Diels-Alder/Ene Reactions for the Multi-Component Synthesis of Natural Product Inspired Bioactive Chemical Libraries

用于天然产物启发的生物活性化学库的多组分合成的 Diels-Alder/Ene 反应

• 批准号: EP/I033959/1
• 负责人: Michael Hall
• 金额: $ 12.6万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI033959%2F1
• 关键词: Diels; Alder; Ene; Reactions; Multi

Despite the many fantastic advances in health treatment over the past 50 years new drug molecules are always needed. Sometimes this is to combat existing health problems for which a solution is yet to be found, such as some cancers, and sometimes this is to deal with emerging problems, such as the rise of drug resistant bacteria (e.g. MRSA). Modern drug discovery relies on chemists to make new molecules for testing as potential drugs which can be then optimised to for use by a patient. However current approaches to this problem can be very time consuming and inefficient. The inefficiency of these processes also results in the creation of large quantities of chemical waste which can in turn cause environmental problems. This project aims to find a solution to this through the use of one-pot chemical reactions where, in place of sequential chemical transformations (one after the other), several can happen in the same reaction flask. This efficient approach leads to a vast reduction in the waste generated, whilst at the same time increases the number of different molecules a chemist can make in a day and thus the number of molecules which can be tested. Making many molecules, rapidly and with a reduction in waste can only help to speed up the drug discovery process.Specifically this project will develop new one-pot methods to make a library of very different molecules, very quickly. The molecules we will target have the potential to be new anticancer or new antibacterial agents, so will also test these molecules as lead compounds for treatment of these diseases.

尽管在过去的50年里，健康治疗取得了许多令人惊叹的进步，但人们总是需要新的药物分子。有时这是为了应对尚未找到解决方案的现有健康问题，如一些癌症，有时是为了应对新出现的问题，如耐药细菌(如耐甲氧西林金黄色葡萄球菌)的崛起。现代药物发现依赖于化学家制造用于测试的新分子，作为潜在的药物，然后可以优化以供患者使用。然而，目前解决这一问题的方法可能非常耗时且效率低下。这些过程的低效还导致产生大量化学废物，这反过来又会造成环境问题。该项目旨在通过使用一锅化学反应来找到解决方案，在这种反应中，可以在同一反应瓶中发生几次连续的化学反应，而不是顺序的化学反应(一个接一个)。这种有效的方法大大减少了产生的废物，同时增加了化学家一天可以制造的不同分子的数量，从而增加了可以测试的分子的数量。快速和减少浪费地制造许多分子只会有助于加快药物发现过程。具体地说，这个项目将开发新的一刀切方法，非常快地建立一个非常不同的分子库。我们将针对的分子有可能成为新的抗癌或新的抗菌剂，因此也将测试这些分子作为治疗这些疾病的先导化合物。

项目成果

Diastereoselective synthesis of functionalised carbazoles via a sequential Diels-Alder/ene reaction strategy

通过连续 Diels-Alder/ene 反应策略非对映选择性合成官能化咔唑

• DOI: 10.1039/c5ra00499c
• 发表时间: 2015
• 期刊: RSC Advances
• 影响因子: 3.9
• 作者: Cowell J

Diastereoselective rearomative etherifications and aminations of 2,3,9,9a-tetrahydro-1H-carbazoles

• DOI: 10.1016/j.tet.2021.132144
• 发表时间: 2021-04
• 期刊: Tetrahedron
• 影响因子: 2.1
• 作者: Matokah M. Abualnaja;Joseph Cowell;John D. Jolliffe;Corinne Wills;P. Waddell;W. Clegg;Michael J. Hall

Synthesis of pentacyclic pyrrolo[3,4-a]carbazole-1,3(2H)-diones via an intermolecular Diels-Alder, intramolecular carbonyl-ene reaction strategy

• DOI: 10.1016/j.tet.2016.08.008
• 发表时间: 2016-09
• 期刊: Tetrahedron
• 影响因子: 2.1
• 作者: Matokah M. Abualnaja;P. Waddell;W. Clegg;Michael J. Hall