Novel Direct Approaches Toward Bioactive Heterocycles

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型有效环化方法。拟议项目包括两个主要部分。第一部分是关于重要的杂环系统的建设的新方法的发展。在整个第一部分，我们讨论了进一步的发展，最近发现的，新的铜辅助环异构化反应的炔基亚胺成吡咯。显着的注意力将支付给级联和顺序协议的发展，提供快速和方便的访问缩合含吡咯杂环和喹啉。该项目的第二部分是针对快速构建具有生物重要性的杂环分子的新合成方法的开发。为了进行这些合成，我们将依赖于使用上述环化方案。首先，我们将研究非对映选择性的方法对各种类型的吲哚里西啶生物碱。然后，我们将探讨使用这些方法对映选择性地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，重点将放在发现和采用控制环化步骤的选择性和效率所需的因素上。在完成模型研究后，将开展重要生物靶标的合成。开发高效的新型杂环化方法将扩大我们对杂环化学的了解，并为组装健康相关科学中感兴趣的杂环靶标提供强有力的方法。

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.