Pyridine Synthesis via an Olefin C-H Alkenylation/Azaelectrocyclization Strategy

通过烯烃 C-H 烯基化/氮杂电环化策略合成吡啶

• 批准号: 7492338
• 负责人: Ashley Berman
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-16 至 2010-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7492338
• 关键词: Alkenes; Area; Biological; Biological Factors; Class; Development; Drug Compounding; Laboratories; Literature; Metals; Methodology; Methods; Nitrogen; Object Attachment; Pharmaceutical Preparations; Preparation; Prevalence; Research; Research Proposals; Swainsonine; System; Therapeutic; Variant; catalyst; pyridine; sugar

DESCRIPTION (provided by applicant): The development of methodology for the concise stereoselective synthesis of nitrogen-containing heterocycles is an active area of research, owing to the prevalence of such structural motifs in natural products and bioactive compounds. The pyridine motif (and saturated variants thereof) is in particular widely represented in compounds of biological importance, and consequently methods for its stereoselective preparation are well represented in the literature. It is the specific aim of this research proposal to outline a new method for the stereoselective preparation of such heterocycles employing a metal catalyzed olefinic C- H bond alkenylation/azaelectrocyclization sequence. This strategy allows for the concise stereoselective synthesis of pyridines, providing rapid access to this important class of compounds from readily available starting materials. Polysubstituted pyridines, chiral saturated pyridines, and uniquely fused bicyclic pyridine systems are all readily accessible using this new strategy. The application of this methodology to the total synthesis of the bioactive aza sugar (-)-swainsonine is also outlined. The development of new methods to concisely prepare therapeutic drugs in the laboratory continues to be an active area of research. This research aims to develop such new methods, and to apply them toward the preparation of drugs of potential therapeutic value.

描述（由申请人提供）：由于含氮杂环化合物的结构基序在天然产物和生物活性化合物中普遍存在，因此，含氮杂环化合物的简明立体选择性合成方法的开发是一个活跃的研究领域。吡啶基序（及其饱和变体）特别广泛地存在于具有生物学重要性的化合物中，因此其立体选择性制备方法在文献中有很好的描述。这是本研究建议的具体目标，概述了一种新的方法，采用金属催化的烯属C-H键烯基化/氮杂电环化序列的立体选择性制备这样的杂环。该策略允许吡啶的简明立体选择性合成，提供从容易获得的起始材料快速获得这类重要化合物。多取代吡啶，手性饱和吡啶，独特的稠合双环吡啶系统都很容易使用这种新的策略。本文还概述了该方法在生物活性氮杂糖（-）-苦马豆素全合成中的应用。在实验室中开发新的方法来简洁地制备治疗药物仍然是一个活跃的研究领域。本研究旨在开发这种新方法，并将其应用于制备具有潜在治疗价值的药物。