IRON COMPLEXES IN ACYCLIC POLYENE SYNTHESIS

无环多烯合成中的铁络合物

• 批准号: 3301381
• 负责人: William A Donaldson
• 金额: $ 6.62万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3301381
• 关键词: Diels Alder reaction; alleles; antibiotics; asthma; diene; drug design /synthesis /production; hypersensitivity; iron; leukotrienes; metal complex; organometallic compounds; polyenes; stereochemistry; vascular endothelium permeability; vasoconstrictors

Leukotrienes (LT's) are lipid metabolites which act as broncho and vasoconstrictors and are known to increase vascular permeability. Findings indicate that inhibitors toward the in vivo formation of leukotrienes could be of therapeutic value in the treatment of bronchial asthma and allergic reactions. Due to the low natural abundance of the LT's, only the availability of synthetic leukotrienes and leukotriene derivatives will permit future mechanistic studies of the biological action and metabolism of these important bio-molecules. The leukotriene structure presents two synthetic challenges--the cis-divinylmethane functionality and the stereospecific introduction of allylic oxygen functionality. New synthetic methodology will be developed to address these two challenges by taking advantage of 1) the facile preparation, resolution, and reactivity of chiral (diene) iron cations with nucleophiles to afford trans,cis-1,3-dienes. Since the conjugated triene portion of the leukotriene structure is known to be extremely susceptible to air oxidation, the "protection" of the polyene by complexation to iron will be a tremendous advantage in the preparation and handling of these sensitive compounds. A growing new class of antibiotics are the polyene macrolides. These compounds are characterized by a conjugated polyene segment (4-7 double bands) as well as adjacent segments containing up to four contiguous chiral centers. New synthetic methodology will be developed for the asymmetric synthesis of these centers utilizing an originally prochiral diene. This will be accomplished through complexation to the stereochemically directing iron(tricarbonyl) adjunct.

白细胞（LT）是脂质代谢产物，充当支气管和 血管收缩剂，众所周知会增加血管通透性。 调查结果表明，对体内形成的抑制剂 白三烯在治疗中可能具有治疗价值 支气管哮喘和过敏反应。 由于自然低 LT的丰度，只有合成的可用性 白细胞和白三烯衍生物将允许未来 生物学作用和代谢的机械研究 这些重要的生物分子。 白三烯结构提出了两个综合挑战 - 顺式二甲基甲烷功能和立体特异性 引入烯丙基氧功能。 新的合成 将开发方法来解决这两个挑战 利用1）便利准备，解决方案和 手性（Diene）铁阳离与亲核的反应性 负担得起，cis-1,3-dienes。 自共轭三位生部分以来 已知白三烯结构非常敏感 为了空气氧化，通过络合物对多烯的“保护” 熨烫将是准备工作中的巨大优势 处理这些敏感化合物。 一类新的抗生素是多烯大环内酯类药物。 这些化合物的特征是共轭多烯段 （4-7个双频段）以及包含最高的相邻段 四个连续的手性中心。 新的合成方法将是 为这些中心的不对称合成而开发的 最初是核心狄恩。 这将通过 立体化学指导铁（Tricarbonyl）的络合 附件。