Metro: Memory-Enhanced Transformer for Retrosynthetic Planning via Reaction Tree

Retrosynthetic planning plays a critical role in drug discovery and organic chemistry. Starting from a target molecule as the root node, it aims to find a complete reaction tree subject to the constraint that all leaf nodes belong to a set of starting materials. The multi-step reactions are crucial because they determine the flow chart in the production of the Organic Chemical Industry. However, existing datasets lack curation of tree-structured multi-step reactions, and fail to provide such reaction trees, limiting models' understanding of organic molecule transformations. In this work, we first develop a benchmark curated for the retrosynthetic planning task, which consists of 124,869 reaction trees retrieved from the public USPTO-full dataset. On top of that, we propose Metro: Memory-Enhanced Transformer for RetrOsynthetic planning. Specifically, the dependency among molecules in the reaction tree is captured as context information for multi-step retrosynthesis predictions through transformers with a memory module. Extensive experiments show that Metro dramatically outperforms existing single-step retrosynthesis models by at least 10.7% in top-1 accuracy. The experiments demonstrate the superiority of exploiting context information in the retrosynthetic planning task. Moreover, the proposed model can be directly used for synthetic accessibility analysis, as it is trained on reaction trees with the shortest depths. Our work is the first step towards a brand new formulation for retrosynthetic planning in the aspects of data construction, model design, and evaluation. Code is available at https://github.com/SongtaoLiu0823/metro.