Bayesian Optimization of Computer-Proposed Multistep Synthetic Routes on an Automated Robotic Flow Platform.

ABSTRACT: Computer-aided synthesis planning (CASP) tools can propose retrosynthetic pathways and forward reaction conditions for the synthesis of organic compounds, but the limited availability of context-specific data currently necessitates experimental development to fully specify process details. We plan and optimize a CASP-proposed and human-refined multistep synthesis route toward an exemplary small molecule, sonidegib, on a modular, robotic flow synthesis platform with integrated process analytical technology (PAT) for data-rich experimentation. Human insights address catalyst deactivation and improve yield by strategic choices of order of addition. Multi-objective Bayesian optimization identifies optimal values for categorical and continuous process variables in the multistep route involving

SUBMITTER: Nambiar AMK 

PROVIDER: S-EPMC9228554 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature