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Pericyclic Reactions for Organic Synthesis

有机合成的周环反应

基本信息

批准号：
7778924
负责人：
RICK L DANHEISER
金额：
$ 29.3万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-07-01 至 2012-02-28
项目状态：
已结题

项目摘要

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(申请人提供)：本提案重点介绍周环反应在合成几类重要碳环和杂环有机化合物的新方法中的应用。第一部分描述了有效合成几类碳环和杂环化合物的新策略的发展。共轭烯炔的分子内[4+2]环加成反应将被用于合成芳香族、二氢芳香族和七元环化合物的新路线。这一过程的杂环变体将被开发，从而产生五元和六元氮和氧杂环。还将考察该化学在合成具有蛋白酪氨酸激酶抑制活性的五环多酮海洋天然产物抗肿瘤药物克拉维汀A，以及合成非竞争性烟碱受体通道阻滞剂喹诺利定和吲哚里西定生物碱方面的应用。该提案的第二部分描述了串联策略的开发，在该策略中，新的基于ynamide的苯环化反应与各种杂环化过程相结合，以提供有效的途径来获得多环苯并稠杂芳香族体系，包括吲哚、二氢喹啉和苯并唑。介绍了该化学在合成抗癌药物抗坏血酸和FR900482、氧化还原辅因子PQQ(甲氧菌素)和生物碱除草剂C中的应用。该计划中开发的新方法将为研究人员提供有效的新工具，用于几类已知具有药物活性的有机化合物的有效化学合成。因此，这项研究将有助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。