Catalytic, Asymmetric Aziridination using (Salen)metal Catalysts

使用 (Salen) 金属催化剂进行催化不对称氮丙啶化

• 批准号: 7383897
• 负责人: Mary P Watson
• 金额: $ 4.68万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383897
• 关键词: Amination; Antineoplastic Agents; Aziridines; Biological; Biological Factors; Biological Testing; Carbon; Chemicals; Face; Facility Construction Funding Category; Felis catus; Goals; Imides; Malignant Neoplasms; Medicine; Metals; Methods; Mitomycin; Nitrogen; Object Attachment; One-Step dentin bonding system; Pharmacologic Substance; Preparation; Property; Reaction; Research; Source; aziridine; carbonyl compound; catalyst; chloramine-T; enolate; leukemia; salen; small molecule

DESCRIPTION (provided by applicant): Aziridine-containing molecules are significant both as biologically active natural products and as versatile synthetic intermediates. Because of the pharmaceutical potential of these compounds and the current lack of general, one-step methods to form them enantioselectively, a new catalytic, asymmetric aziridination method is proposed. Specifically, this project will develop a one-step transformation of readily accessible enones and unsaturated imides into enantioenriched aziridines using easily prepared catalysts and readily available nitrogen sources. Because chiral (salen)AI(lll) catalysts provide high enantioselectivity in conjugate addition reactions, these catalysts will be used to activate the unsaturated substrates. An ambiphilic nitrogen source, such as Chloramine-T, will allow both C-N bonds to be formed in one synthetic step. To exemplify the utility of this reaction, this aziridination will be used to make both synthetic intermediates and a small molecule with anti-leukemia activity. This practical method to form enantioenriched aziridines will facilitate synthesis and biological testing of new aziridine compounds, potentially leading to new medicines. This proposal seeks to develop a general, one-step method for the preparation of three-atom rings containing carbon atoms and one nitrogen atom. These rings are present in medically important compounds such as the anti-cancer drug mitomycin C and are used in the preparation of other chemicals with biological activity. This practical method will facilitate the synthesis of these known biologically active molecules as well as allow the rapid preparation of new compounds with anti-cancer or other medicinal properties.

描述（由申请人提供）：含氮吡啶分子是重要的生物活性天然产物和多功能合成中间体。由于这些化合物具有潜在的制药潜力，而且目前缺乏对映选择性形成它们的通用一步法，因此提出了一种新的催化不对称叠氮化方法。具体来说，该项目将利用易于制备的催化剂和易于获得的氮源，将容易获得的烯酮和不饱和亚胺一步转化为对映体富集的氮嘧啶。由于手性（salen）AI（ll）催化剂在共轭加成反应中具有很高的对映选择性，因此这些催化剂将用于激活不饱和底物。两亲性氮源，如氯胺- t，将允许两个碳氮键在一个合成步骤中形成。为了举例说明这种反应的效用，这种叠氮化将用于合成中间体和具有抗白血病活性的小分子。这种生成富对映体氮化吡啶的实用方法将促进新的氮化吡啶化合物的合成和生物学测试，有可能开发出新药。本提案旨在开发一种通用的一步法，用于制备含有碳原子和一个氮原子的三原子环。这些环存在于医学上重要的化合物中，如抗癌药物丝裂霉素C，并用于制备其他具有生物活性的化学品。这种实用的方法将促进这些已知生物活性分子的合成，并允许快速制备具有抗癌或其他药用特性的新化合物。