New Cyclization Methods and Multicomponent Couplings

超出所提供的空间。该提案的主要目标是开发用于合成复杂分子的强大方法。在本项目期间具体处理的新方法将依赖于镍金属环的催化生成和功能化。一种新的合成策略，采用连续的镍催化反应将开发，应提供访问各种碳环和杂环芳香族亚结构。其他新的环化方法，利用丙二烯前体和乙烯基锆前体将被开发。在合成方法学发展方面的努力应该为各种合成问题提供根本性的新解决方案。该计划的目标还包括利用该计划中开发的新反应全合成生物学上有趣的天然产物。将被追踪的靶分子包括龟鳖醇A和B、软骨藻酸、异软骨藻酸G和H、serratezomine A和pumiliotoxin 341 A。全合成中的这些问题将使我们能够寻求许多实质性合成挑战的解决方案，包括产生具有多个连续立构中心的密集官能化的五元和六元环，立体选择性地产生三取代和四取代的烯烃，以及立体选择性地产生季碳中心。此外，这些生物学上有趣的天然产物和密切相关的后期中间体的制备量的合成将允许评估它们作为潜在的药剂和作为药理学研究工具的效用。性能现场=

EXCEEDTHE SPACEPROVIDED. The primary objective of this proposal is to develop powerful methods for the synthesis of complex molecules. The new methods to be specifically addressed during this project period will rely on the catalytic generation and functionalization of nickel metallacycles. A new synthetic strategy employing sequential nickel-catalyzed reactions will be developed that should provide access to a variety of carbocyclic and heterocyclic aromatic substructures. Other new cyclization methods that utilize allene precursors and vinylzirconium precursors will be developed. The efforts in synthetic methodology development should provide fundamentallynew solutions to a variety of synthetic problems. \ The aims of this proposal also include the total syntheses of biologically interesting natural products utilizing new reactions developed in this program. The target molecules that will be pursued include testudinariols A and B, domoic acid, isodomoic acids G and H, serratezomine A, and pumiliotoxin 341A. These problems in total synthesis will allow us to pursue solutions to numerous substantial synthetic challenges including the generation of densely functionalized five and six membered rings that possess multiple contiguous stereocenters, the stereoselective generation of tri- and tetrasubstituted alkenes, and the stereoselective creation of quaternary carbon centers. Furthermore, the synthesis of preparative quantitiesof these biologically interesting natural products and closely related late stage intermediates will allow evaluation of their utility as potential pharmaceutical agents and as research tools in pharmacology. PERFORMANCE SITE ========================================Section End===========================================