제 목 : Organic Synthesis in Automated Flow Chemistry Platform
연 사 : 황예진 교수(인하대학교 화학공학과)
일 시 : 2019년 5월 10일(금) 오전 11시-12시
장 소 : 화학관 2층 세미나실 (330226호실)
Organic Synthesis in Automated Flow Chemistry Platform
Assistant Professor Department of Chemical Engineering, Inha University, Incheon
There is increasing pressure in drug discovery to deliver a steady stream of active compounds for physicochemical profiling and potency testing. In order to accelerate lead optimization, it is imperative to reduce the time required for each iteration of design, synthesis, and screening. I will present an automated chemistry platform that can efficiently screen a wide range of reactions, including single/multi-phase, single/multi-step, and photochemical reactions at the 14 microliter scale. Individual droplets are prepared by a liquid handler and moved through fluoropolymer tubing by a carrier gas at elevated pressures. Reactions occur in a heated reactor where the liquid droplet is oscillated back and forth to ensure thorough mixing – even for biphasic liquid-liquid reactions or liquid-gas reactions – without being limited to a finite residence time. Optional inlet and/or outlet injections enable multistep chemistry. A portion of the crude product mixture is sampled and sent directly to an online HPLC/MS for analysis, purification, and product collection, typically of 10-500 μg. The system offers the enhanced heat and mass transfer characteristics, increased safety, and opportunity for automation associated with flow chemistry while enabling the following key advantages: (a) reduction of material consumption, preparing just 40 microliters for each reaction condition, (b) elimination of residence time dispersion, (c) elimination of the inverse relationship between residence time and mass transfer rate for a flow reactor of fixed length, (d) simplification of continuous and discrete variable screening through the use of a liquid handler to prepare reaction mixtures, and (e) elimination of the time- and material-waste associated with waiting for flow reactors to reach steady state. Importantly, because the reaction droplet is equivalent to one segment in a continuous segmented flow, reaction conditions identified using the platform can be directly translated to a continuous synthesis. This helps bridge the connection between the early research stages of drug discovery and the later stages, where material demands grow from the μg-mg scale to the g-kg scale.