CYCLIZATION REACTIONS CATALYZED BY TRANSITION METALS

过渡金属催化的环化反应

• 批准号: 2178517
• 负责人: EI-ICHI NEGISHI
• 金额: $ 23.51万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2178517
• 关键词: alkenes; biological products; catalyst; chemical synthesis; cyclization; organometallic compounds; palladium; stereochemistry

One of the general objectives of the proposed research is to develop a new, efficient, and selective synthetic methodology applicable to the synthesis of a wide variety of organic compounds of medicinal and biological interest. To this end, carbometallation reactions involving late transition metal complexes, especially palladium complexes, as catalysts will be investigated and developed. In addition to those involving alkyl, lll, benzyl, alkenyl, aryl and alkynyl derivatives of palladium and other transition metals, addition reactions of acylpalladium (acylpalladation) and related derivatives will be developed. Since the majority of compounds of medicinal and biologically interesting compounds are cyclic, most of the efforts will be directed to the development of cyclic carbopalladation, cyclic acylpalladation, and related cyclization reactions. One of the main specific goals of the proposed research is to develop a conceptually novel "zipper"-mode cascade cyclization methodology based on cyclic carbopalladation, acylpalladation, and related reactions, which are expected to significantly expand the synthetic options and simplify the retro-synthetic analysis for preparing a wide variety of polyfused compounds. The second general objective is to actually demonstrate efficient and selective syntheses of organic compounds of medicinal and biological interest. The overall merit of such research activities transcends mere procurement of compounds of medicinal and biological importance. Besides being of medicinal and biological interest, the natural products dealt with in the proposed research are to help define the direction of the methodologial investigations and provide an indispensable means of critically evaluating their values. Indeed, the target compounds in the proposed research are primarily chosen from these latter viewpoints. Specifically, they include: nagilatone F, illudin M, sterpurene, frullanolide, paniculide A, nanaomycin A, daunomycinone aglycone, patulin, freelngyne, and 9Z-retinoic acid. Although not discussed in full detail, cortisone, jervine, rubrolides, and nostoclides will be considered as guides to methodological developments and potential future agents. Some final products as well as intermediates obtained in both methodological and application studies will be submitted for medicinal screening.

拟议研究的总体目标之一是开发一种新的、 适用于合成的高效、选择性合成方法 多种药用和生物有机化合物 兴趣。 为此，涉及后期的碳金属化反应 过渡金属络合物，特别是钯络合物，作为催化剂 将进行研究和开发。 除了涉及烷基的那些之外， III、钯等的苄基、烯基、芳基和炔基衍生物 过渡金属，酰基钯的加成反应（酰基钯化） 并开发相关衍生品。 由于大多数化合物 的医学和生物学上有趣的化合物是环状的，大多数 将致力于开发循环碳钯化， 环状酰基钯化反应和相关的环化反应。 主要之一 拟议研究的具体目标是开发一种概念新颖的 基于循环的“拉链”模式级联环化方法 碳钯化、酰基钯化和相关反应，它们是 预计将显着扩大合成选项并简化 用于制备多种多聚融合物的逆合成分析 化合物。 第二个总体目标是实际证明 药用有机化合物的高效选择性合成 生物学兴趣。 此类研究活动的总体优点 超越了单纯采购医药和生物化合物 重要性。 除了具有医学和生物学意义外， 拟议研究中涉及的天然产品将有助于定义 方法学研究的方向并提供不可或缺的 批判性地评估他们的价值观的方法。 事实上，目标化合物 在拟议的研究中，主要是从后面的观点中选择的。 具体来说，它们包括：nagilatone F、illudin M、sterpurene、 frullanolide、panululide A、nanaomycin A、daunomycinone 苷元、展青霉素、 游离炔和9Z-视黄酸。 虽然没有详细讨论， 可的松、jervine、红布罗内酯类和念珠菌素类药物将被视为 方法发展和潜在未来药物的指南。 一些 最终产品以及在方法和方法上获得的中间体 将提交应用研究进行药物筛选。