Development of Efficient Carbon Carbon Bond Formations for Novel Se-, S-, and O-Heterocycle Synthesis

用于新型 Se-、S- 和 O-杂环合成的高效碳碳键形成的开发

• 批准号: 10412238
• 负责人: Fenghai Guo
• 金额: $ 12.81万
• 依托单位: WINSTON-SALEM STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10412238
• 关键词: Acylation; Alzheimer' s disease therapeutic; Bioflavonoid; Biological; Carbon; Chemistry; Communication; Complex; Coupling; Development; Funding; Generations; Heterocyclic Compounds; In Situ; Metals; Methods; Names; Natural Products; Nature; Oxygen; Pharmaceutical Preparations; Pharmacologic Substance; Process; Reaction; Reproduction; Research; Selenium; Sulfur; Synthesis Chemistry; Therapeutic; United States National Institutes of Health; analog; biological systems; catalyst; drug discovery; enolate; innovation; novel; novel strategies; oxidation; small molecule therapeutics; underrepresented minority student

NIH SuRE Project – Abstract Heterocycles account for more than 50% of all known organic compounds. Their rich activities in biological systems are important for pharmaceuticals and natural products. Among the top 200 brand name drugs, over 75% are heterocyclic compounds. In nature, heterocycles are active components for defense, communication, and reproduction. Low regioselectivities, low stereo-/enantioselectivities, lengthy synthetic sequences, and low overall yields in most multi-step syntheses make it extremely challenging to provide sufficient quantities of desired bioactive heterocycles for therapeutic purposes. This NIH SuRE proposal aims to develop and utilize highly selective metal catalyzed carbon carbon bond formation reactions that will lead to efficient synthesis of novel selenium, sulfur, and oxygen- containing heterocycles with rich biological activities. This proposal also aims to develop multicomponent coupling processes for rapid generation of functionality and complexity in heterocycles, a new selective merged asymmetric conjugate addition-acylation as well as a merged conjugate addition-oxidation strategy that will lead to the synthesis of new classes of bioactive selenium, sulfur- containing heterocycles. The proposed new C-C bond formations and multicomponent reactions will provide new opportunities for complex novel heterocycle synthesis. The metal-catalyzed conjugate addition of nucleophiles onto polyenic Michael acceptors is one of the most attractive and powerful C-C bond forming strategies for synthesis of relevant molecules, as it provides opportunity for sequential generation of two or more stereogenic centers in a straightforward fashion. The multicomponent reactions enabled by direct trapping of metal enolates could provide powerful transformations for the formation of multiple C-C bonds and chiral centers in a single pot. The resultant versatile heterocyclic subunits and trapping of the metal enolates in situ will provide excellent opportunities for new innovative approaches for novel complex heterocyle synthesis and drug discovery. Further elaboration of this chemistry will likely allow the first enantioselective synthesis of very important classes of heterocycles such as biselenoflavonoids, bithioflavonoids and bioactive biflavonoids, potential small molecule therapeutics for Alzheimer’s disease. This SuRE project is expected to significantly enhance and expand the research capacity towards a sustainable research excellence at WSSU, a HBCU.

NIH确定的项目 - 摘要 杂环占所有已知有机化合物的50％以上。他们丰富的活动 生物系统对于药品和天然产品很重要。在前200名品牌中 名称药物，超过75％是杂环化合物。在本质上，杂环组件是活性组件 防御，沟通和繁殖。较低的区域选择性，低立体声/对映选择性， 冗长的合成序列，大多数多步合成中的总收率较低，使其极为极佳 为治疗目的提供足够数量的所需生物活性杂环。 这项NIH肯定的建议旨在开发和利用高度选择性的金属催化碳碳 将导致新型硒，硫和氧气有效合成的键形反应 包含具有丰富生物学活性的杂环。该建议还旨在发展 多组分耦合过程，用于杂环快速生成功能和复杂性， 新的选择性合并不对称的共轭加成酰化以及合并的共轭 添加氧化策略将导致合成新的生物活性硒类 包含杂环。提出的新的C-C键形成和多组分反应将 为复杂的新型杂环合成提供了新的机会。金属催化的共轭物 在多元素迈克尔受体上添加核透明质是最有吸引力，最有力的C-C之一 键合成相关分子的策略，因为它为顺序的机会提供了机会 以直接的方式产生两个或多个立体代源中心。多组件 通过直接捕获金属烯醇启用反应可以为该反应提供强大的转换 在一个锅中形成多个C-C键和手性中心。最终的多功能杂环 亚基和捕获金属的原位将为新的创新提供绝佳的机会 新型复杂杂环合成和药物发现的方法。进一步阐述 化学可能会允许第一类非常重要的杂环的对映选择性合成 诸如双苯乙烯，Bithioflavonoids和生物活性双铁素，潜在的小分子 阿尔茨海默氏病的治疗剂。预计这个确保的项目将显着增强和 将研究能力扩展到HBCU WSSU的可持续研究卓越。