Asymmetric Umpolung Aldehyde Reactions

不对称醛醛反应

• 批准号: 8851917
• 负责人: Tomislav Rovis
• 金额: $ 9.19万
• 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 2014-09-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8851917
• 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; 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.

开发具有生物学意义的立体化学和结构复杂靶点的新途径仍然是至关重要的。新策略、键断开和催化剂以创新的方式利用标准官能团，每一个都有助于扩大范围和效率，减少时间和成本。催化，使用亚化学计量量的试剂，不需要共价连接或预处理，带来了更环保，更有效，更有选择性的合成方法的希望。该提案旨在开发以非传统方式使用传统官能团的新方法，访问迄今为止不可用的键断开策略，以努力极大地扩展我们的工具包。在本研究的背景下，我们将利用这些突破来制备stermocurtisine和cephalomysin，这两个生物活性药物家族的成员，其活性从抗真菌到抗血管生成和抗肿瘤。我们进一步开发了新的酰胺键、化学和生物学中普遍存在的官能团的选择性和绿色合成技术。本研究的具体目标如下：1)开发催化对映选择性分子间Stetter反应；2)探索利用简单前体进行级联催化生成密集功能化产物；3)利用这种方法追求多种生物重要分子的快速全合成；4)利用亲核碳烯研究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。