SYNTHETIC APPLICATIONS OF CONJUGATED KETENE DITHIOACETAL

共轭烯酮二硫缩醛的合成应用

• 批准号: 3291373
• 负责人: R Karl KARL DIETER
• 金额: $ 6.36万
• 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 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3291373
• 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.

本次调查的具体目的是探索和发展 α-氧代烯酮二硫代缩醛化学。 目前正在进行两项程序 开发的有效利用这一功能组， 选择性（即化学选择性、区域选择性和立体选择性） 碳-碳键结构和官能团操作。 的 第一种方法涉及化学选择性和立体选择性缀合物 将有机铜酸酯加成到α-氧代烯酮二硫代缩醛和 得到的乙烯基硫酯。 第二种方法涉及 对酮羰基进行1，2-亲核加成，然后进行酸加成 催化重排，并构成一个通用的1，3-羰基 允许区域选择性顺序的转座方法 碳-碳键结构 具体目标有两个方面。 第一、 这两种方法的范围、限制和反应参数 将被仔细研究 二、综合应用 这种化学方法应用于α-烷叉酮的合成， α-吡喃酮，简单的和环状的苯衍生物将是 考察 这些方法的发展将提供一般路线 几类化合物，并将提供多功能性， 构建特定的替代模式。 每个所述合成 应用将需要研究以优化反应条件， 确定合成路线的范围和限制。 的 开发方法，用于顺序区域，立体， 化学选择性地构建新的碳-碳键， α-氧代烯酮二硫缩醛级联将提供多功能合成 机会 在前期工作中，这些合成方法的力量 已经通过全合成Myodesmone来说明。 直接输入 区域和立体特异性取代的 烯丙醇是另一个例子。 杂环化合物（如： α-吡喃酮）和苯型芳族化合物将有助于 寻找活性药物化合物。 这些方法适用于 生物活性天然产物和合成物的合成 药物