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

在这个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。这些物质在环中含有氮，这是天然产品和药品的共同特征。新的合成路线主要基于紫外光引发的新型环加成反应。获得了复杂的多环杂环分子结构，并合成了生物碱模拟物。基础性的新科学包括发展级联光反应，在一个简单的实验步骤中形成多个化学键。此外，该奖项还支持本科生和研究生的研究经验，特别是那些来自科学领域历史上代表性不足的群体的研究经验。这项研究利用新的光助级联方法扩展了基于激发态分子内质子转移(ESIPT)的合成光化学工具箱。新的反应提供了以受控的原子和步骤经济的方式获得复杂的多杂环化合物的途径。阐明了这些级联过程的机制，包括氢转移步骤中的量子力学隧道效应，以更好地调节立体化学和区域化学结果。这种控制是发展系统地筛选化学空间以寻找具有必要支架多样性的新的多杂环分子结构的能力所必需的。为了进一步提高支架的复杂性和多样性，并用额外的官能团和杂环悬挂物装饰核心支架，在光诱导转化后进行了实验上简单的光后化学步骤。伴随着这项实验工作的是快速准确预测核磁共振谱的计算方法的发展，这对这个项目的成功至关重要，但对复杂的合成和天然有机分子的结构解释也有更广泛的影响。此外，这项研究还为研究生和本科生提供了动手实验室培训，特别是那些来自科学界历史上代表性不足的群体的学生。

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.