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

Andrea Byekwaso, Philippe Schwaller, Alain C. Vaucher, Alessandra Toniato, Teodoro Laino

Keywords: Chemistry, Retrosynthesis, Transformer

Abstract: 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 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 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.

Track: Original Research Track

TL;DR: Combine the strength of AI and expert chemists for single-step retro-synthesis