Environmentally greener, efficient, and safe synthetic platform for the productio

更环保、高效、安全的生产合成平台

• 批准号: 7538776
• 负责人: Paul Matthew Herrinton
• 金额: $ 15.32万
• 依托单位: BOROPHARM, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538776
• 关键词: Area; Benchmarking; Benign; Boron; Boronic Acids; Characteristics; Chemicals; Chemistry; Condition; Development; Disease; Drug Compounding; Drug Costs; Esters; Evaluation; Event; Food Supply; Hepatoprotective Agent; In Situ; Industrial fungicide; Insecta; Iridium; Laboratories; Licensing; Ligands; Malaria; Marketing; Medicine; Methods; Michigan; Molecular; Object Attachment; Optruma; Oxidants; Pesticides; Pharmaceutical Preparations; Pharmacologic Substance; Phenols; Process; Production; Public Health; Quality of life; Range; Reaction; Research; Rest; Route; Scientist; Silymarin; Staging; Synthesis Chemistry; Technology; Universities; base; boronic acid; catalyst; cost; drug discovery; expectation; functional group; hydroxypyridine; hydroxypyridines; interest; new technology; novel; novel strategies; oxidation; professor; pyridine; quinoline; scale up; tool

DESCRIPTION (provided by applicant): We propose to study the combination of Ir-catalyzed aromatic C-H activation/borylation with other chemical events as a new approach to novel and highly useful, but currently inaccessible building blocks for pharmaceutical development. The mildness of the Ir-catalysts and reaction conditions under which they operate allows the borylation of arenes containing a variety of functional groups. Given this substrate tolerance, wide ranges of subsequent same-pot reactions are also tolerated. Newly invented processes that "telescope" C-H activation/borylation with oxidations allow unique access to new and highly functionalized phenolic building blocks that are commercially unavailable or only accessible by protracted, costly, and otherwise unattractive routes. Phenols are important compounds with broad commercial importance, especially in the area of drug discovery, development, and manufacture. Even with an array of methods for their production, there are still many relatively simple examples where the established syntheses are prohibitively long and/or low yielding for practical use. In this proposal BoroPharm aims to combat these difficulties through the commercial development of proprietary technology that has been exclusively licensed to BoroPharm, Inc. Specifically, BoroPharm aims to validate iridium-catalyzed aromatic borylation/oxidation as a commercial route to pharmaceutically relevant phenols and hydroxypyridines. Using the tools of modern synthetic chemistry, the following objectives will be pursued: 1. Assessment of scalability of BoroPharm's phenol offerings to 100 g of phenol products. 2. Optimization of borylation catalyst/ligand combinations and loadings. 3. Evaluation of the effects of oxidant on phenol yield. 4. Expansion of BoroPharm's phenol portfolio including fluoro and cyano substituted phenols. 5. Extension of borylation oxidation to pyridine and quinoline substrates. PUBLIC HEALTH RELEVANCE: The invention of new drugs rests heavily on the chemist's ability to assemble unique compounds from molecular building blocks. In this regard, new pharmaceuticals call for new building blocks, while lower cost drugs will require more efficient and environmentally friendly routes to these key intermediates. Herein we propose to develop novel technology for the creation of unique and versatile chemical building blocks, the invention of which will aid the discovery and development of new medicines.

描述（由申请人提供）：我们建议研究 Ir 催化的芳香族 C-H 活化/硼化与其他化学事件的组合，作为一种新方法，用于开发新颖且非常有用但目前无法获得的药物开发构建模块。 Ir 催化剂的温和性及其运行的反应条件允许含有各种官能团的芳烃的硼基化。考虑到这种底物耐受性，也可以耐受大范围的后续同锅反应。新发明的通过氧化“望远镜”C-H活化/硼基化的方法可以独特地获得新的和高度功能化的酚类结构单元，这些结构单元在商业上无法获得或只能通过长期、昂贵且没有吸引力的途径获得。苯酚是具有广泛商业重要性的重要化合物，特别是在药物发现、开发和制造领域。即使有一系列的生产方法，仍然存在许多相对简单的例子，其中所建立的合成对于实际使用来说太长和/或产率低。在这项提案中，BoroPharm 旨在通过专有技术的商业开发来解决这些困难，该技术已独家授权给 BoroPharm, Inc.。具体来说，BoroPharm 的目标是验证铱催化的芳香硼化/氧化作为制药相关酚类和羟基吡啶的商业途径。使用现代合成化学工具，将实现以下目标： 1. 评估 BoroPharm 苯酚产品至 100 克苯酚产品的可扩展性。 2.硼化催化剂/配体组合和负载量的优化。 3、评价氧化剂对苯酚收率的影响。 4. 扩大BoroPharm 的苯酚产品组合，包括氟代和氰基取代的苯酚。 5.将硼化氧化扩展到吡啶和喹啉底物。 公共健康相关性：新药的发明在很大程度上取决于化学家从分子构件组装独特化合物的能力。在这方面，新药物需要新的构建模块，而成本较低的药物将需要更有效、更环保的途径来获取这些关键中间体。在此，我们建议开发新技术来创建独特且多功能的化学构件，其发明将有助于新药的发现和开发。