NIH-Administrative Support Supplement for Randolf Escobar.

NIH - 兰道夫·埃斯科瓦尔 (Randolf Escobar) 的行政支持补充。

• 批准号: 9309439
• 负责人: Scott Edward Schaus
• 金额: $ 0.55万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9309439
• 关键词: Acetals; Acids; Address; Aldehydes; Area; Biological; Boron; Boronic Acids; Breathing; Carbon; Carboxylic Acids; Catalysis; Chemicals; Chemistry; Collection; Coupling; Cyanides; Development; Diels Alder reaction; Drug Compounding; Glycols; Goals; Health; Isomerism; Ligands; Methodology; Methods; Modality; Natural Products; Organic Synthesis; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Phenols; Physical condensation; Process; Property; Reaction; Reagent; Research; Seminal; United States National Institutes of Health; bioactive natural products; carbanion; carbon compound; catalyst; design; enantiomer; human disease; hydronium ion; improved; innovation; insight; interest; novel; organic acid; prevent; programs; public health relevance; quinone methide

DESCRIPTION (provided by applicant): The development of new chemical methodologies is an important objective of organic synthesis. An area that continues to inspire chemists is the chemistry of organoboranes and boronates. The unique properties of boron and the ability to activate organic boronates to deliver carbon nucleophiles has yielded an impressive array of chemical methods and processes. We will extend the ability of organoboranes and boronates to deliver carbanion equivalents in novel condensation reactions including chemoselective carbonyl condensations and multicomponent reactions. The reactions will be rendered asymmetric through the development of asymmetric catalysts and chiral boronate reagents and the utility of the methods developed demonstrated by the asymmetric synthesis of pharmaceuticals and natural products. Significant advances have been made in the mechanistic understanding of boronate activation via ligand exchange with chiral diols. We will use the mechanistic insight we have obtained to expand the repertoire of reactions catalyzed by dynamic ligand exchange processes to include acyl cyanides as electrophiles, borono-Petasis reactions, and ortho-quinone methide chemistry. Our continued interest in reaction discovery has led to the identification of chiral diol acid catalysts capable of promoting the enantioselectie addition reactions to acetals. We seek to explore this reactivity and expand it to include types of functionalized nucleophiles in additions to oxoniums and iminiums and boronate hetero-Diels-Alder reactions. Goals of the research program include developing a breadth of reactivity, providing access to novel chiral blocks, and new reaction development. Bond constructions are selected to access chiral synthetic intermediates that could be used in the construction of pharmaceuticals and natural products. The results will transform the way boronate nucleophiles are utilized in enantioselective synthesis.

描述（由申请人提供）：发展新的化学方法是有机合成的一个重要目标。有机硼烷和硼酸盐的化学性质一直激励着化学家。硼的独特性质和激活有机硼酸盐以传递亲核碳试剂的能力已经产生了一系列令人印象深刻的化学方法和工艺。我们将扩展有机硼烷和硼酸盐在新型缩合反应中提供碳当量的能力，包括化学选择性羰基缩合和多组分反应。通过不对称催化剂和手性硼酸盐试剂的开发，以及通过药物和天然产物的不对称合成所证明的开发方法的实用，反应将呈现不对称。手性二醇与配体交换硼酸盐活化的机理研究取得了重大进展。我们将利用我们已经获得的机制洞察力来扩展由动态配体交换过程催化的反应库，包括酰基氰化物作为亲电试剂，硼- petasis反应和邻醌类化学。我们对反应发现的持续兴趣导致了能够促进缩醛对映选择性加成反应的手性二醇酸催化剂的鉴定。我们试图探索这种反应性，并将其扩展到包括类型