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: 7275202
• 负责人: Mary P Watson
• 金额: $ 4.48万
• 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 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275202
• 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）：含氮丙啶的分子作为生物活性天然产物和通用合成中间体都具有重要意义。由于这些化合物的药物潜力以及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氮丙啶化方法。具体来说，该项目将使用易于制备的催化剂和易于获得的氮源，开发一种将易于获得的烯酮和不饱和酰亚胺一步转化为对映体富集的氮丙啶的方法。由于手性(salen)AI(III)催化剂在共轭加成反应中提供高对映选择性，因此这些催化剂将用于活化不饱和底物。一种双亲性氮源，例如氯胺-T，可以在一个合成步骤中形成两个 C-N 键。为了举例说明该反应的实用性，该氮丙啶化将用于制备合成中间体和具有抗白血病活性的小分子。这种形成对映体富集的氮丙啶的实用方法将促进新氮丙啶化合物的合成和生物测试，从而有可能产生新的药物。该提案旨在开发一种通用的一步法来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，例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。