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: 7619478
• 负责人: Mary P Watson
• 金额: $ 1.8万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7619478
• 关键词: Amination; Antineoplastic Agents; Aziridines; Biological; Biological Factors; Biological Testing; Carbon; Chemicals; Face; Felis catus; Goals; Imides; Malignant Neoplasms; Medicine; Metals; Methods; Mitomycins; Nitrogen; One-Step dentin bonding system; Pharmacologic Substance; Preparation; Property; Reaction; Research; Source; 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多用途合成中间体都是重要的。由于这些化合物的药学潜力和目前缺乏一般的，一步的方法来形成它们的对映选择性，提出了一种新的催化，不对称氮杂环丙烷化方法。具体来说，该项目将开发使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酰亚胺一步转化为对映体富集的氮丙啶。因为手性（salen）Al（III）催化剂在共轭加成反应中提供高的对映选择性，所以这些催化剂将用于活化不饱和底物。两亲性氮源，如氯胺-T，将允许在一个合成步骤中形成两个C-N键。为了验证该反应的实用性，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，可能导致新药。该提案寻求开发一种用于制备含有碳原子和一个氮原子的三原子环的通用一步法。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，并用于制备具有生物活性的其他化学品。这种实用的方法将促进这些已知的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。