"New Synthetic Methods and Applications of Boronic Acids in Stereoselective Cross-Coupling, Catalysis, and Chemical Biology"

“硼酸的新合成方法及其在立体选择性交叉偶联、催化和化学生物学中的应用”

• 批准号: 203287-2012
• 负责人: Hall, Dennis
• 金额: $ 10.2万
• 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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=593800
• 关键词: New; Synthetic; Methods; Applications; Boronic

With discoveries like 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 non-toxic synthetic compounds that have undergone huge developments only over the past two decades. Continued growth in the synthetic and biological applications of boronic acids 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: Our interest in stereochemistry (the selective preparation of "mirror image" forms of chiral (unsymmetrical) compounds, which is of critical importance in the pharmaceutical industry) will focus on the challenging cross-coupling of saturated mono-, di-, and tri-boryl compounds. Catalytic cross-couplings are a Nobel Prize winning (2010) class of chemical reactions that have had a huge impact as a way to generate novel organic molecules in the pharmaceutical industry. Stereoselective cross-couplings of saturated molecules could help streamline the synthesis of chiral drugs. 2. New catalytic processes: We will examine new applications of boronic acids as mild and 'green' catalysts for aromatic alkylations via alcohol activation. 3. Novel bioorthogonal conjugation chemistry: Boronate formation with rigid diols offers a rare case of spontaneous dehydrative condensation in water that is bioorthogonal, and it does not require toxic catalysts. We will optimize a 'click' conjugation system that could become a system of choice in chemical biology and surface sciences. 4. Functionalization of natural materials: There is huge interest in maximizing the value of renewable natural resources found in Canada. Nanocrystalline cellulose (NCC) is a wooden biomass by-product of the pulp and paper industry. One challenge with this intriguing material is its surface functionalization, especially to render it more hydrophobic to expand its applications. Our knowledge of boronic acid chemistry will be exploited to design agents for the controlled and reversible functionalization of NCC.

随着药物、杀虫剂、聚合物和食品添加剂等的发现，有机合成成为一门强大的科学，帮助我们的现代社会在过去的世纪中大幅提高了预期寿命和生活水平。硼酸是稳定且无毒的合成化合物，仅在过去二十年中才经历了巨大的发展。硼酸的合成和生物学应用的持续增长只有在其性质和反应性的明智探索的支持下才会发生。根据这一观点，将在以下方向开展新的项目：1.合成方法学开发：我们对立体化学（手性（不对称）化合物的“镜像”形式的选择性制备，这在制药工业中至关重要）的兴趣将集中在饱和单，二和三硼基化合物的具有挑战性的交叉偶联上。催化交叉偶联是一种获得诺贝尔奖（2010年）的化学反应，作为制药工业中产生新型有机分子的一种方式，具有巨大的影响。饱和分子的立体选择性交叉偶联有助于简化手性药物的合成。2.新的催化工艺：我们将研究新的应用硼酸作为温和的和“绿色”催化剂的芳香族烷基化通过醇活化。3.新的生物正交共轭化学：与刚性二醇的硼酸盐形成提供了一种罕见的情况下，在水中的自发脱水缩合是生物正交的，它不需要有毒的催化剂。我们将优化一个“点击”共轭系统，它可能成为化学生物学和表面科学的首选系统。4.天然材料的功能化：人们对最大限度地提高加拿大可再生自然资源的价值有着巨大的兴趣。纳米晶体纤维素（NCC）是纸浆和造纸工业的木质生物质副产品。这种有趣的材料的一个挑战是其表面功能化，特别是使其更具疏水性以扩大其应用。我们的硼酸化学知识将被利用来设计NCC的可控和可逆官能化试剂。