CHIRAL CATALYSTS FOR ENANTIOSELECTIVE SYNTHESES

描述：（申请人摘要）本研究的长期目标是 对映体纯的生物医学上有效和高效的合成 通过使用手性二铑（II）的卡宾方法制备的重要化合物 或铜（I）催化剂。卡宾方法提供了一系列的途径， 碳-碳键的形成从加成延伸到插入和叶立德 已经用于构建木酚素的生成/重排， 2-脱氧木糖内酯，以及各种高对映异构体的内酯和内酰胺 过量（94%或更高ee），具有异常的非对映体、区域和 化学选择性我们设计并合成了四类 二铑（II）羧酰胺化物，其反应性和选择性提供独特的 涉及金属卡宾中间体的不对称合成的优点， 并且预期催化剂能力的进一步扩展。手性铜 主要基于手性双恶唑啉配体的催化剂也将被 评估。本文提出了高选择性合成三羟甲基丙烷的新方法。 取代的缩醛保护的2-脱氧木糖内酯和2-脱氧核糖内酯 衍生物和它们的氮杂糖类似物通过C-H插入。同样的 转化将是合成欧前胡烯的核心， 聚集抑制活性。金属辅助叶立德生成和 重排将被导向不对称合成 本发明涉及多功能/多取代的氨基酸以及具有多功能/多取代的氨基酸的木脂素。 α位的羟基，如络石苷元和wikstromol 据报道其生物学效应非常有趣。内叶立德生成 肽和蛋白质将被研究，以确定选择性，局部或 遥控器大环环丙烷化，一种新的和非常容易的 方法学，提供了方便的进入，以casbene以及二萜类化合物 内酯pinnatin A和pinnatin B，它们是癌细胞毒素。串联 通过环丙烷化或插入使双重氮酯反应， 实现具有严格选择性的复杂合成的机会， 包括双重非对映选择（高达99.4%ee）。最后， 重氮甲烷的对映选择性环丙烷化，这一直是难以捉摸的， 将使用手性铜（I）和二铑（II）进行详细的研究 催化剂的

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.