Novel Syntheses of Heterocyclic and Aromatic Compounds

杂环和芳香族化合物的新合成

• 批准号: 6766138
• 负责人: JAMES W HERNDON
• 金额: $ 12.28万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6766138
• 关键词: alkenes; alkynes; aziridines; benzofurans; carbene; carbonyl group; chemical conjugate; chemical reaction; chemical structure function; chemical synthesis; drug design /synthesis /production; epoxides; heavy metals; heterocyclic compounds; intermolecular interaction; isoquinolines; morphine; pyrones; pyrroles; steroids

The research in this proposal focuses on the development of methods for the preparation of medicinally important heterocyclic ring systems and carbocyclic ring systems. The methodology utilizes the coupling of two very simple and highly accessible partners, highly conjugated acetylenes and transition metal carbene complexes, as the key elements for the design of new processes. New, efficient, and highly flexible synthetic route to a variety of target molecules utilizing these newly developed reactions have been proposed. Specific Aims 1-4 involve the tandem generation of isobenzofurans and/or pyrones and their subsequent cycloaddition reactions. Reliable protocols will be developed for the use of these reactions for the synthesis of ten-membered rings, partially hydrogenated phenanthrene ring systems, isoquinoline ring systems, and benzo-fused flve-membered ring heterocycles. These newly developed reaction processes will subsequently be used as cornerstones for incredibly short synthetic routes to the steroids, morphine alkaloids, hydrophenanthrene antibiotics, benzophenanthridine anti-cancer agents, and indole-containing phosphodiesterase inhibitors. The multicomponent nature of these couplings allows for a high degree of molecular diversity, a tremendous asset for long-term evaluation of structure-activity relationships of pharmaceutical analogs. Specific Aim 5 involves development of a novel synthetic route to the 1-aminopyrrole ring system based on the coupling of enyne-imines with carbene complexes. This reaction will serve as the cornerstone for the synthesis of unsymmetrical dipyrroles and a complementary method for the synthesis of partially hydrogenated phenanthrenes. This methodology will subsequently be employed in a short synthetic route to tanshinones, important components of then herb Dan Shen, and which display a diverse spectrum of biological activity. Specific Aim 6 involves extension of the above processes to the analogous epoxide or aziridine derivatives, and development of protocols for rapid assembly of the medicinally important 3-benzoxepine and 3-benzazepine ring systems.

本课题的研究重点是发展具有重要药用价值的杂环体系和碳环体系的制备方法。该方法利用两个非常简单和高度可接近的伙伴的耦合，高度共轭的乙炔和过渡金属碳配合物，作为设计新工艺的关键要素。利用这些新发展的反应，提出了一种新的、高效的、高度灵活的合成途径来合成各种目标分子。具体目的1-4涉及异苯并呋喃和/或吡喃的串联生成及其随后的环加成