Catalytic, Asymmetric Aziridination using (Salen)metal Catalysts

描述(申请人提供)：含有氮杂环丙烷的分子作为具有生物活性的天然产物和用途广泛的合成中间体都具有重要意义。鉴于这类化合物的潜在药用价值，以及目前缺乏一步法选择性地合成这些化合物的一般方法，本文提出了一种新的催化不对称氮杂环化反应方法。具体地说，该项目将利用易于制备的催化剂和容易获得的氮源，将容易获得的烯类和不饱和亚胺一步转化为富含对映体的氮杂环丙烷。由于手性(Salen)Al(111)催化剂在共轭加成反应中具有很高的对映选择性，因此这些催化剂将被用来活化不饱和底物。双亲氮源，如氯胺-T，将允许在一个合成步骤中形成两个C-N键。为了说明这一反应的实用性，这一氮杂环化反应将被用于合成中间体和具有抗白血病活性的小分子。这种形成富含对映体的氮杂环丙烷的实用方法将有助于合成和生物测试新的氮杂环丙烷化合物，有可能导致新的药物。这项提议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，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物质。这种实用的方法将有助于合成这些已知的生物活性分子，并允许快速制备具有抗癌或其他药用性能的新化合物。

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.