SYNTHETIC APPLICATIONS OF CONJUGATED KETENE DITHIOACETAL

共轭烯酮二硫缩醛的合成应用

• 批准号: 3291372
• 负责人: R Karl KARL DIETER
• 金额: $ 6.28万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1988-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3291372
• 关键词: allyl compound; carbonyl compound; cyclic alcohol; cyclic compound; dithiol; drug design /synthesis /production; heterocyclic compounds; ketal; ketene

The specific aim of this investigation is to explore and develop the chemistry of Alpha-oxoketene dithioacetals. Two procedures are being developed for the efficient exploitation of this functional group for selective (i.e. chemoselective, regioselective and stereoselective) carbon-carbon bond constructions and functional group manipulations. The first method involves the chemoselective and stereoselective conjugate addition of organocuprates to Alpha-oxoketene dithioacetals and to the resultant vinylogous thioesters. The second method involves 1,2-nucleophilic additions to the ketone carbonyl followed by acid catalyzed rearrangement and constitutes a versatile 1,3-carbonyl transposition methodology that permits regioselective sequential carbon-carbon bond constructions. The specific goals are two-fold. First, the scope, limitations, and reaction parameters of these two procedures will be examined in very careful detail. Second, the synthetic application of this chemistry to the synthesis of Alpha-alkylidene ketones, Alpha-pyrones, and simple and annulated benzene derivatives will be examined. Development of these methodologies will provide general routes to several classes of compounds and will provide versatility for the construction of specific substitution patterns. Each of the synthetic applications will require studies to optimize reaction conditions and determine the scope and limitations of the synthetic routes. The development of methods for the sequential regio-, stereo-, and chemoselective construction of new carbon-carbon bonds utilizing the Alpha-oxoketene dithioacetal cascade will provide versatile synthetic opportunities. In preliminary work the power of these synethetic methods has been illustrated by a total synthesis of Myodesmone. The direct entry into the rich chemistry of regio- and stereospecifically substituted allylic alcohols provides another example. The development of methods for the synthesis of heterocycles (e.g. Alpha-pyrones) and benzenoid aromatic compounds will contribute to the search for active medicinal compounds. The methodologies are applicable to the synthesis of biologically active natural products and synthetic medicinals.

这项调查的具体目的是探索和开发 α-氧化烯二乙烯的化学。 两个程序正在 为有效利用该功能组而开发的 选择性（即化学选择性，区域性和立体选择性） 碳碳键结构和功能组操作。 这 第一种方法涉及化学选择性和立体选择性共轭物 向α-氧化烯二硫代乙烯的添加有机酸盐，并向 由此产生的乙烯基硫代植物。 第二种方法涉及 1,2核粉添加到酮羰基，然后是酸 催化重排和构成多功能1,3-键盘 允许区域选择顺序的转座方法 碳碳键结构。 具体目标是两个方面。 第一的， 这两个过程的范围，局限性和反应参数 将非常详细地检查。 第二，合成应用 这种化学的合成α-烷基酮酮的化学 Alpha-Pyrones，简单而环状的苯衍生物将是 检查。 这些方法的开发将提供一般路线 到几类化合物，将为该化合物提供多功能性 特定替代模式的构建。 每个合成 应用将需要研究以优化反应条件和 确定合成路线的范围和局限性。 这 开发顺序区域，立体声和 利用新碳碳键的化学选择性结构 α-oxoketene dithioEcetal Cascade将提供多功能合成 机会。 在初步工作中 已经通过肌无力的总合成来说明。 直接进入 进入富含区域和立体特定化学的化学反应 烯丙基醇提供了另一个例子。 杂环合成方法的发展（例如 Alpha-Pyrones）和苯甲酸芳香化合物将有助于 搜索活跃的药用化合物。 该方法适用于 生物活性天然产物和合成的合成 药用。