Pericyclic Reactions for Organic Synthesis

描述（由申请人提供）：该提案侧重于周环反应在合成几类重要的碳环和杂环有机化合物的新方法中的应用。第一部分介绍了几类碳环和杂环化合物的有效合成的新策略的发展。共轭烯炔的分子内[4 + 2]环加成反应将被研究和应用于芳香族、二氢芳香族和含七元环化合物的新路线中。将开发该方法的杂环变体，从而产生五元和六元氮和氧杂环。这种化学的应用与蛋白酪氨酸激酶抑制活性的五环聚酮海洋天然产物的合成，抗肿瘤剂clavepictine A，并合成的quinolizidine和indolizidine生物碱，烟碱受体通道的非竞争性阻滞剂也将进行检查。该提案的第二部分描述了一种串联策略的发展，其中采用了一种新的基于苯并环化的反应与各种杂环化过程相结合，以提供有效的多环苯并稠合杂芳族系统，包括吲哚，二氢喹啉和苯并氮杂环辛。本文介绍了这种化学方法在合成抗肿瘤剂子囊二氢卟酚和FR 900482、氧化还原辅因子PQQ（甲氧沙丁）和生物碱herbindole C中的应用。该计划开发的新方法将为研究人员提供强大的新工具，用于高效化学合成已知具有药物活性的几类有机化合物。因此，这项研究将有利于开发新的抗微生物剂以及治疗癌症，心血管疾病和其他疾病的药物。

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.