Asymmetric Umpolung Aldehyde Reactions

不对称醛醛反应

• 批准号: 8068335
• 负责人: Tomislav Rovis
• 金额: $ 27.34万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-05 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8068335
• 关键词: Aldehydes; Amides; Antifungal Agents; Biological; Biology; Catalysis; Chemistry; Complex; Development; Family; Goals; Health; Methodology; Methods; Oxidation-Reduction; Reaction; Reagent; Research; Route; Science; Structure; Techniques; Therapeutic Agents; Time; carbene; catalyst; cost; functional group; innovation; interest; member; novel; programs; public health relevance; small molecule

DESCRIPTION (provided by applicant): Project Summary The development of novel routes to stereochemically and structurally complex targets of biological interest remains of paramount importance. New strategies, bond disconnections, and catalysts that exploit standard functional groups in innovative ways each contribute to the overall goal of increased scope and efficiency, and decreased time and cost. Catalysis, the use of substoichiometric amounts of reagent, without the need for covalent attachment or pretreatment, carries with it the promise of greener, more efficient, more selective methods for synthesis. This proposal seeks to develop novel methods to use traditional functional groups in non-traditional ways, accessing hitherto unavailable bond disconnection strategies in an effort to greatly expand our toolkit. In the context of this research, we will apply these breakthroughs in order to prepare stermocurtisine and cephalomysin, two members of a family of biologically active agents whose activity spans from anti-fungal to anti-angiogenic and antitumor. We have further developed techniques for the selective and green synthesis of new amide bonds, ubiquitous functional groups in chemistry and biology. The specific goals of this research are as follows: 1) develop the catalytic enantioselective intermolecular Stetter reaction; 2) explore cascade catalysis using simple precursors to generate densely functionalized products; 3) pursue the rapid total synthesis of a variety of biologically important molecules using this approach; 4) investigate the redox chemistry of 1-reducible aldehydes using nucleophilic carbenes. The long-term impact of this science is to enable chemists to rapidly assemble complex structures with high efficiency. PUBLIC HEALTH RELEVANCE: Project Narrative One of the most significant barriers to health-related research involving small molecules is the rapid assembly of therapeutic agents. This proposal seeks to develop new methods to synthesize complex frameworks using easily accessible precursors with high efficiency.

描述（由申请人提供）：项目摘要开发新的路线，立体化学和结构复杂的生物学目标仍然是至关重要的。新的策略、键断和以创新方式利用标准官能团的催化剂都有助于实现增加范围和效率以及减少时间和成本的总体目标。催化，使用亚化学计量的试剂，而不需要共价连接或预处理，带来了更绿色，更有效，更选择性的合成方法的希望。该提案旨在开发新的方法，以非传统的方式使用传统的官能团，访问迄今为止不可用的键断开策略，努力大大扩展我们的工具包。在这项研究的背景下，我们将应用这些突破，以制备stermocurtisine和头孢菌素，一个家庭的两个成员的生物活性剂，其活性范围从抗真菌到抗血管生成和抗肿瘤。我们进一步开发了选择性和绿色合成新酰胺键的技术，这些酰胺键是化学和生物学中普遍存在的官能团。本研究的具体目标如下：1）发展催化的对映选择性分子间Stetter反应; 2）探索使用简单前体的级联催化以产生密集功能化产物; 3）追求使用该方法快速全合成多种生物重要分子; 4）研究使用亲核卡宾的1-可还原醛的氧化还原化学。这门科学的长期影响是使化学家能够快速高效地组装复杂的结构。 公共卫生相关性：涉及小分子的健康相关研究的最大障碍之一是治疗剂的快速组装。该提案寻求开发新的方法，以使用容易获得的前体高效率地合成复杂的框架。