ASYMMETRIC DIELS-ALDER REACTIONS OF VINYLOGOUS URETHANES

乙烯基聚氨酯的不对称狄尔斯-阿尔德反应

• 批准号: 2187046
• 负责人: RICHARD H SCHLESSINGER
• 金额: $ 22.59万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2187046
• 关键词: Diels Alder reaction; antineoplastic antibiotics; carbohydrate analog; diene; stereochemistry; urethan

The objective of this new proposal is to devise a number of total syntheses of complex carbocycles exploiting a novel methodology, that employs chiral dienes ultimately derived from tetronic acids and proline in Diels-Alder (D-A) type reactions. The D-A reaction has become an extension of vinylogous urethane lactone (VUL) enolate carbon-carbon bond formation reactions. As functionally opulent dienes, these systems offer several synthetic advantages relative to other cycloaddition reactions. A major benefit is the formation of a bicyclic ketal, which can function as a protecting group for subsequent synthetic manipulations. These incipient nonracemic cycloadducts permit facile control in the introduction of additional asymmetric centers to the rigid oxa-[2.2.1]- bicyclic heptyl system. The ease of synthesis and accessibility of inexpensive starting materials makes these dienes applicable to large scale asymmetric synthesis. We intend to demonstrate the versatility of these novel dienes within the context of several short enantioselective syntheses of biologically active compounds, while concomitantly studying the origins of their p facial selectivity and expanding their applicability. It is our intent to effect a brief and efficient construction of the antitumor and antimicrobial, esperamicin as the aglycone (24) and several biologically active and distinct pseudo-sugars (50, 34, 43) using this methodology.

这项新提案的目标是制定一系列总体方案 利用一种新颖的方法合成复杂的碳环， 采用最终源自特窗酸和脯氨酸的手性二烯 狄尔斯-阿尔德 (D-A) 型反应。 D-A反应已成为 插烯氨基甲酸酯内酯 (VUL) 烯醇化物碳-碳键的延伸 形成反应。 作为功​​能丰富的二烯，这些系统提供 相对于其他环加成反应有几个合成优点。 一个主要好处是形成双环缩酮，它可以发挥作用 作为后续合成操作的保护基。 这些 初期的非外消旋环加合物可以轻松控制 在刚性 oxa-[2.2.1]- 中引入额外的不对称中心 双环庚基系统。 合成的容易性和可获取性 廉价的原材料使这些二烯适用于大型 规模不对称合成。 我们打算展示的多功能性 这些新颖的二烯在几个短对映选择性的背景下 生物活性化合物的合成，同时研究 他们的p面部选择性的起源并扩大他们的 适用性。 我们的目的是实现一个简短而有效的 抗肿瘤和抗菌药物esperamicin的构建 糖苷配基 (24) 和几种具有生物活性且独特的假糖 (50,34,43) 使用这种方法。