CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

描述：(申请人摘要)这项研究的长期目标是 生物医学上高效合成对映体纯品 采用手性镝的卡宾方法合成重要化合物(II) 或铜(I)催化剂。卡宾方法提供了一系列途径 碳-碳键的形成从加成延伸到插入和叶立德 已用于构建木脂素的生成/重排， 高对映体中的2-脱氧内酯和多种内酯、内酰胺类化合物 超标(94%或更多ee)，具有特殊的非对映-、区域-和 化学选择性。我们设计并合成了四类 二氢呋喃(II)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点， 预计催化剂的能力将进一步扩大。手性铜 催化剂，主要基于手性双恶唑啉配体，也将是 已评估。提出了一种新的高选择性合成方法。 取代缩醛保护的2-脱氧核内酯和2-脱氧核内酯 衍生物及其通过C-H插入的氮杂糖类似物。这是一样的 转化反应将是二十二烯合成的核心，这表明 聚集抑制活性。金属辅助叶立德生成和 重排将指向不对称合成 多官能/多取代氨基酸以及具有 阿尔法位置上的羟基，如芦荟皂苷元和维克斯特罗 据报道，其生物学效应是耐人寻味的。内生叶立德 将对多肽和蛋白质进行研究，以确定选择性、局部或 很遥远。大环环丙烷化反应--一种新的、极其简便的方法 方法学，为卡斯宾和二萜类化合物提供了方便的入口 内酯Pinnatin A和Pinnatin B是癌细胞细胞毒素。串列 双重氮酯通过环丙烷化或插入反应得到 实现复杂合成的机会，具有严格的选择性 包括双重非对映选择(高达99.4%ee)。最后， 与重氮甲烷的不对称环丙烷化反应一直难以捉摸， 将使用手性铜(I)和迪(II)进行详细的研究 催化剂。

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.