a ring) are intentionally designed to resemble alkaloids (a class of naturally occurring organic bases) and other biologically active natural products that may potentially possess useful therapeutic properties. Importantly, this award supports research experiences for undergraduate and graduate students, especially those from historically underrepresented groups in science, provided them with useful skill sets in modern organic chemistry and photochemistry; excellent preparation for career paths in either academia or industry.This research expands the toolbox for excited state intramolecular proton transfer (ESIPT)-based synthetic photochemistry with several new photo-assisted synthetic reaction cascades. The photo-induced reaction cascades allow the experimentalist to achieve large step-normalized complexity increases and rapidly assemble novel fused polyheterocyclic molecular architectures. Additional growth of complexity is realized through post-photochemical transformations, such as multi-step carbocationic cascades and rearrangements. Investigations of reaction mechanisms and stereochemistry of these ESIPT-triggered cascades help achieve control of stereochemical and regiochemical outcomes. This experimental work is augmented by computation, especially to facilitate solution structure elucidation of the complex polyheterocyclic products by NMR. The new integrated DU8+ method for fast and accurate calculation of NMR parameters includes PCM models and solvent-specific parameterization schemes. This computational tool is are critical for success of this project, but also has broader implications for structure elucidation of complex synthetic and natural product target molecules. Additionally, this research provides hands-on laboratory training for graduate and undergraduate students, and research associates, especially those from historically underrepresented groups in science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，NSF化学部的化学合成计划正在支持丹佛大学化学和生物化学系Andrei Kutateladze教授的研究。该研究的重点是开发新的方法来合成含有多环亚结构的复杂有机分子。这将使用光子作为环境丰富和安全的试剂来完成，并且该方法以最少的实验步骤实现结构复杂性。除了在合成化学的背景下了解光和物质的相互作用的基本重要性之外，目标复杂的多杂环（即含有氮，硫或氧原子作为环的一部分的分子）被故意设计成类似生物碱（一类天然存在的有机碱）和其他可能具有有用的治疗特性的生物活性天然产物。重要的是，该奖项支持本科生和研究生的研究经验，特别是那些历史上在科学中代表性不足的群体，为他们提供了现代有机化学和光化学的有用技能;这项研究扩展了激发态分子内质子转移（ESIPT）为基础的合成光化学的工具箱，其中包括几种新的光化学方法，辅助合成反应级联。光诱导反应级联允许实验者实现大的步骤归一化的复杂性增加，并快速组装新的稠合多杂环分子结构。复杂性的额外增长是通过后光化学转化实现的，例如多步碳阳离子级联和重排。这些ESIPT引发的级联反应的反应机理和立体化学的调查有助于实现控制的立体化学和区域化学的结果。该实验工作通过计算得到增强，特别是通过NMR促进复杂多杂环产物的溶液结构解析。用于快速准确计算NMR参数的新集成DU 8+方法包括PCM模型和溶剂特定参数化方案。这种计算工具对于该项目的成功至关重要，但对于复杂合成和天然产物靶分子的结构解析也具有更广泛的意义。此外，这项研究还为研究生和本科生以及研究助理提供了动手实验室培训，特别是那些来自历史上代表性不足的科学团体的人。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。