Accessing pharmacophoric space via asymmetric protonation

不对称催化使分子的制造方式发生了革命性的变化，对于从小的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。许多这样的过程已经成为特权，它们的影响从吨级应用到诺贝尔奖上得到了体现。对催化反应的机理了解的增加为现有工艺的改进奠定了基础，同时推动了新方法的开发。通过对一种新描述的反应的反应性和选择性的考察，这一建议旨在为支撑催化过程带来新的理解，同时为制备新的和合成功能强大的结构提供方法。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。支持这一提议的一系列额外的支持性概念验证实验也给了人们对能够实现这一提议的目的和目的的强烈信心。这项提议将全面调查这个不对称质子化平台，以允许预测和合理应用这种化学作为一种方法来生成针对药物化学应用而量身定做的支架，并与我们的工业项目合作伙伴合作在化学开发中进行具体应用。

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.