Total Synthesis/Chloropeptin l/Anti-HIV Natural Product

全合成/氯肽素l/抗HIV天然产物

基本信息

批准号：
6931102
负责人：
JEROMY J COTTELL
金额：
$ 4.4万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-16 至 2006-07-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6931102
关键词：
HIV envelope protein gp120 HIV infections antiAIDS agent biological products chemical structure function chemical synthesis drug design /synthesis /production enzyme inhibitors human immunodeficiency virus inhibitor /antagonist integrase oligopeptides postdoctoral investigator protein binding stereoisomer

项目摘要

DESCRIPTION (provided by applicant): Chloropeptin I is a representative member of a class of macrocyclic peptides that show potent anti-HIV activity. Specifically, chloropeptin I shows micromolar inhibition of both gp120 binding and of HIV-integrase. Both of these actions represent underdeveloped areas in current HIV therapy, and therefore chloropeptin I warrants further investigation for possible drug development. This proposal outlines the enantioselective synthesis of chloropeptin I to unambiguously prove its structure and configuration. The approach will focus on the construction of the two macrocycles via macrolactamization, followed by radical cyclization, and by intramolecular nucleophilic aromatic substitution. Upon the completion of an efficient and scalable synthesis, chloropeptin analogs can be prepared with minimal alteration of the synthetic route. Access to these derivative will allow investigation of the structure activity relationship of chloropeptin I, in an effort to develop more effective inhibitors.

描述（由申请人提供）：氯肽I I是表现出有效抗HIV活性的一类大环肽的代表性成员。具体而言，氯肽I I显示了对GP120结合和HIV - 积极酶的微摩尔抑制作用。这两种动作都代表了当前艾滋病毒疗法中发育不足的地区，因此氯肽I值得进一步研究可能的药物开发。该建议概述了氯肽I I的对映选择性合成，以明确证明其结构和构型。该方法将通过大分子化将重点放在两个大环的结构上，然后进行自由基环化和分子内亲核芳族取代。完成有效且可扩展的合成后，可以通过最小的合成途径改变氯肽类似物。获取这些衍生物将允许研究氯肽I I的结构活性关系，以开发更有效的抑制剂。