Papers › DirectMultiStep: Direct Route Generation for Multi-Step Retrosynthesis

DirectMultiStep: Direct Route Generation for Multi-Step Retrosynthesis

22 May 2024arXiv:2405.13983archive 2025-07-28

Yu Shee, Haote Li, Anton Morgunov, Victor Batista

Traditional computer-aided synthesis planning (CASP) methods rely on iterative single-step predictions, leading to exponential search space growth that limits efficiency and scalability. We introduce a series of transformer-based models, utilizing mixture of experts approach, that directly generate multistep synthetic routes as a single string by conditionally predicting each molecule based on all preceding ones. Our models can accommodate specific conditions such as the desired number of steps and starting materials, with the top-performing DMS-Flex (Duo) surpassing state-of-the-art methods on the PaRoutes dataset with a 2.5x improvement in Top-1 accuracy on the n₁ test set and a 3.9x improvement on the n₅ test set. It also successfully predicts routes for FDA-approved drugs not included in the training data, showcasing its generalization capabilities. While the current suboptimal diversity of the training set may impact performance on less common reaction types, our multistep-first approach presents a promising direction towards fully automated retrosynthetic planning.

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DiversityMixture-of-ExpertsMulti-step retrosynthesisRetrosynthesis

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