Phase II Environmentally greener, efficient, and safe synthetic platform for the

二期 更环保、更高效、更安全的合成平台

• 批准号: 8141298
• 负责人: Paul Matthew Herrinton
• 金额: $ 47.54万
• 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 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8141298
• 关键词: Address; Area; Benign; Boron; Boronic Acids; Carbon; Cataloging; Catalogs; Characteristics; Chemicals; Chemistry; Client; Development; Disease; Drug Compounding; Drug Costs; Esters; Feedback; Food Supply; Grant; Hepatoprotective Agent; Imidazole-Pyrazole; In Situ; Industrial fungicide; Industry; Insecta; Iridium; Kilogram; Laboratories; Licensing; Malaria; Marketing; Medicine; Methodology; Methods; Michigan; Molecular; Optruma; Outcome; Oxazoles; Pesticides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenols; Process; Production; Provider; Pyrazines; Pyrimidines; Quality of life; Reaction; Rest; Route; Silymarin; Technology; Universities; base; catalyst; combat; cost; drug candidate; drug discovery; functional group; hydroxypyridines; interest; new technology; novel; novel strategies; oxidation; phase 1 study; practical application; professor; public health relevance; pyridine; quinoline; scale up; success

DESCRIPTION (provided by applicant): We propose to continue expanding the study of iridium-catalyzed aromatic C-H activation/borylation in concert with other chemical conversions as a new approach to currently inaccessible chemical building blocks that will be highly useful for variety of practical applications, including pharmaceutical, agro-chemical, materials and fine chemical development. The mildness of the Ir-catalysts and the reaction conditions under which they operate, allows for the borylation of arenes containing a variety of functional groups. Given this substrate tolerance, a wide range of subsequent same-pot reactions is possible, and currently under development. Our newly invented process that "telescopes" C-H activation/borylation with oxidations serves as a prime example of this ability to couple borylation with other chemical transformations in an efficient, scaleable way. This process provides rapid and unique access to new and highly functionalized phenolic building blocks that are currently commercially unavailable or accessible only by protracted, costly, and otherwise unattractive routes. Phenols are commercially important compounds that are extensively utilized, 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. Based on the successful completion of Phase I objectives and industry feedback from BoroPharm's growing client base, the following specific aims will be addressed in this Phase II proposal: 1. Expand the portfolio of borylated pyridine derivatives and add quinolines, pyrazines, pyrimidines, diazenes, imidazoles, pyrazoles, oxazoles, etc. Produce oxidized products (e.g. hydroxyquinolines) where applicable. 2. Explore new boron technologies including the formation and utilization of trifluoroborate, triolate, and MIDA derivatives. 3. Augment the phenol portfolio to make more previously unreported products available. Increase the scale to produce kilogram quantities. 4. Expand upon additional transformations of aryl boronates in the portfolio, and to produce new products where the carbon-boron bonds are either transformed or retained. 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 the next phase of a 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. This project is a continuation of a phase I grant that succeeded with positive outcomes. Herein, we will expand upon the breadth, scope and scale of the chemical platform and expand on the synthesis of novel and useful pharmaceutical building blocks.

描述（由申请人提供）：我们建议继续扩展对虹膜催化的芳香族C-H激活/体内化的研究，以与其他化学转化率一起作为一种新方法，作为当前难以接近的化学构建块的一种新方法，这些方法将对多种实际应用，包括药物，农业化学，材料，材料和细化的化学物质和美化化学化学物质。 IR催化剂的温和性及其操作的反应条件允许含有各种官能团的竞技场的气体化。鉴于这种底物公差，可能会发生多种随后的同一罐反应，并且目前正在开发中。我们新发明的工艺“望远镜” C-H激活/透明化的氧化是这种能力，即以有效的，可伸缩的方式将boryation与其他化学转化搭配到其他化学转化的能力。此过程为新的，高度功能化的酚类构建块提供了快速而独特的访问，这些企业构建块目前在商业上无法获得或仅通过旷日持久，昂贵且没有吸引力的路线而访问。酚是广泛使用的商业重要化合物，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。基于Boropharm不断增长的客户群的I阶段目标和行业反馈的成功完成，将在本II期提议中解决以下具体目标：1。扩展硼丁吡啶衍生物的组合，并添加喹啉，吡嗪，吡嗪，吡啶胺，吡啶并生产吡a，吡唑，氧化氧气，氧气，氧气，氧气，氧气，氧气，氧气，氧化物等。适用的地方。 2。探索新的硼技术，包括三氟化，三明治和MIDA衍生物的形成和利用。 3。增加苯酚投资组合以使更多以前未报告的产品可用。增加量表以产生千克数量。 4。扩展投资组合中芳基硼酸酯的其他转化，并生产新产品，其中碳 - 波朗键要么被转化或保留。 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，我们建议开发新的技术的下一阶段，以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。该项目是I阶段赠款的延续，并取得了积极成果。在此，我们将扩展化学平台的宽度，范围和规模，并扩展新型和有用的药物构建块的合成。