IRON COMPLEXES IN ACYCLIC POLYENE SYNTHESIS

无环多烯合成中的铁络合物

• 批准号: 3301377
• 负责人: William A Donaldson
• 金额: $ 6.49万
• 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/3301377
• 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.

白三烯 (LT) 是脂质代谢物，可充当支气管和 血管收缩剂，已知可增加血管通透性。 研究结果表明，抑制剂在体内形成 白三烯在治疗以下疾病方面可能具有治疗价值 支气管哮喘和过敏反应。 由于天然含量低 LT 的丰富性，只有合成的可用性 白三烯和白三烯衍生物将允许未来 生物作用和代谢的机制研究 这些重要的生物分子。 白三烯结构提出了两个合成挑战—— 顺式二乙烯基甲烷官能团和立体定向 引入烯丙基氧官能团。 新合成 将制定方法来应对这两个挑战 利用 1) 简便的准备、分辨率和 手性（二烯）铁阳离子与亲核试剂的反应性 提供反式，顺式-1,3-二烯。 由于共轭三烯部分 已知白三烯结构的结构极其敏感 对于空气氧化，通过络合对多烯进行“保护” 铁将在准备和 处理这些敏感化合物。 多烯大环内酯类是一类不断增长的新型抗生素。 这些化合物的特点是具有共轭多烯链段 （4-7 个双带）以及包含多达 四个连续的手性中心。 新的合成方法将 为这些中心的不对称合成而开发 最初的前手性二烯。 这将通过以下方式完成 与立体化学定向铁（三羰基）络合 附件。