Synthesis Route Identification and Prioritization in Reaction Knowledge Graphs

Identifying synthesis routes from knowledge graphs poses challenges beyond retrosynthesis, including path–finding artifacts and data issues. We introduce “SynGPS”, a novel algorithm that overcomes these limitations by identifying viable routes even with common artifacts. SynGPS can resolve nonsensical cycles, disconnect misleading links to starting materials, and remove ambiguous reactions, relying solely on topological heuristics for flexible scoring. We also present the Backtracking–Oriented Yield Aggregation (BOYA) algorithm, a new molar ratio–based method for calculating synthesis yield that addresses the molecular weight biases of existing weight-based approaches. Case studies demonstrate the effectiveness of SynGPS and BOYA algorithms, and we provide a rigorous theoretical framework that can facilitate the comparison of existing and future methods in the field of computer—aided synthesis planning (CASP).