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、长期目标是提供短期、 快速构建几种含多烯的天然 产品. 三种不相关的多烯关系将被 涉及：（1）所有E，共辄聚烯烃;（2）跳跃的Z-多烯;和 (3)双跳跃的聚异戊二烯类聚烯烃。 具体而言，前者 分类将影响多烯大环内酯的全合成。 这些 大环天然产物广泛用作临床药剂， 治疗全身性感染。 跳过的多烯，具有潜在的 应用于例如，来自花生四烯酸的信息素和分子 酸级联反应（如过敏反应的慢反应物质，SRSA）， 后者在与呼吸系统疾病的关系中尤其突出， 疾病 辅酶Qn，其构成一组普遍存在的氧化还原酶， 与线粒体呼吸链密切相关的组分， 临床上也有使用。 这些有效方法的核心 双分子在于进一步发展新发现的 有机金属方法，与应用设想的影响， 通过适当设计的关键点进行多烯结构。 以 对称元素或反应性分布差异的优点 在新型关键销的末端之间，通过试剂进行一锅缝合 用合适的亲电试剂“原位”预成型的方法是提供关键组分 的靶分子。 将这种新化学方法进一步扩展到 直接制备纯手性C-4-取代的（双脱氧）核糖， 预想的