RII Track-4: in situ SSNMR Spectroscopy of Base Catalysts Used to Produce Statin Drugs

药物和药物构件的生产通常是使用传统的化学合成方法完成的。不幸的是，这些方法会产生大量的废物，并且起始材料通常是不可再生的。然而，生物质的可得性及其组成部分（如糖）的最新发展为生产高价值化学品（如药物前体）提供了可持续的原料。之前的工作已经开发了将糖转化为3-羟基- γ -丁内酯（HBL）的催化方法，HBL是他汀类药物（如Crestor®和Lipitor®）的重要组成部分。这个项目的重点是加强缅因大学和艾姆斯实验室之间的合作，这将有助于阐明这些催化剂上发生的化学反应。特别是，我们将使用固态核磁共振波谱（SSNMR）来识别吸附在催化剂表面的化学物质的结构，并跟踪反应过程。这种对这些催化剂运作的分子水平的理解对于设计新的、改进的材料是至关重要的，这些材料可以进一步提高利用可再生资源合成药物的效率。该项目旨在对固体CaCO3催化剂表面发生的化学反应有一个基本的了解，该催化剂被认为是通过反醛醇反应产生羟基- γ -丁内酯（HBL）。与Ames实验室的核磁共振波谱（NMR）小组合作，原位13C固态核磁共振（SSNMR）将用于跟踪HBL生产的时间过程，这将允许识别反应中重要的表面中间体，并阐明由ca基催化剂进行的反应机理。随后，将利用动态核极化13C SSNMR的高灵敏度进行同核相关谱分析，以确定吸附在CaCO3表面的分子构型。这些基本的机理见解将是发展固体碱催化剂的关键，不仅适用于HBL的生产，也适用于其他与生物质相关的反应。此外，PI和Ames实验室核磁共振小组之间的合作将允许在国内机构开发额外的SSNMR专业知识，并将提供进一步访问先进的SSNMR资源。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The production of pharmaceuticals and pharmaceutical building blocks often is accomplished using traditional chemical synthesis methods. Unfortunately, these methods can produce substantial waste products, and the starting materials are often non-renewable. Recent developments in the availability of biomass and its building blocks (e.g., sugars), however, provides a sustainable feedstock for producing high-value chemicals, such as pharmaceutical precursors. Previous work has developed catalytic methods for converting sugars into 3-hydroxy-gamma-butyrolactone (HBL), which is an important building block for statin drugs such as Crestor® and Lipitor®. This project is focused on strengthening collaborative efforts between the University of Maine and the Ames Laboratory, which will facilitate elucidation of the chemistry that occurs on these catalysts. In particular, we will use solid-state nuclear magnetic resonance spectroscopy (SSNMR) to identify the structures of chemical species adsorbed on the surface of the catalyst and to track the reaction progress. Such a molecular-level understanding of the operation of these catalysts is critical for the design of new, improved materials that can further improve the efficiency of pharmaceutical synthesis using renewable resources.This project seeks to develop a fundamental understanding of the chemistry that occurs at the surface of a solid CaCO3 catalyst used to produce hydroxy-gamma-butyrolactone (HBL) via what is believed to be a retro-Aldol reaction. In collaboration with the nuclear magnetic resonance spectroscopy (NMR) groups at the Ames Laboratory, in situ 13C solid-state NMR (SSNMR) will be used to follow the time-course of HBL production, which will allow for the identification of important surface intermediates in the reaction, and elucidation of the reaction mechanism as carried out by Ca-based catalysts. Subsequently, the high sensitivity afforded by dynamic nuclear polarization 13C SSNMR will be used to perform homonuclear correlation spectroscopy to identify the configurations of molecules adsorbed on the CaCO3 surface. These fundamental mechanistic insights will be key for the development of solid base catalysts for not only HBL production but also other biomass-related reactions. Moreover, the collaboration between the PI and the NMR groups at the Ames Laboratory will allow for the development of additional SSNMR expertise at the home institution and will provide further access to advanced SSNMR resources.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.