Tango*: Constrained synthesis planning using chemically informed value functions

Abstract

Computer-aided synthesis planning (CASP) has made significant strides in generating retrosynthetic pathways for simple molecules in a non-constrained fashion. Recent work introduces a specialised bidirectional search algorithm with forward and retro expansion to address the starting material-constrained synthesis problem, allowing CASP systems to provide synthesis pathways from specified starting materials. In this work, we introduce a simple guided search—Tango—which allows solving the starting material-constrained synthesis planning problem using an existing uni-directional search algorithm, Retro*. We show that by optimising a single hyperparameter, Tango* outperforms existing methods in terms of efficiency and solve rate. We also highlight the effectiveness of our computed node cost function in steering synthesis pathways.