NATURALLY OCCURRING POLYENES VIA ORGANOMETALLICS

通过有机金属学天然存在的多烯

• 批准号: 2022232
• 负责人: BRUCE H. LIPSHUTZ
• 金额: $ 18.35万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2022232
• 关键词: antifungal agents; chemical conjugate; chemical synthesis; copper; eicosanoids; nickel; organometallic compounds; palladium; polyenes; stereochemistry; tin; ubiquinone; zinc; zirconium

During the past two years we have initiated a program in polyene chemistry, which has been directly supported by NIH grant GM 40287. The accent associated with the work described is on the development of new methodology, based in large measure on vinylic organometallics, since coupling reactions of sp2 carbon centers bearing a metal tend to retain their stereochemical integrity. A number of polyene types were identified, including (1) conjugated, all E polyenes, containing between four and seven olefins, typified by the polyene macrolides. These natural products are potent, clinically useful antifungals; (2) doubly skipped polyenes, characteristic of the ubiquinones (CoQn). These coenzymes are valuable in vivo antioxidants. A third type of polyene, distinct from those above, is the biaryl nucleus. With each of these specific functional groups, novel reagents and/or technologies were envisioned which rely on either cuprate mediated transmetalations between vinylic stannanes or zirconocenes, or 'kinetic' higher order cuprate oxidations toward unsymmetrical biaryls. Lastly, new methodology for rapid construction of the prostanoid skeleton has been developed, the scope of which is to be examined. As an outgrowth of these projects, the discoveries made have expanded our involvement in organometallics to include (beyond Cu, Sn, and Zr) organozinc, palladium and nickel chemistry as they relate to polyenes as well. Thus, this renewal application will highlight our accomplishments relating to GM 40287, point out the important discoveries made along the way, and then focus attention, in large measure, on the new directions planned which rely on a variety of organometallic intermediates.

在过去的两年里，我们在多烯方面发起了一个项目 化学，它已经得到了美国国立卫生研究院赠款GM 40287的直接支持。这个 与所述工作相关的重点是关于开发新的 方法学，在很大程度上基于乙烯有机金属学，因为 含金属的sp2碳中心的偶联反应倾向于保留 他们的立体化学完整性。鉴定了许多多烯类型， 包括(1)共轭的，所有E多烯，含有四和 七种烯烃，以多烯大环内酯为代表。这些天然产品 是有效的、临床上有用的抗真菌药物；(2)双跳多烯， 辅酶Q(CoQn)的特性。这些辅酶在 体内抗氧化剂。与上述类型不同的第三种类型的多烯是 联芳基核。对于这些特定的官能团中的每一个，都是新颖的 设想了依赖于任何一种铜酸盐的试剂和/或技术 乙烯基锡烷或锆烯之间的转金属反应，或 “动力学”高级铜酸盐氧化成不对称的联芳基。 最后，提出了一种快速构建前列腺素骨架的新方法 已经制定，其范围有待审查。作为一个副产品 在这些项目中，所取得的发现扩大了我们对 有机金属包括(除铜、锡和锆外)有机锌、钯 以及镍化学，因为它们也与多烯有关。 因此，此续订申请将突出我们在以下方面的成就 向GM 40287指出一路上的重要发现，以及 然后，在很大程度上，将注意力集中在计划的新方向上 它依赖于各种有机金属中间体。