NOVEL ORGANOMETALLIC ROUTES TO POLYENES & DERIVATIVES

拟议工作的广泛、长期目标是提供短期、 几种含多烯天然产物的快速构建方法 产品。三种不相关类型的多烯关系是 地址：(1)所有E，共轭聚烯烃；(2)跳过的Z-多烯；以及 (3)双跳多戊烯聚烯烃。具体地说，前者 分类会影响多烯大环内酯类化合物的全合成。这些 大环天然产物被广泛用作临床用药 系统性感染的治疗。跳过的聚烯，具有潜力 在信息素和从花生四烯酸衍生的分子等方面的应用 酸级联(如过敏反应的慢反应物质，SRSA的)， 后者在与呼吸道疾病的联系中尤为突出。 病痛。辅酶QN，它们组成了一组普遍存在的氧化还原 与线粒体呼吸链密切相关的成分有 也用于临床。这些有效方法的核心是 双分子在于新发现的进一步发展 有机金属方法学及其应用前景 通过适当设计的插销实现多烯结构。拿走 对称性元素或反应性分布差异的优势 在新型针脚的末端之间，通过试剂进行1锅缝合 用合适的亲电剂预制的“原位”是提供关键部件 目标分子的数量。这一新化学的进一步扩展到 还直接制备了高手性C-4-取代(双脱氧)核糖 想象中的。

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.