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: 8006702
• 负责人: Kimberly Michelle Steward
• 金额: $ 2.91万
• 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 2014-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8006702
• 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; 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-酮酯在有机合成中发挥着重要作用，并且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，并且非常需要产生该功能的直接方法。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，以便将该子结构直接掺入亲电试剂中。所提出的化学方法将利用乙醛酸甲硅烷基酯，这是约翰逊实验室开发的一种独特的多功能联合试剂，在氰化物催化的醛加成中作为方便的亲核乙醛酸供体。还提出了用乙酰乙酸酯和p-亲电子试剂开发新型催化不对称加成/氧化反应级联。该反应将允许方便地获得对映体富集的α-酮酯。 公共健康相关性：对映体纯的生物相关小分子的合成是健康科学的一个重要领域，因为这些化合物用于探测生物过程中的结构-活性关系，并有可能作为新的化疗药物。希望尽可能有效地制备这些化合物，本次资助的目的是开发不对称反应以掺入α-酮酯部分。手性α-酮酯因其作为天然产物合成中间体的重要性及其在代谢和生物合成途径中的作用而受到特别关注。