Novel Direct Approaches Toward Bioactive Heterocycles

生物活性杂环化合物的新颖直接方法

• 批准号: 6542393
• 负责人: VLADIMIR GEVORGYAN
• 金额: $ 23.24万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6542393
• 关键词: alkaloids; chemical synthesis; cyclization; heterocyclic compounds; imines; indolizines; pyrroles; stereochemistry

DESCRIPTION (provided by applicant): The development of novel and efficient cyclization methods for the synthesis of biologically significant heterocyclic compounds is planned. The proposed project consists of two major sections. The first section is concerned with the development of new methodologies for the construction of important heterocyclic ring systems. Throughout the first section, we discuss further developments of a recently discovered, novel copper-assisted cycloisomerization reaction of alkynyl imines into pyrroles. Significant attention will be paid to the development of cascade- and sequential protocols, providing rapid and convenient access to condensed pyrrole-containing heterocycles and quinolines. The second section of the project is directed toward development of new synthetic approaches for the expeditious construction of biologically important heterocyclic molecules. To carry out these syntheses, we will rely on using the above-mentioned cyclization protocols. Initially we will examine diastereoselective approaches toward various types of indolizidine alkaloids. We will then explore the feasibility of enantioselectively constructing indolizidine and pyrrolizidine ring systems using these methods. In developing new synthetic methods, an emphasis will be placed on discovering and employing factors necessary for controlling both the selectivity and efficiency of cyclization steps. After completing model studies, the synthesis of biologically important targets will be carried out.The development of highly efficient new heterocyclization methodologies will expand our knowledge of heterocyclic chemistry and provide us with powerful approaches for assembling heterocyclic targets of interest in the health-related sciences.

描述（由申请人提供）：计划开发用于合成具有生物学意义的杂环化合物的新颖且有效的环化方法。拟议项目由两个主要部分组成。第一部分涉及构建重要杂环系统的新方法的开发。在第一部分中，我们讨论了最近发现的新型铜辅助炔基亚胺环异构化反应成吡咯的进一步发展。将重点关注级联和顺序方案的开发，以提供快速、方便地获得稠合的含吡咯杂环和喹啉的方法。该项目的第二部分旨在开发新的合成方法，以快速构建生物学上重要的杂环分子。为了进行这些合成，我们将依赖于使用上述环化方案。首先，我们将研究各种类型的吲哚里西啶生物碱的非对映选择性方法。然后我们将探讨使用这些方法对映选择性构建吲哚里西啶和吡咯里西啶环系统的可行性。在开发新的合成方法时，重点将放在发现和利用控制环化步骤的选择性和效率所需的因素上。完成模型研究后，将进行生物学上重要靶标的合成。高效新杂环化方法的开发将扩展我们对杂环化学的知识，并为我们组装健康相关科学中感兴趣的杂环靶标提供强大的方法。