A Heterocycle Vending Machine: Towards the autonomous and self-optimising synthesis of a heterocyclic screening collection of fragments and lead-like

This project will develop an end-to-end heterocycle synthesis 'vending machine' that will enable the diversity-oriented synthesis of heterocycles in an autonomous and self-optimised fashion. By combining recent advances in light-activated
fundamental organic transformations, flow chemistry technology and self-optimisation algorithms, a telescoped multi-step process will be developed for the synthesis of novel heterocylic compounds. A variety of activated-methylene compounds and halo-alcohols/-amines with varied substitution patterns and chain length will be combined through the same sequence via formation and reaction of diazo compounds, and sequential cyclisation. It is envisioned that these simple commercially available building blocks will be fed into the machine, reacted in a self-optimised process to produce high value heterocyclic compounds with potential applications in the pharmaceutical sector. This approach, will deliver varied substituted heterocycles on demand, avoiding many repetitive steps by being directly applicable across different substrates. Compounds will be targeted to be appropriate as fragments or lead-like compounds for screening against biological targets. The integration of in-line optical detection in the flow process will facilitate the generation of real-time continuous data that will be fed into a self-optimising algroithim enabling reaction parameters (light, reaction time/flow rate, heat etc.) to be changed 'on the fly' in order to map out the optimum reaction conditions for a specific reaction.