Methodology for, and Synthesis of Biologically Active Pyrrolidinone Natural Products.

生物活性吡咯烷酮天然产物的方法学和合成。

• 批准号: EP/J004499/1
• 负责人: Jonathan Burton
• 金额: $ 45.98万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FJ004499%2F1
• 关键词: Methodology; Synthesis; Biologically; Active; Pyrrolidinone

Five-membered ring compounds with contain one nitrogen atom, are ubiquitous structural units present on thousands of natural products, in numerous brand-name drugs and agrochemicals, and are widely used to modify catalysts for a particular purpose. These nitrogen "heterocycles" are present in a family of highly complex natural products which exhibit antitumour and antibiotic activity. The search for new antibiotics is particularly important now we are in the "post-penicillin" era and our entering the era when even resistance to antibiotics such as vancomycin is regularly encountered. The search for new antibiotics with different modes of action is an important challenge facing academia and the pharmaceutical industry. The aim of our work is to develop new and efficient methods for the synthesis of nitrogen heterocycles which will have particular application to the synthesis of these antitumour antibiotics. A major part of the project will involve using the developed methodologies to synthesise one of the natural products and, importantly, to prepare simplified analogues. The simplified analogues will be tested for both antibiotic and antitumour activity. In the long term, this research may have an impact on the discovery of new antibiotics and antitumour agents. Moreover, the developed methodologies will have application in the synthesis of a whole range of other biologically important natural products and small molecules.

含有一个氮原子的五元环化合物是数千种天然产物、众多名牌药物和农用化学品中普遍存在的结构单元，并广泛用于修饰特定用途的催化剂。这些氮“杂环”存在于一系列高度复杂的天然产物中，具有抗肿瘤和抗生素活性。现在我们正处于“后青霉素”时代，并且我们正在进入一个甚至经常遇到对万古霉素等抗生素产生耐药性的时代，寻找新的抗生素显得尤为重要。寻找具有不同作用方式的新型抗生素是学术界和制药行业面临的重要挑战。我们工作的目的是开发新的有效的氮杂环合成方法，该方法将特别应用于这些抗肿瘤抗生素的合成。该项目的主要部分将涉及使用已开发的方法来合成一种天然产物，并且重要的是，制备简化的类似物。将测试简化类似物的抗生素和抗肿瘤活性。从长远来看，这项研究可能会对新抗生素和抗肿瘤药物的发现产生影响。此外，所开发的方法将应用于合成一系列其他生物学上重要的天然产物和小分子。

项目成果

Short, Tin-Free Synthesis of All Three Inthomycins.

• DOI: 10.1002/chem.201803794
• 发表时间: 2018-11-13
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Kumar M;Bromhead L;Anderson Z;Overy A;Burton JW
• 通讯作者: Burton JW

Diastereoselective synthesis of fused lactone-pyrrolidinones; application to a formal synthesis of (-)-salinosporamide A.

稠合内酯-吡咯烷酮的非对映选择性合成；

• DOI: 10.1021/ol501662t
• 发表时间: 2014
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Logan AW