# Fast and scalable retrosynthetic planning with a transformer neural network and speculative beam search

arXiv: https://arxiv.org/abs/2508.01459 · HTML: https://mlsanity.com/paper/2508.01459/

## Key facts

- Cited by 2 papers in the map (data through 14 Oct 2026).
- Builds on 15 of its 29 references that are in the map.
- First posted on arXiv 2 Aug 2025.

## Builds on (most cited first, 15 of 15)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Fast Inference from Transformers via Speculative Decoding](https://mlsanity.com/paper/2211.17192/) (2022)
- [Medusa: Simple LLM Inference Acceleration Framework with Multiple Decoding Heads](https://mlsanity.com/paper/2401.10774/) (2024)
- [Linear Transformers Are Secretly Fast Weight Programmers](https://mlsanity.com/paper/2102.11174/) (2021)
- [Molecular Transformer - A Model for Uncertainty-Calibrated Chemical Reaction Prediction](https://mlsanity.com/paper/1811.02633/) (2018)
- [Learning to Plan Chemical Syntheses](https://mlsanity.com/paper/1708.04202/) (2017)
- [Retro*: Learning Retrosynthetic Planning with Neural Guided A* Search](https://mlsanity.com/paper/2006.15820/) (2020)
- [Root-aligned SMILES: A Tight Representation for Chemical Reaction Prediction](https://mlsanity.com/paper/2203.11444/) (2022)
- [Re-evaluating Retrosynthesis Algorithms with Syntheseus](https://mlsanity.com/paper/2310.19796/) (2023)
- [Models Matter: The Impact of Single-Step Retrosynthesis on Synthesis Planning](https://mlsanity.com/paper/2308.05522/) (2023)
- [Mind the Retrosynthesis Gap: Bridging the divide between Single-step and Multi-step Retrosynthesis Prediction](https://mlsanity.com/paper/2212.11809/) (2022)
- [ASKCOS: an open source software suite for synthesis planning](https://mlsanity.com/paper/2501.01835/) (2025)
- [Accelerating the inference of string generation-based chemical reaction models for industrial applications](https://mlsanity.com/paper/2407.09685/) (2024)

## Built on by (most cited first, 2 of 2)

- [AOT*: Efficient Synthesis Planning via LLM-Empowered AND-OR Tree Search](https://mlsanity.com/paper/2509.20988/) (2025)
- [Project Ariadne: Prompt-Conditioned Route Generation for Synthesis Planning](https://mlsanity.com/paper/2606.24184/) (2026)

## Abstract (arXiv)

AI-based computer-aided synthesis planning (CASP) systems are in demand as components of AI-driven drug discovery workflows. However, the high latency of such CASP systems limits their utility for high-throughput synthesizability screening in de novo drug design. We propose a method for accelerating multi-step synthesis planning systems that rely on SMILES-to-SMILES transformers as single-step retrosynthesis models. Our approach reduces the latency of SMILES-to-SMILES transformers powering multi-step synthesis planning in AiZynthFinder through speculative beam search combined with a scalable drafting strategy called Medusa. Replacing standard beam search with our approach allows the CASP system to solve 26% to 86% more molecules under the same time constraints of several seconds. Our method brings AI-based CASP systems closer to meeting the strict latency requirements of high-throughput synthesizability screening and improving general user experience.