Living vicariously - Merging biocatalysis and chemocatalysis for pyridine synthesis

该项目将利用生物催化和化学催化相结合的方法，利用综合催化的思想--同时使用化学和生物催化转化--来开发药物结构中最重要的基序之一--吡啶的新合成，以实现以前不可能实现的新的合成途径。串联工艺是原子效率的标志，可以大大减少化学工艺的环境足迹--这是未来可持续合成的公理。这一集成的方法将由两种催化模式的互补性驱动-TM催化的过程，如C-H活化和光氧化还原化学提供了一种利用未活化的底物形成C-C键的新方法，而生物催化在立体可控官能团操纵方面带来了巨大的力量。它们共同提供了一种构建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：我们如何为酶和有机合成系统创造相互兼容的反应条件，因为要求往往非常不同(特别是温度和溶剂)？这一问题的解决将对工业/制造化学具有深远的意义，使合成路线能够显著简化和加速。如果我们能够定义被证明协同工作的生物/化学催化剂对，我们就可以提供一种模块化的方法来合成有价值的基序(例如手性仲醇/胺、亚砜、所有烷基立体中心等)。以前所未有的速度和多功能性组装在一起。

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.