CAREER: Development and Applications of Catalytically Generated Activated Carboxylates

职业：催化生成的活化羧酸盐的开发和应用

• 批准号: 0449587
• 负责人: Jeffrey Bode
• 金额: $ 57.5万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0449587&HistoricalAwards=false
• 关键词: CAREER; Development; Applications; Catalytically; Generated

Intramolecular redox reactions of a-functionalized aldehydes mediated by N-heterocyclic carbenes (or heterocyclic ylides) lead to the catalytic generation of activated carboxylates, suitable for the synthesis of esters, amides, and other carboxylic acid derivatives under economical and environmentally friendly reaction conditions. The discovery of this novel reactivity, mediated by an organic catalyst, of a-heteroatomic and a,b-unsaturated aldehydes opens a broad range of mechanistically unique pathways for the synthesis of chiral carboxylic acid derivatives, including anti-b-hydroxyesters and b-amino peptides. The design and application of chiral heterocyclic salts for catalyzing this novel process will provide an enantioselective method for directly controlling the absolute stereochemistry concomitant with esterifications and peptide couplings, and has the potential to supplant traditional multi-step chiral auxiliary based methodologies. By developing means of effecting the direct, enantioselective synthesis of amides from a,b-didehydroamino aldehydes, a waste-free, atom-economical approach to the synthesis of poly-a-amino-peptides from achiral precursors will emerge. The unique reactivities of unsaturated aldehydes under these catalytic conditions will enable novel carbon-carbon bond forming processes, including new annulation reactions affording lactones, lactams, and cyclopentanones, thereby providing a long-sought method for the direct, intermolecular synthesis of hetero- and carbocycles from stable, readily available starting materials. Applications of these new reactions include the synthesis of (1) short, biologically active a- and b-peptides, (2) the kalafungin class of naturally occurring antibiotics, and (3) the antibiotic moiramide B, which is active against drug resistant bacterial strains.With the support of this CAREER award from the Organic and Macromolecular Chemistry Program, Professor Jeffrey W. Bode, of the Department of Chemistry and Biochemistry at the University of California, Santa Barbara, is developing new reactions catalyzed by simple organic molecules rather than by metals. This reaction chemistry not only offers promise of great chemical selectivity, but also represents an economical, environmentally friendly ("green") approach to organic synthesis, eliminating the use of potentially hazardous metals and greatly reducing waste generation. Professor Bode will exploit the newly discovered reaction chemistry for the synthesis of a variety of products, including biologically active polypeptides and antibiotics, demonstrating the potentially broad applicability of this chemistry in the synthesis of important products. He will also engage undergraduate students, both at UCSB and from local community colleges, in an alternative sophomore level organic laboratory course aimed at exposing them to hands-on training in the realities of inquiry and research based organic chemistry.

n -杂环羰基（或杂环酰基）介导的a-官能化醛分子内氧化还原反应可催化生成活性羧酸盐，适用于在经济环保的反应条件下合成酯类、酰胺类及其他羧酸衍生物。这种由有机催化剂介导的a-杂原子和a，b-不饱和醛的新反应性的发现，为手性羧酸衍生物的合成开辟了广泛的机制独特的途径，包括抗b-羟基酯和b-氨基肽。手性杂环盐的设计和应用将为直接控制伴随酯化和肽偶联的绝对立体化学提供一种对映选择性方法，并有可能取代传统的多步手性辅助方法。通过开发直接、对映选择性地从a，b-二脱氢氨基醛合成酰胺的方法，将出现一种无浪费、原子经济的从非手性前体合成聚a-氨基肽的方法。在这些催化条件下，不饱和醛的独特反应活性将使新的碳-碳键形成过程成为可能，包括产生内酯、内酰胺和环戊酮的新的环化反应，从而为从稳定、现成的起始材料直接合成杂环和碳环提供了一种长期寻求的方法。这些新反应的应用包括(1)短的，具有生物活性的a-和B -肽的合成，(2)卡拉芬金类天然存在的抗生素，以及(3)对耐药菌株具有活性的抗生素莫伊酰胺B。在有机和大分子化学项目颁发的CAREER奖的支持下，加州大学圣巴巴拉分校化学和生物化学系的Jeffrey W. Bode教授正在开发由简单有机分子而不是金属催化的新反应。这种反应化学不仅提供了很大的化学选择性，而且代表了一种经济、环保（“绿色”）的有机合成方法，消除了潜在有害金属的使用，大大减少了废物的产生。Bode教授将利用新发现的反应化学来合成各种产品，包括生物活性多肽和抗生素，展示该化学在合成重要产品方面的潜在广泛适用性。他还将邀请加州大学圣迭戈分校和当地社区学院的本科生参加另一门大二水平的有机实验课程，目的是让他们在有机化学的探究和研究中获得实际的实践训练。