ORGANOMETALLIC CYCLIZATION REACTIONS

有机金属环化反应

• 批准号: 3291241
• 负责人: EI-ICHI NEGISHI
• 金额: $ 20.33万
• 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 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3291241
• 关键词: alkenes; drug design /synthesis /production; isomer; organometallic compounds; prostacyclins; stereochemistry

The main objectives of the proposed research are twofold. The first is to develop fundamentally new cyclization methodologies based on the P.I.'s recent explorations of organotransition metal chemistry. Several intramolecular carbometallation reactions discovered and/or developed over the past several years form a basis for this part of the proposed research. Even now, there are a number of highly desirable chemical transformations that are difficult to achieve by conventional methods. Some such transformations include (i) efficient and selective synthesis of stereodefined exocyclic olefins, and (ii) cyclization, especially asymmetric cyclization, by generation of a quaternary carbon center including stereoselective synthesis of spirocycles. Also highly desirable is construction of bicycles and polycycles via multiple (three or more) carbon-carbon bond formation. It is intended to develop those methodologies which will provide attractive solutions to some of these synthetic problems. Specifically, various types of (i) cyclic acylpalladation, (ii) cyclic carbopalladation, especially multiple ring formation via carbopalladation, (iii) zirconium-promoted bicyclization of enzymes, and (iv) carbometallation of cyclopropenes, especially its asymmetric version, and its application to the synthesis of hydrazulenes will be investigated. The second objective of the proposed study is to apply new methodologies to the selective synthesis of natural or unnatural organic molecules of biological and medicinal interest. This will firstly provide very critical and stringent tests of the newly developed methodologies with regard to their potential synthetic utility. Secondly, some such synthetic endeavors will lead to the development of highly efficient routes to organic molecules of biological and medicinal importance. To these ends, the syntheses of select organic compounds including an antiblood clotting agent, carbacyclin (A-1), frullanolide (A- 2), and antibiotic, nanaomycin A(A-3), daunomycinone (A-4), and antiulcer agent, U-68,215(A-5), and beta-bulnesene (A-6) are planned. Some products as well as intermediates obtained in both exploration and application studies will be submitted to a few organizations for medicinal screening.

拟议研究的主要目标是双重的。 第一个是 基于 P.I. 开发全新的环化方法 有机过渡金属化学的最新探索。 一些 发现和/或开发的分子内碳金属化反应 过去几年的经验构成了这部分拟议研究的基础。 即使现在，仍有许多非常理想的化学转化 这是传统方法难以实现的。 一些这样的 转化包括（i）有效和选择性合成 立体定义的环外烯烃，和(ii)环化，特别是 通过生成季碳中心进行不对称环化 包括螺环的立体选择性合成。 也非常令人向往 是通过多个（三个或更多）制造自行车和多轮车 碳-碳键的形成。 其目的是开发那些 将为其中一些问题提供有吸引力的解决方案的方法论 综合问题。 具体来说，各种类型的（i）循环 酰基钯化，(ii)环状碳钯化，尤其是多环 通过碳钯化形成，(iii) 锆促进的双环化 酶，以及（iv）环丙烯的碳金属化，特别是其 不对称形式及其在腙烯合成中的应用 将被调查。 拟议研究的第二个目标是 将新方法应用于天然或非天然的选择性合成 具有生物和医学意义的有机分子。 这首先会 对新开发的产品进行非常关键和严格的测试 关于其潜在合成效用的方法论。 第二， 一些这样的综合努力将导致高度的发展 获得生物和医药有机分子的有效途径 重要性。 为此，选择有机化合物的合成 包括抗凝血剂、碳环素 (A-1)、呋喃内酯 (A- 2)、抗生素、纳霉素A(A-3)、道诺霉素(A-4)、抗溃疡药 计划使用 U-68,215(A-5) 和 β-布黎烯 (A-6)。 部分产品 以及在探索和应用中得到的中间体 研究将提交给一些组织进行医学筛选。