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 has introduced specialized bidirectional search algorithms to find synthesis pathways that incorporate pre-selected starting materials, tackling a specific formulation of the starting material-constrained problem. In this work, we introduce a simple guided search—Tango*-which allows solving the starting material-constrained synthesis planning problem using an existing unidirectional 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.