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激活/植物与其他化学事件的组合，作为一种新型和非常有用但目前无法访问的药物开发的构建块。它们操作的IR催化剂和反应条件的温和度允许含有各种官能团的竞技场。鉴于这种底物的耐受性，随后的同一池反应的范围也被耐受。新发明的流程“望远镜” C-H激活/氧化剂具有氧化功能，可以独特地访问新的和高度功能的酚类构建块，这些基础在商业上不可用，或者只能通过旷日持久的，昂贵的且没有吸引力的途径来访问。酚是具有广泛商业重要性的重要化合物，尤其是在药物发现，开发和制造领域。即使有一系列生产方法，仍然有许多相对简单的示例，其中已建立的合成器的长度和/或较低的收益率用于实际使用。在此提案中，Boropharm的目的是通过专有技术的商业开发来打击这些困难，这些技术已被专门许可获得Boropharm，Inc.。特别是，Boropharm旨在验证虹膜催化的芳族芳香化/氧化，作为一门商业途径，可作为药品相关的现象和羟基二氧化异物衍生物的商业途径。使用现代合成化学的工具，将实现以下目标：1。评估Boropharm苯酚提供对100 g苯酚产品的可伸缩性的评估。 2。优化载体催化剂/配体组合和负载。 3。评估氧化剂对苯酚产量的影响。 4。硼植物苯酚组合的扩展，包括氟和氰基取代的苯酚。 5。将载体氧化扩展到吡啶和喹啉底物。 公共卫生相关性：新药的发明在很大程度上取决于化学家从分子构建基块中组装独特化合物的能力。在这方面，新的药品要求新的建筑块，而成本较低的药物将需要对这些主要中间体的效率更高且对环保的路线。在此，我们建议开发新技术来创建独特而多功能的化学构建块，其发明将有助于发现和开发新药物。