Accessing pharmacophoric space via asymmetric protonation

通过不对称质子化进入药效空间

• 批准号: EP/S027165/1
• 负责人: Allan Watson
• 金额: $ 50.96万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS027165%2F1
• 关键词: Accessing; pharmacophoric; space; via; asymmetric

Asymmetric catalysis has revolutionized the way molecules are made and are essential to the continued production of myriad products from small bioactive molecules to materials and from small scale to manufacture. A number of these processes have become privileged, with their impact demonstrated from tonne-scale application to the Nobel Prize. Increased mechanistic understanding of catalytic reactions underpins improvements of existing processes while driving development of new methods. By interrogating reactivity and selectivity in a newly described reaction, this proposal aims to bring new understanding to the underpinning catalytic processes while providing methods for the preparation of novel and synthetically powerful architectures.Our preliminary studies using asymmetric protonation have recently been published and provide a solid foundation for the proposed work. A series of additional supporting proof-of-concept experiments in support of this proposal have also given strong confidence in being able to deliver upon the objectives and aims of this proposal.This proposal will comprehensively investigate this asymmetric protonation platform to allow predictability and the rational application of this chemistry as a method for the generation of scaffolds tailored towards application in Medicinal Chemistry, with specific applications within Chemical Development in collaboration with our industrial project partner.

不对称催化已经彻底改变了分子的制造方式，并且对于从小生物活性分子到材料以及从小规模到制造的无数产品的持续生产至关重要。其中一些工艺已成为特权，其影响力从吨级应用到诺贝尔奖都得到了证明。对催化反应机理的进一步理解支持了现有工艺的改进，同时推动了新方法的开发。通过在一个新描述的反应中询问反应性和选择性，该提议旨在为基础催化过程带来新的理解，同时为制备新颖和合成功能强大的架构提供方法。我们最近发表了使用不对称质子化的初步研究，为拟议的工作提供了坚实的基础。一系列额外的支持性概念验证实验也为实现本提案的目标和目的提供了强大的信心。本提案将全面研究这种不对称质子化平台，以允许可预测性和合理应用这种化学作为生成药物化学应用的支架的方法，与我们的工业项目合作伙伴合作，在化学开发中提供特定的应用。

项目成果

Asymmetric Synthesis of Heterocyclic Chloroamines and Aziridines by Enantioselective Protonation of Catalytically Generated Enamines.

• DOI: 10.1002/chem.202200060
• 发表时间: 2022-03-16
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)

Asymmetric synthesis of heterocyclic chloroamines and aziridines by enantioselective protonation of catalytically generated enamines

通过催化生成烯胺的对映选择性质子化不对称合成杂环氯胺和氮丙啶

• DOI: 10.33774/chemrxiv-2021-d41h5
• 发表时间: 2021
• 作者: McLean L

An Alternative Synthesis of Cycloalkyl-Substituted CPA Catalysts and Application in Asymmetric Protonation Reactions**

• DOI: 10.1002/ejoc.202100980
• 发表时间: 2021-09
• 期刊: European Journal of Organic Chemistry
• 影响因子: 2.8
• 作者: Liam A. McLean;A. Watson