Automated stopped-flow library synthesis for rapid optimisation and machine learning directed experimentation.

ABSTRACT: For the discovery of new candidate molecules in the pharmaceutical industry, library synthesis is a critical step, in which library size, diversity, and time to synthesise are fundamental. In this work we propose stopped-flow synthesis as an intermediate alternative to traditional batch and flow chemistry approaches, suited for small molecule pharmaceutical discovery. This method exploits the advantages of both techniques enabling automated experimentation with access to high pressures and temperatures; flexibility of reaction times, with minimal use of reagents (μmol scale per reaction). In this study, we integrate a stopped-flow reactor into a high-throughput continuous platform designed for the synthesis of combinatory libraries with at-line reaction analysis. This approach allowed ∼900

SUBMITTER: Avila C 

PROVIDER: S-EPMC9601405 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature