Novel Direct Approaches Toward Bioactive Heterocycles

描述（由申请人提供）：计划开发新的和有效的环化方法来合成具有生物意义的杂环化合物。拟议的项目包括两个主要部分。第一部分讨论了构建重要杂环系统的新方法的发展。在整个第一部分中，我们讨论了最近发现的一种新的铜辅助炔基亚胺环异构化反应的进一步发展。将重点关注级联和顺序方案的发展，提供快速和方便的途径，以浓缩含吡咯的杂环和喹啉。该项目的第二部分旨在开发新的合成方法，以快速构建具有重要生物学意义的杂环分子。为了进行这些合成，我们将依赖于使用上述环化协议。首先，我们将研究不同类型的吲哚嘧啶生物碱的非对映选择方法。然后，我们将探索利用这些方法对映选择性构建吲哚吡啶和吡咯利西啶环体系的可行性。在发展新的合成方法时，重点将放在发现和采用控制环化步骤的选择性和效率所必需的因素。在完成模型研究后，将进行生物学重要靶点的合成。高效的新杂环化方法的发展将扩大我们对杂环化学的认识，并为我们在健康科学中组装感兴趣的杂环靶点提供有力的方法。

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.