Boronic Acid Chemistry as a Modern Platform in Catalysis, Stereocontrolled Synthesis and Bioconjugation

硼酸化学作为催化、立体控制合成和生物共轭的现代平台

• 批准号: RGPIN-2017-05086
• 负责人: Hall, Dennis
• 金额: $ 10.13万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=693517
• 关键词: Boronic; Acid; Chemistry; Modern; Platform

With discoveries like pharmaceutical drugs, insecticides, polymers, and food additives, organic synthesis stands as a powerful science that helped our modern society enjoy a dramatic increase in life expectancy and standard of living in the past century. Boronic acids are stable and relatively non-toxic boron-containing organic compounds that have undergone huge developments only over the past two decades. Continued growth in their synthetic and biological applications will occur only if supported by a judicious exploration of their properties and reactivity. With this view, new projects will be undertaken in the following directions: 1. Synthetic methodology development, with a focus on stereoselective synthesis to enable the selective preparation of "mirror image" forms of chiral (unsymmetrical) compounds, an endeavor of critical importance in the pharmaceutical industry. To this end, we will address the challenge of preparing highly functionalized heteroatom-containing chiral alkylboronic esters, and optimize methods for their stereoselective catalytic cross-coupling as a means to streamline the synthesis of chiral drugs. 2. New catalytic processes: We will examine new applications of boronic acids as mild and 'green' catalysts for direct elimination and substitutions of readily available alcohols, thus bypassing the use of toxic alkyl halides in these important classes of reactions. The discovery of borate-based catalytic leaving groups for primary alcohols is a high-risk-high-reward objective that would address many green chemistry “priority areas” of pharmaceutical chemistry. 3. Novel bioorthogonal conjugation chemistry with native peptides: Boronate formation with rigid diols provides a bioorthogonal “click” reaction with non-toxic components. Using two different approaches: phage display selection of peptide libraries, and rational design of heteropolycyclic boronate adducts, we will identify short and unique natural peptide sequences with a tight binding affinity to ortho-formyl arylboronic acids. Such peptides could be incorporated readily into a protein of interest due to its genetic encodability, thus providing a simple, fast and biocompatible conjugation system with labeled boronic acids that would be of great utility for investigating protein function in living systems in real time.

伴随着药物，杀虫剂和食物添加剂等发现，有机合成就像现代社会一样，在过去的中心享有人们的期望和生活水平的急剧增长。化合物在过去的两种巨大的巨大巨大合成和逻辑应用中，将在以下方向上进行探索它们的特性和反应性。至关重要的是，我们将解决高度功能的杂原烷基烷基酯酯催化交叉偶联以简化手性药物的合成，以直接消除和催化剂，以使杂种烷基烷基酯的挑战。这些重要类别的反应类别。刚性二醇提供了非毒性成分的生物性“点击”反应。由于其遗传编码性，因此提供了一个简单，快速和生物相容性的连接系统，并标有标记的硼酸酸，这些醇酸将是用于实时研究蛋白质功能的蛋白质功能。