Catalytic Nucleophilic Glyoxylation: Asymmetric Derivatizations and Aldol/Oxidati

催化亲核乙醛酸化：不对称衍生化和羟醛/氧化

• 批准号: 8213128
• 负责人: Kimberly Michelle Steward
• 金额: $ 1.87万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-15 至 2012-07-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8213128
• 关键词: 3-hydroxybutanal; Acetoacetates; Aldehydes; Anions; Area; Biological Factors; Biological Process; Chemistry; Cyanides; Development; Felis catus; Generations; Glycols; Glyoxylates; Grant; Health Sciences; Kinetics; Laboratories; Metabolic; Methods; Organic Chemistry; Organic Synthesis; Pathway interactions; Play; Procedures; Reaction; Reagent; Resolution; Role; Scheme; Structure; Structure-Activity Relationship; adduct; base; catalyst; chemotherapeutic agent; glyoxylate; interest; novel; oxidation; public health relevance; small molecule

DESCRIPTION (provided by applicant): a-Ketoesters play an important role in organic synthesis and are prevalent substructures of many biologically active natural products. The introduction of the a-ketoester structure is synthetically challenging and direct methods for the generation of this functionality are highly desirable. This proposal aims to develop practical new catalytic reactions that provide the synthetic equivalents of glyoxylate anions to allow the direct incorporation of this substructure into electrophiles. The proposed chemistry will utilize silyl glyoxylates, a unique versatile conjunctive reagent developed in the Johnson laboratory, to serve as a convenient nucleophilic glyoxylate donor in cyanide catalyzed additions to aldehydes. The development of a novel catalytic asymmetric addition/oxidation reaction cascade with acetoacetates and p-electrophiles is also proposed. This reaction will allow expedient access to enantioenriched a-ketoesters. PUBLIC HEALTH RELEVANCE: The synthesis of enantiopure biologically-relevant small molecules is an important area in the health sciences, as these compounds are used to probe structure-activity relationships in biological processes and can potentially serve as new chemotherapeutic agents. It is desirable to prepare these compounds as efficiently as possible and this grant aims to develop asymmetric reactions to incorporate the a-ketoester moiety. Chiral a-ketoesters are of particular interest due to their importance as intermediates in natural product synthesis and their roles in metabolic and biosynthetic pathways.

描述（由申请人提供）：α-酮酯在有机合成中起重要作用，是许多生物活性天然产物的普遍亚结构。α-酮酯结构的引入在合成上具有挑战性，并且用于产生该官能团的直接方法是高度期望的。该提案旨在开发实用的新催化反应，提供乙醛酸阴离子的合成等价物，以允许将该子结构直接并入亲电体。拟议的化学将利用甲硅烷基乙醛酸酯，一个独特的多功能的连接试剂开发的约翰逊实验室，作为一个方便的亲核乙醛酸供体氰化物催化添加到醛。发展了一种新的催化不对称加成/氧化反应级联与乙酰乙酸酯和p-亲电试剂。该反应将允许方便地获得对映体富集的α-酮酯。 公共卫生关系：对映体纯的生物相关小分子的合成是健康科学中的一个重要领域，因为这些化合物用于探测生物过程中的结构-活性关系，并且可以潜在地用作新的化疗剂。希望尽可能有效地制备这些化合物，并且该授权旨在开发不对称反应以掺入α-酮酯部分。手性α-酮酯由于其作为天然产物合成中的中间体的重要性以及其在代谢和生物合成途径中的作用而受到特别关注。