NOVEL ORGANOMETALLIC ROUTES TO POLYENES & DERIVATIVES

合成多烯的新有机金属路线

• 批准号: 3297688
• 负责人: BRUCE H. LIPSHUTZ
• 金额: $ 15.87万
• 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 1993-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3297688
• 关键词: alkenes; carbopolycyclic compound; chemical synthesis; conformation; copper; leukotrienes; macrolide antibiotics; organometallic compounds; pheromone; polyenes; ribose; saturated /unsaturated bonds; stereochemistry; tin; ubiquinone

The broad, long term objectives of the proposed work are to provide short, rapid approaches to the construction of several polyene-containing natural products. Three unrelated types of polyene relationships are to be addressed: (1) all E, conjugated polyolefins; (2) skipped Z-polyenes; and (3) doubly skipped, polyprenoidal polyolefins. Specifically, the former classification will impact on polyene macrolide total synthesis. These large ring natural products are widely used as clinical agents for treatment of systemic infection. Skipped polyenes, with potential applications to e.g., pheromones and molecules derived from the arachidonic acid cascade (such as the slow reacting substances of anaphylaxis, SRSA's), the latter being especially prominent in their association with respiratory ailments. Coenzymes Qn, which make up a group of ubiquitous redox components intimately involved in the mitochondrial respiratory chain, are used clinically as well. The heart of the approach to these potent bimolecules lies in the further development of newly discovered organometallic methodology, with applications envisioned for effecting polyene construction via appropriately designed lynchpins. Taking advantage of either symmetry elements or differences in reactivity profiles between the termini of the novel lynchpins, 1-pot stitching via reagents preformed 'in-situ' with suitable electrophiles is to afford key components of the target molecules. Further extension of this new chemistry to the direct preparation of homochiral C-4-substituted (dideoxy) riboses is also envisioned.

拟议工作的广泛，长期目标是提供简短的， 快速构建几种含聚乙烯的天然的方法 产品。 三种无关类型的多烯关系将是 地址：（1）所有E，共轭聚烯； （2）跳过Z-Polyenes；和 （3）双重跳过的多点聚烯烃。 具体来说，前者 分类将影响多烯大花环总合成。 这些 大环天然产品被广泛用作临床药物 治疗全身感染。 跳过多烯，潜力 源自蛛网膜的信息素和分子的应用 酸级联（例如过敏反应的缓慢反应物质，SRSA）， 后者在与呼吸系统的关联中特别突出 疾病。 辅酶QN，构成一组无处不在的氧化还原 密切参与线粒体呼吸链的组件是 在临床上也使用。 这些有力的方法的核心 双莫勒分子在于新发现的进一步发展 有机金属方法论，设想应用的应用 通过适当设计的Lynchpins的多烯结构。 服用 对称元素的优点或反应性曲线的差异 在新颖林奇宾的末端，通过试剂缝制1锅 预先形成的“原位”，具有合适的电力，是提供关键组件 目标分子的。 将这种新化学反应进一步扩展到 直接制备异尿C-4溶解（dideoxy）核糖也是 设想。