RETRO SYNFLOW: Discrete Flow-Matching for Accurate and Diverse Single-Step Retrosynthesis

A fundamental challenge in organic chemistry is identifying and predicting the sequence of reactions that synthesize a desired target molecule. Due to the combinatorial nature of the chemical search space, single-step reactant prediction--i.e., single-step retrosynthesis--remains difficult, even for state-of-the-art template-free generative methods. These models often struggle to produce an accurate yet diverse set of feasible reactions in a chemically rational manner. In this paper, we propose RETRO SYNFLOW (RSF), a discrete flow-matching framework that formulates single-step retrosynthesis as a Markov bridge between a given product molecule and its corresponding reactants. Unlike prior approaches, RSF introduces a reaction center identification step to extract intermediate structures, or synthons, which serve as a more informative and structured source distribution for the discrete flow model.