SINGLET OXYGEN IN THE SYNTHESIS OF BIOACTIVE MOLECULES

生物活性分子合成中的单线态氧

• 批准号: 3484173
• 负责人: HARRY H WASSERMAN
• 金额: $ 19.24万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3484173
• 关键词: alkynes; biological products; drug design /synthesis /production; genetic manipulation; indoles; lactams; lactones; oxazoles; oxidation; photochemistry; polypropylenes; polyvinyls; pyrroles; singlet oxygen

In our proposed research we will aim to extend the applicability of singlet oxygen reactions in organic synthesis by photooxidation studies on functional units which react efficiently and specifically with this highly electrophilic excited species. Singlet oxygen is a remarkable oxidizing gent which is readily available, inexpensive and specific in its action. Its applications in synthesis have yet to be fully exploited by organic chemists. In our further work, we hope to extend the scope and versatility of these reactions in the formation of products of medicinal interest. Specifically, we will continue our studies on the singlet oxygen- promoted conversion of oxazoles to triamides as a route to medium-size as well as macrocyclic lactones and lactams. In particular, the reaction sequence involving nucleophilic substitution on the oxazole ring, followed by photooxidation to generate an activated carboxylate, effectively employs the oxazole template as a carbonyl-1,1-dipole (+C=O) equivalent. Using the singlet oxygen-enamine cleavage reaction to generate vicinal tricarbony derivates, we will explore new ways of introducing this highly electrophilic unit into organic systems by appending acceptor sites such as vinyl, acetylenic and cyclopropyl residues to the tricarbony aggregate. In one application, this procedure will provide new routes to intermediates in the indole alkoloid field. The reactions of singlet oxygen with hydroxypyrroles and other pyrrole derivatives will be investigated as a practical means of introducing oxygenated functionality at specific sites in organic molecules. Applications in the synthesis of intermediates related to mytomycin, swainsonine, castanospermine and the pyrrolizidine alkaloids will be examined. Pyrrole photooxidation will also be studied as a synthetic (and possible biomimetric) route to naturally-occurring plant products.

在我们提出的研究中，我们的目标是扩展其适用性 通过光氧化研究有机合成中的单线态氧反应 与此有效且特异性反应的功能单元 高度亲电激发的物种。 单线态氧是一个了不起的 氧化剂是一种容易获得、廉价且具有特异性的氧化剂 它的行动。 其在合成方面的应用尚未完全 被有机化学家利用。 在我们的进一步工作中，我们希望能够扩展 这些反应形成的范围和多功能性 具有药用价值的产品。 具体来说，我们将继续研究单线态氧- 促进恶唑转化为三酰胺作为中等尺寸的途径 以及大环内酯和内酰胺。 特别是， 涉及恶唑亲核取代的反应顺序 环，然后通过光氧化生成活化的羧酸盐， 有效地利用恶唑模板作为羰基-1,1-偶极子 (+C=O) 相等的。 利用单线态氧-烯胺裂解反应生成邻位 三碳衍生物，我们将探索引入这种衍生物的新方法 通过附加受体将高度亲电单元引入有机系统 位点，例如乙烯基、炔属和环丙基残基 三羰基聚集体。 在一个应用程序中，此过程将提供 吲哚生物碱领域中间体的新路线。 单线态氧与羟基吡咯及其他吡咯的反应 将研究衍生品作为引入的实际手段 有机分子中特定位点的氧化功能。 在丝裂霉素相关中间体合成中的应用， 苦马豆碱、栗精胺和吡咯里西啶生物碱将 检查了。 吡咯光氧化也将作为一种合成方法进行研究 （以及可能的生物模拟）天然植物产品的途径。