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。为了方便合成，我们已经着手开发一种新的合成方法来有效地制备这些官能团。这项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，我们的方法将通过提供有用的方法和关键的合成支架，使合成和药物化学家受益。