Advancing the Utility of Organocatalysis in the Synthesis of Therapeutic Agents

推进有机催化在治疗药物合成中的应用

• 批准号: 7613507
• 负责人: Stacey E Brenner-Moyer
• 金额: $ 11.78万
• 依托单位: BROOKLYN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-11 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613507
• 关键词: Area; Biological Factors; CCL7 gene; Catalysis; Claisen rearrangement; Data; Dependence; Development; Disease; Effectiveness; Environment; Extramural Activities; Fostering; Foundations; Funding; Goals; Hand; Health; Human; Hydrogen Bonding; Laboratories; Laboratory Research; Lead; Mentors; Metals; Methods; Mission; Mole the mammal; Molecular; Outcome; Pharmacologic Substance; Pilot Projects; Principal Investigator; Process; Production; Publishing; Reaction; Reporting; Research; Research Personnel; Resource Sharing; Students; Sulfonamides; System; Testing; Therapeutic; Therapeutic Agents; Training; Transition Elements; Underrepresented Minority; Work; base; career; catalyst; college; design; drug discovery; improved; innovation; novel; programs; research and development; scaffold; skills; small molecule; therapeutic development; user-friendly

DESCRIPTION (provided by applicant): There is a need for improved organocatalysts and new organocatalytic processes to realize the potential of organocatalysis to streamline the research and development of small molecules as therapeutic leads. The long-term goal is to use organocatalysis in the synthesis of small molecules that treat human illnesses. The objective of this pilot project is to develop improved organocatalysts and new organocatalytic reactions. There are two hypotheses that underlie this research: (1) that acidic double hydrogen bond donors with a rigid achiral scaffold will act as improved organocatalysts, and (2) that new organocatalytic processes can be adapted from reactions catalyzed by bidentate coordination of metals to substrates. The rationale for the proposed research is that once improved organocatalysts and new organocatalytic processes are developed, they can be exploited in the synthesis of small molecules of medicinal value. As this research proposes new methods which can be employed in the synthesis of compounds that can improve human health, it pertains to NIH's mission of fostering the development and application of new strategies for improving health. The hypotheses were generated from published data regarding the efficacy, rational design, and mode of action of related organocatalysts, and will be tested by two specific aims: (1) to identify a new molecular framework for improved organocatalyst systems; and 2) to adapt intramolecular metal-catalyzed reactions as new organocatalytic processes. For both aims, proposed and existing organocatalysts will be synthesized and screened for effectiveness in established and proposed organocatalytic reactions. The proposed research will render organocatalysis more competitive with conventional transition metal catalysis. This is significant because it will advance the utility of organocatalysis, a safer, cheaper and procedurally simpler alternative to transition metal catalysis, in the synthesis of medicinal compounds. The proposed research aims to improve the efficiency and versatility of organic compounds as reaction catalysts or organocatalysts. Despite the fact that organocatalysts are safer, cheaper, and more user-friendly than metal catalysts, the latter are more commonly employed to synthesize compounds of medicinal value because they are more efficient and more versatile. The proposed research will thus help to establish organocatalysts as a superior alternative to metal catalysts for the synthesis of medicinal compounds.

描述（由申请人提供）：需要改进的有机催化剂和新的有机催化方法来实现有机催化的潜力，以简化作为治疗先导物的小分子的研究和开发。长期目标是利用有机催化合成治疗人类疾病的小分子。该试点项目的目标是开发改进的有机催化剂和新的有机催化反应。这项研究有两个假设：（1）具有刚性非手性支架的酸性双氢键供体将充当改进的有机催化剂，（2）新的有机催化过程可以适应金属与底物的二齿配位催化的反应。这项研究的基本原理是，一旦开发出改进的有机催化剂和新的有机催化工艺，它们就可以用于合成具有药用价值的小分子。由于这项研究提出了可用于合成可改善人类健康的化合物的新方法，因此它符合 NIH 促进改善健康新策略的开发和应用的使命。 这些假设是根据有关有机催化剂的功效、合理设计和作用模式的已发表数据产生的，并将通过两个具体目标进行测试：（1）确定改进有机催化剂系统的新分子框架； 2）将分子内金属催化反应作为新的有机催化过程。为了这两个目标，将合成提议的和现有的有机催化剂，并筛选其在已建立的和提议的有机催化反应中的有效性。拟议的研究将使有机催化比传统的过渡金属催化更具竞争力。这很重要，因为它将促进有机催化在药物化合物合成中的应用，有机催化是过渡金属催化的一种更安全、更便宜且程序更简单的替代品。 拟议的研究旨在提高有机化合物作为反应催化剂或有机催化剂的效率和多功能性。尽管有机催化剂比金属催化剂更安全、更便宜、更用户友好，但后者更常用于合成具有药用价值的化合物，因为它们更有效且用途更广泛。因此，拟议的研究将有助于建立有机催化剂作为药物化合物合成中金属催化剂的优越替代品。