Oxygen Promoted Pd(II) Catalysis for Medicinal Chemistry

氧促进 Pd(II) 药物化学催化

• 批准号: 7086785
• 负责人: KYUNG W. JUNG
• 金额: $ 27.85万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7086785
• 关键词: alkenes; biological products; catalyst; chemical bond; chemical conjugate; chemical reaction; chemical structure; chemical synthesis; drug design /synthesis /production; drug discovery /isolation; oxygen; palladium; technology /technique development

DESCRIPTION (provided by applicant): As drug candidates, there are numerous bioactive natural products and synthetic compounds, which contain conjugated aryl and/or alkenyl moieties in their structures. To facilitate syntheses, we have embarked on the development of a new synthetic methodology to efficiently prepare such functional groups. This projected study extends our current synthetic protocol to a wide array of systems, to generate aryl-aryl, aryl-alkenyl, alkenyl-alkenyl, alkenyl-alkynyl bonds expeditiously. Since these functionalities are common in biologically active natural products and synthetic drug leads, our methodology will benefit synthetic and medicinal chemists by providing useful methods as well as crucial synthetic scaffolds. In this proposed project, we will study oxygen promoted Pd(ll) catalysis, reminiscent of the Heck reaction, to provide a complimentary method of preparing the aforementioned systems. While Heck chemistry utilizes oxidative addition to halides, our proposed protocol employs transmetallation of an aryl or alkenyl boronic acid. Due to the difference in mechanistic pathways, our conditions are mild and facile, offering an efficient alternative to the existing C-C bond forming tools. These transformations are achieved under base-free conditions, which are effective at room temperature with most substrates. Should the development of the current methodology become successful, this research will facilitate a lot of syntheses for drug discovery and process development. Besides, the oxidative Pd(ll) catalysis is an emerging field, and our successful development of the proposed methodology will strengthen this new field in organic chemistry. Additionally, the developed procedures are environmentally benign, thus the oxygen promoted catalysis can drastically reduce clean-up costs and avoid side reactions caused by metal salts and their by-products. As a result, this methodology will be applicable to large scale manufacturing, aiding in the drug development. We believe our novel technology will help to advance organic synthesis, process chemistry, and medicinal chemistry, culminating in drug discovery.

描述（由申请人提供）：作为候选药物，有许多具有生物活性的天然产物和合成化合物，其结构中含有共轭芳基和/或烯基部分。为了促进合成，我们开始开发一种新的合成方法来有效地制备此类官能团。这项预计的研究将我们目前的合成方案扩展到广泛的系统，以快速生成芳基-芳基、芳基-烯基、烯基-烯基、烯基-炔基键。由于这些功能在生物活性天然产物和合成药物先导物中很常见，因此我们的方法将通过提供有用的方法以及关键的合成支架使合成化学家和药物化学家受益。 在这个拟议的项目中，我们将研究氧促进的 Pd(II) 催化，让人想起 Heck 反应，以提供制备上述系统的补充方法。虽然 Heck 化学利用卤化物的氧化加成，但我们提出的方案采用芳基或烯基硼酸的金属转移。由于机械途径的差异，我们的条件温和且容易，为现有的 C-C 键形成工具提供了有效的替代方案。这些转化是在无碱条件下实现的，在室温下对大多数底物都是有效的。如果当前方法的开发取得成功，这项研究将促进药物发现和工艺开发的大量合成。此外，氧化Pd(II)催化是一个新兴领域，我们所提出的方法的成功开发将加强有机化学的这一新领域。 此外，所开发的程序对环境无害，因此氧气促进的催化可以大大降低清理成本，并避免金属盐及其副产物引起的副反应。因此，该方法将适用于大规模生产，有助于药物开发。我们相信我们的新技术将有助于推进有机合成、过程化学和药物化学，最终实现药物发现。