Living vicariously - Merging biocatalysis and chemocatalysis for pyridine synthesis

该项目将开发新的吡啶合成方法，吡啶是药物结构中最重要的基序之一，使用生物催化与化学催化相结合，使用综合催化的思想-同时使用化学和生物催化转化来实现以前不可能实现的新合成途径。串联过程是原子效率的标志，可以大大减少化学过程的环境足迹-未来可持续合成的公理。综合方法将由两种催化模式的互补性驱动- tm催化过程（如C-H活化和光氧化还原化学）为使用非活化底物形成C-C键提供了新的方法，生物催化在立体控制官能团操纵方面带来了巨大的力量。总之，它们提供了一种建立分子复杂性的新方法，同时简化了过程复杂性和成本。该项目将解决以下主要挑战：考虑到通常截然不同的要求（特别是温度和溶剂），我们如何为酶和有机合成系统创造相互兼容的反应条件？这个问题的解决方案将对工业/制造化学具有深远的意义，使合成路线大大简化和加速。如果我们能够定义一对被证明协同工作的生物/化学催化剂，我们就可以提供一种模块化的合成方法，从而以前所未有的速度和多功能性组装有价值的基序（例如手性仲醇/胺，亚砜，所有烷基立体中心等）。

This project will develop new syntheses of pyridines, one of the most important motifs in drug structures, using biocatalysis merged with chemocatalysis, using the idea of integrated catalysis - the concurrent use of chemo- and bio-catalytic transformations to enable novel synthetic pathways that were not previously possible. Tandem processes are a hallmark of atom-efficiency and can substantially reduce the environmental footprint of chemical processes - an axiom of sustainable synthesis for the future. The integrated approach will be driven by the complementarity of the two modes of catalysis - TM-catalysed processes such as C-H activation and photoredox chemistry offer a new approach to C-C bond formation using unactivated substrates, and biocatalysis brings tremendous power in terms of stereo-controlled functional group manipulation. Together, they offer a new way of building up molecular complexity whilst simplifying process complexity and cost. The project will address the following major challenge: How can we create mutually compatible reaction conditions for both enzymes and organic synthesis systems, given the often vastly different requirements (notably of temperature and solvent)? A solution to this problem would have far-reaching significance to industrial/manufacturing chemistry, enabling synthetic routes to be dramatically streamlined and accelerated. If we can define pairs of bio/chemo catalysts that are proven to work in synergy, we can provide a modular approach to synthesis whereby valuable motifs (e.g. chiral secondary alcohols/amines, sulfoxides, all alkyl stereocentres etc.) are assembled with unprecedented speed and versatility.