Oxygen Promoted Pd(II) Catalysis for Medicinal Chemistry

氧促进 Pd(II) 药物化学催化

• 批准号: 7244353
• 负责人: KYUNG W. JUNG
• 金额: $ 27.05万
• 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/7244353
• 关键词: Alkenes; Benign; Biological Factors; Boronic Acids; Carbon; Catalysis; Chemistry; Closure; Complex; Condition; Coupling; Development; Facility Construction Funding Category; Felis catus; Ligands; Light; Metals; Methodology; Methods; Molecular; Object Attachment; Organic Chemistry; Organic Synthesis; Oxygen; Palladium; Pathway interactions; Pharmaceutical Chemistry; Pharmaceutical Preparations; Procedures; Process; Protocols documentation; Reaction; Research; Salts; Scheme; Side; Structure; Study Subject; System; Temperature; base; boronic acid; catalyst; cost; diene; drug development; drug discovery; functional group; new technology; novel; programs; scaffold; size; tool

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，存在许多生物活性天然产物和合成化合物，其在其结构中含有共轭芳基和/或烯基部分。为了促进合成，我们已经着手开发一种新的合成方法来有效地制备这样的官能团。这项计划的研究扩展了我们目前的合成方案，以广泛的系统，迅速产生芳基-芳基，芳基-烯基，烯基-烯基，烯基-炔基键。由于这些功能在具有生物活性的天然产物和合成药物中很常见，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而使合成和药物化学家受益。 在这个提议的项目中，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。虽然赫克化学利用氧化加成卤化物，我们提出的协议采用transmethalide的芳基或烯基硼酸。由于机理途径的差异，我们的条件温和而容易，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，这在室温下对大多数底物都是有效的。如果目前的方法学发展成功，这项研究将促进许多药物发现和工艺开发的合成。此外，氧化性Pd（II）催化是一个新兴领域，我们所提出的方法学的成功发展将加强有机化学中的这一新领域。 此外，开发的程序是环境友好的，因此氧促进的催化可以大大降低清洁成本，并避免由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，工艺化学和药物化学，最终在药物发现。

项目成果

Expeditious Enyne Construction from Alkynes via Oxidative Pd(II) Catalyzed Heck-Type Coupling.

• DOI: 10.1016/j.tetlet.2009.02.217
• 发表时间: 2009-05-20
• 期刊: TETRAHEDRON LETTERS
• 影响因子: 1.8
• 作者: Hadi, Victor;Yoo, Kyung Soo;Jeong, Min;Jung, Kyung Woon
• 通讯作者: Jung, Kyung Woon

Asymmetric intermolecular boron Heck-type reactions via oxidative palladium(II) catalysis with chiral tridentate NHC-amidate-alkoxide ligands.

• DOI: 10.1021/jo901977n
• 发表时间: 2010-01-01
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Yoo, Kyung Soo;O'Neill, Justin;Sakaguchi, Satoshi;Giles, Richard;Lee, Joo Ho;Jung, Kyung Woon
• 通讯作者: Jung, Kyung Woon

Chemoselective Three-Component Coupling via A Tandem Pd Catalyzed Boron-Heck and Suzuki Reaction.

通过串联 Pd 催化的硼赫克和铃木反应进行化学选择性三组分偶联。

• DOI: 10.1016/j.tetlet.2008.10.039
• 发表时间: 2008
• 期刊: Tetrahedron letters
• 影响因子: 1.8
• 作者: O'Neill,Justin;Yoo,KyungSoo;Jung,KyungWoon
• 通讯作者: Jung,KyungWoon

Air/Water-Stable Tridentate NHC-Pd Complex; Catalytic C-H Activation of Hydrocarbons via H/D Exchange Process in D(2)O.

空气/水稳定的三齿 NHC-Pd 络合物；通过 D(2)O 中的 H/D 交换过程催化碳氢化合物的 C-H 活化。

• DOI: 10.1002/adsc.200800698
• 发表时间: 2009-03-01
• 期刊: ADVANCED SYNTHESIS & CATALYSIS
• 影响因子: 5.4
• 作者: Lee, Joo Ho;Yoo, Kyung Soo;Park, Chan Pil;Olsen, Janet M.;Sakaguchi, Satoshi;Prakash, G. K. Surya;Mathew, Thomas;Jung, Kyung Woon
• 通讯作者: Jung, Kyung Woon

Oxygen-promoted palladium(II) catalysis: facile C(sp2)-C(sp2) bond formation via cross-coupling of alkenylboronic compounds and olefins.

• DOI: 10.1021/ol0483192
• 发表时间: 2004-10
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: C. H. Yoon;K. Yoo;S. Yi;R. Mishra;K. W. Jung