Chemistry of Lithium Enolates

烯醇锂的化学性质

• 批准号: 8069864
• 负责人: DAVID B. COLLUM
• 金额: $ 31.31万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069864
• 关键词: 3-hydroxybutanal; Acylation; Alkylation; Analytical Chemistry; Anti-Asthmatic Agents; Case Study; Chemistry; Collaborations; Colorectal Cancer; DNA Sequence Rearrangement; Drug Industry; Fostering; Funding; Group Processes; Investigation; Kinetics; Laboratories; Lithium; Methods; NMR Spectroscopy; Organic Chemistry; Organic Synthesis; Pharmacologic Substance; Physical condensation; Process; Protocols documentation; Reaction; Reagent; Solutions; Staging; Structure; abstracting; base; computational chemistry; design; improved; programs; public health relevance

DESCRIPTION (provided by applicant): Project Summary/Abstract Lithium enolates constitute one of he most important classes of reactive intermediate in organic synthesis. The pharmaceutical industry uses these reagents frequently and on very large scales. In this proposal we describe efforts to understand the underlying chemistry of the most important reactions of lithium enolates. With methods to establish solution structures that dominated the first funding period largely developed, structural studies will be more targeted in support of mechanistic studies. In the most general sense, we will examine how solvation and aggregation influence reactivity. The mechanistic investigations will focus on specific classes of reaction-case studies-that include: (1) aza-aldol condensations; (2) O-silylations; (3) alkylations; (4) acylations; (5) [2,3]- and [3,3]-sigmatropic rearrangements; and (6) nucleophilic aromatic substitutions (SNAr). A uniquely integrated approach based on a combination of NMR spectroscopy, solution kinetics, and computational chemistry will develop an understanding of the mechanistic principles and how to control reactivity and selectivity. By bringing synthetic organic, physical organic, analytical, and computational chemistry together under one roof, we reveal the consequences of solvation and aggregation with an unprecedented clarity. PUBLIC HEALTH RELEVANCE: Project Narrative Lithium enolates are reactive intermediates used by other academic and pharmaceutical process chemistry laboratories on a daily basis around the globe. Our mechanistic studies described herein are designed to understand and improve their efficacy. The project originated from collaboration with Sanofi-Aventis to develop anti-asthmatics. The proposed funding period includes a collaboration with Amgen as part of their program to synthesize treatments for colorectal cancer.

描述（由申请人提供）：项目摘要/摘要锂含有构成有机合成中最重要的反应性中间体之一。制药行业经常使用这些试剂在很大的尺度上。在这项建议中，我们描述了了解锂烯醇最重要反应的基本化学的努力。借助建立统治第一个融资时期的解决方案结构的方法，结构研究将更具针对性的机械研究。从最一般的意义上讲，我们将研究溶剂化和聚集如何影响反应性。机械研究将集中于特定类型的反应案例研究，其中包括：（1）AZA-ALDOL冷凝； （2）o-silylions; （3）烷基化； （4）酰化； （5）[2,3] - 和[3,3] - 含量重排； （6）亲核芳族取代（SNAR）。基于NMR光谱，溶液动力学和计算化学的组合的独特整合方法将发展对机械原理以及如何控制反应性和选择性的理解。通过在一个屋顶下将合成有机，物理有机，分析和计算化学反应融合在一起，我们以前所未有的清晰度揭示了溶剂化和聚集的后果。 公共卫生相关性：项目叙事锂烯醇是其他学术和药物过程化学实验室使用的反应性中间体，每天在全球范围内使用。我们所描述的机械研究旨在理解和提高其功效。该项目起源于与Sanofi-Aventis合作开发抗asthmatics。拟议的资金期限包括与Amgen的合作，作为其计划合成结直肠癌治疗的一部分。