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C-H活化/硼化与其他化学事件的结合，作为一种新的、非常有用的、但目前难以获得的药物开发基础的新方法。ir催化剂的温和性及其操作的反应条件允许含有多种官能团的芳烃的硼化。鉴于这种底物耐受性，随后的大范围同锅反应也可以耐受。新发明的“望远镜”C-H活化/氧化硼化工艺允许独特的新的和高度功能化的酚类构建块，这些构建块在商业上不可用或只能通过长期、昂贵和其他不吸引人的途径获得。酚类化合物是具有广泛商业价值的重要化合物，特别是在药物发现、开发和制造领域。即使有了一系列的方法来生产它们，仍然有许多相对简单的例子，在这些例子中，已经建立的合成方法对于实际使用来说过于漫长和/或产量低。在该提案中，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旨在验证铱催化的芳香硼化/氧化作为制药相关酚和羟基吡啶的商业途径。使用现代合成化学的工具，将追求以下目标：评估百康苯酚产品的可扩展性至100克苯酚产品。2. 硼化催化剂/配体组合及负载的优化。3. 氧化剂对苯酚产率影响的评价。4. 扩大渤药业的苯酚产品组合，包括氟和氰基取代苯酚。5. 硼化氧化扩展到吡啶和喹啉底物。