Papers › SynLlama: Generating Synthesizable Molecules and Their Analogs with Large Language Models
SynLlama: Generating Synthesizable Molecules and Their Analogs with Large Language Models
Kunyang Sun, Dorian Bagni, Joseph M. Cavanagh, Yingze Wang, Jacob M. Sawyer, Andrew Gritsevskiy, Oufan Zhang, Teresa Head-Gordon
Generative machine learning models for small molecule drug discovery have shown immense promise, but many molecules they generate are too difficult to synthesize, making them impractical for further investigation or development. In this work, we present a novel approach by fine-tuning Meta's Llama3 Large Language Models (LLMs) to create SynLlama, which generates full synthetic pathways made of commonly accessible building blocks and robust organic reaction templates. SynLlama explores a large synthesizable space using significantly less data compared to other state-of-the-art methods, and offers strong performance in bottom-up synthesis, synthesizable analog generation, and hit expansion, offering medicinal chemists a valuable tool for drug discovery developments. We find that SynLlama, even without training on external building blocks, can effectively generalize to unseen yet purchasable building blocks, meaning that its reconstruction capabilities extend to a broader synthesizable chemical space than the training data. We also demonstrate the use of SynLlama in a pharmaceutical context for synthesis planning of analog molecules and hit expansion leads for proposed inhibitors of target proteins.
In Syntology Open this paper in Syntology's Atlas, the map of the papers in Syntology's graph and their citations.
Code
Repository list and official/mentioned flags are the archive's, frozen 2025-07-28. Reachability, where shown, is from one Syntology probe window (2026-09-16 to 2026-09-18); repositories not probed show nothing. GitHub stars are not tracked.
Code Syntology ran Syntology
Not run by Syntology. Nothing on this page verifies that the listed code works.
Tasks
Results from the paper archive 2025-07-28
No leaderboard rows for this paper in the archive.
Report a problem or propose a change · a person checks every report against the paper or source before anything changes; decisions are listed on /corrections