Pericyclic Reactions for Organic Synthesis

有机合成的周环反应

• 批准号: 7392842
• 负责人: RICK L DANHEISER
• 金额: $ 29.91万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7392842
• 关键词: Alkaloids; Cardiovascular Diseases; Chemistry; Class; Cyclic Acetylenes; Development; Diels Alder reaction; Disease; FR 900482; Heterocyclic Compounds; Imines; Indoles; Investigation; Methodology; Methods; Nicotinic Receptors; Nitrogen; Organic Synthesis; Oxidation-Reduction; Oxygen; PQQ Cofactor; Pharmaceutical Preparations; Pharmacologic Substance; Process; Protein Tyrosine Kinase; Pyrroles; Reaction; Research; Research Personnel; Route; System; Variant; antimicrobial drug; antitumor agent; ascochlorin; base; cancer therapy; chemical synthesis; cycloaddition; indole; marine natural product; novel; programs; pyridine; tool; xestoquinone

DESCRIPTION (provided by applicant): This proposal focuses on the application of pericyclic reactions in new methodology for the synthesis of several important classes of carbocyclic and heterocyclic organic compounds. Part I describes the development of new strategies for the efficient synthesis of several classes of carbocyclic and heterocyclic compounds. Intramolecular [4 + 2] cycloaddition reactions of conjugated enynes will be investigated and employed in new routes to aromatic, dihydroaromatic, and seven-membered ring containing compounds. Heterocyclic variants of this process will be developed leading to five- and six-membered nitrogen and oxygen heterocycles. The application of this chemistry to the synthesis of pentacyclic polyketide marine natural products with protein tyrosine kinase inhibitory activity, the antitumor agent clavepictine A, and to the synthesis of quinolizidine and indolizidine alkaloids that are noncompetitive blockers for nicotinic receptor-channels will also be examined. Part II of the proposal describes the development of a tandem strategy in which a new ynamide-based benzannulation reaction is employed in conjunction with various heterocyclization processes to provide efficient access to polycyclic benzo-fused heteroaromatic systems including indoles, dihydroquinolines, and benzazocines. Applications of this chemistry to the synthesis of the antitumor agents ascochlorin and FR900482, the redox cofactor PQQ (methoxatin), and the alkaloid herbindole C are described. The new methods developed in this program will provide researchers with powerful new tools for the efficient chemical synthesis of several classes of organic compounds known to possess activity as pharmaceuticals. This research will thus benefit the development of new antimicrobial agents as well as drugs for the treatment of cancer, cardiovascular disease, and other disorders.

描述（由申请人提供）：本提案的重点是在合成几种重要的碳环和杂环有机化合物的新方法中应用周环反应。第一部分介绍了几种高效合成碳环和杂环化合物的新策略的发展。共轭炔分子内[4 + 2]环加成反应将被研究并应用于生成芳香族、二氢芳香族和含七元环化合物的新途径。这一过程的杂环变体将被开发，导致五元和六元氮和氧杂环。该化学在合成具有蛋白酪氨酸激酶抑制活性的五环聚酮类海洋天然产物、抗肿瘤药物克拉匹汀A以及作为烟碱受体通道非竞争性阻滞剂的喹啉吡啶和吲哚吡啶生物碱方面的应用也将被研究。该提案的第二部分描述了一种串联策略的发展，其中一种新的基于酰胺的苯并环反应与各种杂环化工艺相结合，以提供有效的多环苯并融合的杂芳香系统，包括吲哚，二氢喹啉和苯并辛。介绍了该化学在抗肿瘤药物抗坏血氯和FR900482、氧化还原辅助因子PQQ（甲氧xatin）和生物碱herbindole C的合成中的应用。在这个项目中开发的新方法将为研究人员提供强大的新工具，以有效地化学合成几种已知具有药物活性的有机化合物。因此，这项研究将有利于开发新的抗菌剂以及治疗癌症、心血管疾病和其他疾病的药物。