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(申请人提供)：A-酮酯在有机合成中起着重要作用，是许多生物活性天然产物的普遍亚结构。α-酮酯结构的引入是一种综合的挑战，并且非常需要用于产生这种官能团的直接方法。这项建议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，以允许该亚结构直接结合到亲电体中。拟议的化学将利用乙氧基硅酸盐，这是约翰逊实验室开发的一种独特的多功能结合剂，在氰化物催化的醛加成反应中作为亲核乙醛供体。开发了一种新型的乙酰乙酸酯和亲电体级联催化不对称加成/氧化反应。该反应可方便地获得富含对映体的α-酮酯。 与公共健康相关：对映体生物相关小分子的合成是健康科学中的一个重要领域，因为这些化合物被用来探索生物过程中的结构-活性关系，并可能作为新的化疗药物。人们希望尽可能高效地制备这些化合物，这笔赠款的目的是开发不对称反应来结合a-酮酯部分。手性α-酮酯因其在天然产物合成中的重要作用以及在代谢和生物合成途径中的作用而备受关注。