Stereoselective Heterocycle Synthesis via Zn(II) Promoted Metalloamination/Cyclization

通过 Zn(II) 促进金属胺化/环化立体选择性杂环合成

• 批准号: 9929898
• 负责人: THOMAS Stuart LIVINGHOUSE
• 金额: $ 3.82万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9929898
• 关键词: 1,2-Dimethylhydrazine; 14q; Acceleration; Address; Alkaloids; Amides; Appearance; Applications Grants; Area; Biological; Carbon; Chemistry; Complex; Cyclization; Deamination; Development; Disadvantaged; Event; Goals; Grant; Hydrogen; Intercept; Investigation; Ligands; Mediating; Metals; Methodology; Methods; Modification; Molecular Conformation; Nitrogen; Periodicity; Pharmaceutical Chemistry; Pharmacology; Piperazines; Preparation; Principal Investigator; Procedures; Process; Protocols documentation; Reaction; Reagent; Request for Applications; Research; Research Activity; Rest; Skeleton; Structure; Therapeutic; Tropanes; Zinc; base; chemical synthesis; comparative; cost; cost effective; diene; insight; novel; novel strategies; practical application; preference; programs; propadiene; prospective; small molecule

PROJECT SUMMARY The elucidation of new, highly stereocontrolled reactions for the construction of carbon–nitrogen and carbon-carbon bonds remains a central goal of chemical synthesis. Over the years, various discoveries in this area have enabled the efficient preparation of a wide variety of important medicinals that have benefited humanity. This grant application requests support for the Principal Investigator's new projects in the area of organozinc(II)-promoted heterocycle synthesis. The present application emphasizes the discovery and synthetic application of a new and potentially powerful intramolecular C- N/C-Zn bond forming cascade involving the addition of functionalized zinc amides, derived from N,N- dimethylhydrazines, to allenes, dienes, enynes, vinylcyclopropanes and vinylcyclobutanes. We believe this method will receive considerable utilization as a vehicle for the stereocontrolled synthesis of biologically relevant small molecules. The application of the new chemistry discovered during the proposed grant period should be readily applicable to the synthesis of numerous stereochemically rich heterocycles of pharmacological significance. The research program described in this grant application is expected to provide valuable insight into new reaction types that should serve to elucidate specific factors that are critical to the development of consecutive intramolecular C-N/C-Zn (and thus: C-N/C-Electrophile) bond formation in the context of stereocontrolled small molecule synthesis.

项目摘要 阐明新的，高度立体控制的反应用于碳 - 氮的构建 和碳碳键仍然是化学合成的核心目标。多年来，各种各样 该领域的发现使各种重要医疗有效地准备了 受益于人类。该赠款申请要求对首席调查员的支持 促成杂环合成（II）领域（II）领域的新项目。本申请 强调新的且潜在强大分子内C-的发现和合成应用 N/c-Zn键形成级联 二甲基氢嗪，到艾伦，二烯，enynes，乙烯基丙烷和乙烯基甲丙烷。我们相信 该方法将获得考虑利用作为立体控制合成的工具 生物学相关的小分子。 在拟议的赠款期间发现的新化学反应的应用应为 容易适用于众多立体化学上富含药物的杂环的合成 意义。预计本赠款申请中描述的研究计划将提供有价值的 对新反应类型的见识，这些反应类型应阐明对特定因素至关重要的特定因素 奉献的分子内C-N/C-ZN（因此：C-N/C-电动噬菌体）在 立体控制的小分子合成的背景。

项目成果

Sulfenate Esters of Simple Phenols Exhibit Enhanced Activity against Biofilms.

简单酚的磺酸酯表现出增强的抗生物膜活性。

• DOI: 10.1021/acsomega.9b04392
• 发表时间: 2020
• 期刊: ACS omega
• 影响因子: 4.1
• 作者: Walsh,DanicaJ;Livinghouse,Tom;Durling,GregM;Chase-Bayless,Yenny;Arnold,AdrienneD;Stewart,PhilipS
• 通讯作者: Stewart,PhilipS

Efficient reductions of dimethylhydrazones using preformed primary amine boranes

• DOI: 10.1080/00397911.2021.2008449
• 发表时间: 2021-12-06
• 期刊: SYNTHETIC COMMUNICATIONS
• 影响因子: 2.1
• 作者: Frabitore, Christian;Lepeule, Jerome;Robinson, William C.
• 通讯作者: Robinson, William C.