Integrated Biochemo-catalysis for Asymmetric Arylation

化学和生物催化的整合提供了一种可持续的方法来制造分子，从而实现无废物合成，催化或无金属替代现有试剂，以及在简化过程复杂性和成本的同时建立分子复杂性的新方法。从这个角度进行合成对未来的化学至关重要，因为所有相互关联的因素（试剂、溶剂、产率、中间体、催化剂等）都可以系统地优化，以获得最佳的合成路线。然而，挑战是巨大的——我们如何为酶和化学系统创造相互兼容的反应条件，考虑到通常截然不同的要求（特别是温度和溶剂）？化学催化和生物催化的结合代表了一个新兴的研究领域，它将成为未来化学和制造业的核心，对我们社会的福利和运作至关重要。这两种催化机制是高度互补的，化学催化提供了强大的C-C键策略，可以与酶控制的不对称官能团转化相结合——这是一种受生物合成理想启发的方法。不依赖贵金属催化的芳基化对当前化学思想具有挑战性和高度影响力，为从事该项目的iCAT学生创造了高影响力的出版物。该项目将提供生物催化、光氧化还原催化、有机催化、蛋白质表达和纯化、生物测定、不对称合成和水化学等领域的培训，以满足CDT的使命宣言，即培养能够在化学连续体中工作的下一代科学家，并为未来在不断变化、敏捷的行业中担任领导角色做好准备。该项目源于Greaney和Turner实验室在综合催化方面的长期合作，在生物氧化还原和C-H基化方面取得了进展，为iCAT学生实现雄心勃勃的研究目标提供了同事、设备和想法的支持框架。Turner和Greaney团队都与工业集团（如先正达，阿斯利康，葛兰素史克）广泛合作，围绕提案中提出的芳基化和生物催化转化概念，将最终用户互动带入项目，并帮助学生在其研究生涯的早期阶段创建一个科学网络。

The integration of chemo- and biocatalysis offers a sustainable approach to making molecules which enables waste-free synthesis, catalytic or metal-free alternatives to current reagents, and a new way of building up molecular complexity whilst simplifying process complexity and cost. Approaching synthesis from this perspective will be critical to future chemistry, where all inter-related factors (reagents, solvent, yields, intermediates, catalysts etc) can be systemically optimized for the best synthetic route. The challenges, however, are substantial - how can we create mutually compatible reaction conditions for both enzymes and chemo systems, given the often vastly different requirements (notably of temperature and solvent)?The integration of chemocatalysis and biocatalysis represents an emerging area of research that will be central to the future chemical and manufacturing industries, activities that are crucial to the welfare and operation of our society. The two regimes of catalysis are highly complementary, with chemocatalysis offering powerful C-C bond strategies that can be merged with asymmetric functional group transformations controlled by an enzyme - an approach that is inspired by the ideality of biosynthesis. Arylation without recourse to precious metal catalysis is challenging and highly influential to current thinking in chemistry, creating high impact publications for the iCAT student engaged on the project. The project will provide training in areas such as biocatalysis, photoredox catalysis, organocatalysis, protein expression and purification, biological assay, asymmetric synthesis, and aqueous chemistry, meeting the mission statement of the CDT to create the next generation of scientist who can operate across the chemical continuum and is equipped for future Leadership roles in a changing, agile industry. The project has grown from a long-standing collaboration between the Greaney and Turner laboratories in integrated catalysis that has produced advances in bio-redox and C-H arylation, providing a supportive framework of co-workers, equipment and ideas in which the iCAT student can realise the ambitious goals of the research. Both the Turner and Greaney groups collaborate extensively with industrial groups (e.g. Syngenta, AZ, GSK) around the arylation and biocatalysis transformation concepts set out in the proposal, bringing end-user interactions to the project and helping the student create a scientific network in the early stages of their research career.