# Template-Free Retrosynthesis with Graph-Prior Augmented Transformers

arXiv: https://arxiv.org/abs/2512.10770 · HTML: https://mlsanity.com/paper/2512.10770/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 9 of its 22 references that are in the map.
- First posted on arXiv 11 Dec 2025.

## Builds on (most cited first, 9 of 9)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Retrosynthesis Prediction with Conditional Graph Logic Network](https://mlsanity.com/paper/2001.01408/) (2020)
- [Molecule Edit Graph Attention Network: Modeling Chemical Reactions as Sequences of Graph Edits](https://mlsanity.com/paper/2006.15426/) (2020)
- [Retrosynthetic reaction prediction using neural sequence-to-sequence models](https://mlsanity.com/paper/1706.01643/) (2017)
- [A Graph to Graphs Framework for Retrosynthesis Prediction](https://mlsanity.com/paper/2003.12725/) (2020)
- [RetroXpert: Decompose Retrosynthesis Prediction like a Chemist](https://mlsanity.com/paper/2011.02893/) (2020)
- [Permutation invariant graph-to-sequence model for template-free retrosynthesis and reaction prediction](https://mlsanity.com/paper/2110.09681/) (2021)
- [Root-aligned SMILES: A Tight Representation for Chemical Reaction Prediction](https://mlsanity.com/paper/2203.11444/) (2022)
- [OpenNMT: Neural Machine Translation Toolkit](https://mlsanity.com/paper/1805.11462/) (2018)

## Abstract (arXiv)

Retrosynthesis reaction prediction aims to infer plausible reactant molecules for a given product and is a important problem in computer-aided organic synthesis. Despite recent progress, many existing models still fall short of the accuracy and robustness required for practical deployment. In this paper, we present a template-free, Transformer-based framework that removes the need for handcrafted reaction templates or additional chemical rule engines. Our model injects molecular graph information into the attention mechanism to jointly exploit SMILES sequences and structural cues, and further applies a paired data augmentation strategy to enhance training diversity and scale. Extensive experiments on the USPTO-50K benchmark demonstrate that our approach achieves state-of-the-art performance among template-free methods and substantially outperforms a vanilla Transformer baseline.