The RScore, or Retrosynthetic Score, is a composite score that ranks proposed synthetic routes by assessing each step’s likelihood based on context, penalizing longer sequences, and favoring similarity to literature precedents, route convergence, and model confidence—with scores ranging from 0 to 1, where 1 indicates an exact literature match. Generally, we recommend a threshold of >= 0.5.

Spaya uses a chiral pool approach to retain stereocenters from commercially available starting material. If Spaya cannot identify a chiral route, it is recommended to remove chirality from the initial structure.

If Spaya cannot identify a route, it is recommended to iteratively relax system constraints. In default mode, the number of steps is set to 10. First, adjust the number of steps to 15, then remove advanced parameters and/or chirality, before reinitiating retrosynthesis.

Occasionally, due to the difficulty in extracting patent information, Spaya may not provide precise conditions. It is recommended to review the patent in detail outside of Spaya, using the patent number provided.

Substructure searching identifies molecules containing a specific chemical fragment within a database, while retrosynthetic analysis breaks down a target molecule into simpler starting materials to plan a synthetic route.

1. Integrating synthetic accessibility with AI-based generative drug design, Journal of Cheminformatics volume 15, Article number: 83 (2023).

2. Predicting the Price of Molecules Using Their Predicted Synthetic Pathways, Molecular Informatics, Volume44, February 2025.