Skip to yearly menu bar Skip to main content

Workshop: AI for Science: Mind the Gaps

Human-in-the-loop for a Disconnection Aware Retrosynthesis

Andrea Byekwaso · Philippe Schwaller · Alain C. Vaucher · Teodoro Laino


Retrosynthesis is an approach commonly undertaken when considering the manufacture of novel molecules. During this process, a target molecule is broken down and analyzed by considering the bonds to be changed as well as the functional group interconversion. In modern computer-assisted synthesis planning tools, the predictions of these changes are typically carried out automatically. However there may be some benefit to the decision being guided by to those executing the process: typically, chemists have a clear idea where the retrosynthetic change should happen, but not how such a transformation is to be realized. Using a data-driven model, the retrosynthesis task can be further explored by giving chemists the option to explore specific disconnections. In this work, we design an approach to provide this option to those carrying out retrosynthetic analysis by adapting a transformer-based model for single-step retrosynthesis. The model takes as input a product SMILES string, in which the atoms where the transformation should occur are tagged accordingly. This model predicts precursors corresponding to a disconnection occurring in the correct location in 88.9\% of the test set reactions. The assessment with a forward prediction model shows that 76\% of the predictions are chemically correct, with 14.1\% perfectly matching the ground truth.