CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

用于对映选择性合成的手性催化剂

• 批准号: 6179371
• 负责人: Michael PATRICK Doyle
• 金额: $ 13.78万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6179371
• 关键词: carbene; catalyst; chemical synthesis; copper; cyclization; cyclopropanes; lactones; lignans; organometallic compounds; rhodium; stereochemistry; stereoisomer; ylide

DESCRIPTION: (Applicant's Abstract) The long-term objective of this research is the effective and efficient synthesis of enantiomerically pure, biomedically important compounds by carbene methodologies that employ chiral dirhodium(II) or copper(I) catalysts. Carbene methodologies offer a spectrum of pathways for carbon-carbon bond formation extending from addition to insertion and ylide generation/rearrangement that have been used for the construction of lignans, 2-deoxyxylolactone, and a variety of lactones and lactams in high enantiomeric excess (94 percent or more ee) with exceptional diastereo-, regio-, and chemoselectivity. We have designed and synthesized four classes of dirhodium(II) carboxamidates whose reactivities and selectivities offer unique advantages to asymmetric syntheses that involve metal carbene intermediates, and a further expansion in catalyst capabilities is anticipated. Chiral copper catalysts, mainly based on chiral bis-oxazoline ligands, will also be evaluated. New methods are proposed for the highly selective synthesis of acetal-protected 2-deoxyxylolactone and 2-deoxyribonolactone, substituted derivatives, and their aza-sugar analogs via C-H insertion. This same transformation will be the core for the synthesis of imperanene, which shows aggregation inhibitory activity. Metal-assisted ylide generation and rearrangement will be directed to the asymmetric synthesis of multifunctional/multisubstituted amino acids as well as to lignans having a hydroxyl group at the alpha position, such as trachelogenin and wikstromol whose biological effects are reported to be intriguing. Ylide generation within peptides and proteins will be investigated to determine selectivity, local or remote. Macrocyclic cyclopropanation, a new and exceptionally facile methodology, offers convenient entry to casbene as well as to the diterpenoid lactones pinnatin A and pinnatin B which are cancer cell cytotoxins. Tandem reactions of bis-diazoesters either via cyclopropanation or insertion affords the opportunity to achieve complex syntheses with exacting selectivity that includes double diastereoselection (up to 99.4 percent ee). Finally, enantioselective cyclopropanation with diazo-methane, which has been elusive, will be examined in critical detail using chiral copper(I) and dirhodium(II) catalysts.

描述：（申请人的摘要）这项研究的长期目标是 对映体纯的有效和有效合成，生物治疗 使用手性dirhodium（II）的Carbene方法论的重要化合物（II） 或铜（i）催化剂。 Carbene方法论提供了一系列途径 碳碳键形成从添加到插入和ylide延伸 用于建造木兰的发电/重排 高对照组中的2-脱氧氧基甲酮，以及多种内酯和乳糖 超过（94％或更多EE）具有特殊的iatereo-，regio-和recio-和 化学选择性。我们设计并合成了四类 Dirhodium（ii）羧酰胺的反应性和选择性提供了独特的 涉及金属卡宾中间体的不对称合成的优势， 预计催化剂能力会进一步扩展。手性铜 催化剂，主要基于手性bis-恶唑啉配体，也将是 评估。为高度选择性合成而提出了新方法 受乙酰保护的2-脱氧氧基甲酮和2-脱氧核糖核酸酮，取代 衍生物及其通过C-H插入的Aza-Sugar类似物。也是如此 转化将是繁殖繁殖的核心，这表明 聚集抑制活性。金属辅助Ylide世代和 重排将针对不对称合成 多功能/多取代的氨基酸以及具有 在α位的羟基，例如Trachelin和Wikstromol 据报道，其生物学作用引人入胜。内部的产生 将研究肽和蛋白质，以确定选择性，局部或 偏僻的。大环环甘油植物，一种新的和异常的 方法论，可方便地进入卡斯宾以及二萜 癌细胞细胞毒素的内舌蛋白A和Pinnatin B的内酯。串联 双二氮杂志的反应是通过环丙烷化或插入的反应 以精确的选择性获得复杂合成的机会 包括双映射（最高为99.4％的EE）。最后， 用重氮 - 甲烷的对映选择性环丙烷化，这是难以捉摸的 将使用手性铜（I）和Dirhodium（II）对临界细节进行临界检查 催化剂。