Boron Chemistry for Catalysis and Drug Discovery

本研究项目结合了基础科学和应用科学，以绿色化学和药物发现的两个相关目标为目标：亲核官能团（如醇、胺、羧酸）的催化活化，以及药物发现中化合物类别的缺乏。为了实现这些目标，霍尔博士将研究半硼杂环，一类稳定的含硼有机化合物，因为它们具有与醇和其他亲核（富电子）官能团交换硼氧键的潜在能力，并利用这些独特的化合物作为有用化学反应的催化剂和药物发现的支架。为了实现这些应用，首先必须确定或设计新的含硼杂环，这些杂环具有在所需条件下与亲核基团相互作用的能力。亲核试剂是富含电子的官能团（如醇、胺），它们可以通过“缩合”反应释放出水分子，取代亲电（缺电子）原子（如硼）上的其他基团。因此，通过使用先进的质谱（MS）和核磁共振技术，将设计出快速、准确和通用的方法来探测常见官能团和氨基酸侧链与半硼酸相互作用的能力。利用这些知识，将设计新的催化剂，使具有挑战性的合成转化感兴趣的药物化学，如醇的直接功能化。醇类，如糖，是一类重要的无毒和容易获得的原料化学品。因为它减少了浪费，并取代了目前的替代品，如使用有毒的有机卤化物，使用光化学和其他方法直接功能化酒精将包含许多绿色化学的原则。同样，能够与蛋白质和酶目标进行新型分子相互作用的新型化学型将在从传染病开始的药物发现工作中进行评估。该项目的基础发现将转化为市场机会：高效催化剂将在全球范围内商业化，生物活性先导化合物将被开发成候选药物。总的来说，环半硼酸作为开发新催化剂和药物化学型的平台是独特的，并且是有机硼催化和药物发现的理想选择。

This research program merges fundamental and applied science by targeting two related objectives of broad significance in green chemistry and drug discovery: the catalytic activation of nucleophilic functional groups (e.g., alcohols, amines, carboxylic acids), and the dearth of compound classes in drug discovery. To meet these objectives, Dr. Hall will study hemiboronic heterocycles, a class of stable boron-containing organic compounds for their potential ability to exchange their boron-oxygen bonds with alcohols and other nucleophilic (electron-rich) functional groups, and exploit these unique compounds as catalysts in useful chemical reactions and as scaffolds for drug discovery. To realize these applications, it is essential to first identify or design new boron-containing heterocycles that possess the ability to interact with nucleophilic groups in the desired conditions. Nucleophiles are electron-rich functional groups (e.g. alcohols, amines) that may displace other groups on electrophilic (electron-poor) atoms such as boron, through a "condensation" reaction that releases a water molecule. Thus, by using advanced mass spectrometry (MS) and NMR techniques, rapid, accurate, and general methods will be devised to probe the ability of common functional groups and aminoacid side chains to interact with hemiboronic acids. Using this knowledge, new catalysts will be designed to enable challenging synthetic transformations of interest in pharmaceutical chemistry, such as the direct functionalization of alcohols. Alcohols, such as sugars, are an important class of non-toxic and readily available feedstock chemicals. Because it decreases wastes and replaces current alternatives like the use of toxic organohalides, the direct functionalization of alcohols using photochemical and other methods will embrace many of the principles of green chemistry. Likewise, novel chemotypes capable of new types of molecular interactions with protein and enzyme targets will be evaluated in drug discovery efforts starting with infectious diseases.Fundamental discoveries from this program will be translated into market opportunities: efficient catalysts will be commercialized for global availability, and bioactive lead compounds will be developed into drug candidates. Overall the application of cyclic hemiboronic acids as a platform to develop new catalysts and drug chemotypes is unique, and is an ideal fit for this CRC in Organoboron for Catalysis and Drug Discovery.