Project Ariadne Generates Synthesis Routes with Prompt Conditioning.

Researchers have introduced Project Ariadne, a novel decoder-only route generator designed for chemical synthesis planning. This system reframes retrosynthesis—the process of working backward from a target molecule to available starting materials—as a sequence generation task. Unlike previous direct-generation methods that require separate models for different planning specifications, Ariadne uses a single prompt-completion sequence to represent the target molecule, optional constraints, and the resulting synthesis route. The model, a 24-layer checkpoint, demonstrates strong performance on the RetroCast/PaRoutes mkt-cnv-160 benchmark family. By adding prompt fields for route depth and required starting materials, Ariadne significantly improves solution rates (Solv-0) by 13.7 points for depth constraints and 31.2 points for required-leaf constraints. Ariadne also outperforms DESP, a bidirectional search planner, in terms of required-leaf Top-10 and Solv-0, achieving results in significantly less GPU time. While comparable to DMS Explorer XL for standard reconstruction, Ariadne shows clearer gains on route-holdout reconstruction. This work extends sequence generation capabilities to prompt-conditioned structural route generation, offering a more flexible and efficient approach to retrosynthetic planning.