Synthelite: Chemist-aligned and feasibility-aware synthesis planning with LLMs

• URL: http://arxiv.org/abs/2512.16424v1
• Date: Thu, 18 Dec 2025 11:24:30 GMT
• Title: Synthelite: Chemist-aligned and feasibility-aware synthesis planning with LLMs
• Authors: Nguyen Xuan-Vu, Daniel Armstrong, Milena Wehrbach, Andres M Bran, Zlatko Jončev, Philippe Schwaller,
• Abstract summary: We introduce Synthelite, a synthesis planning framework that uses large language models to propose retrosynthetic transformations.<n> Synthelite can generate end-to-end synthesis routes by harnessing the intrinsic chemical knowledge and reasoning capabilities of LLMs.<n>Our experiments demonstrate that Synthelite can flexibly adapt its planning trajectory to diverse user-specified constraints, achieving up to 95% success rates.
• Score: 3.7129661557601854
• License: http://creativecommons.org/licenses/by/4.0/
• Abstract: Computer-aided synthesis planning (CASP) has long been envisioned as a complementary tool for synthetic chemists. However, existing frameworks often lack mechanisms to allow interaction with human experts, limiting their ability to integrate chemists' insights. In this work, we introduce Synthelite, a synthesis planning framework that uses large language models (LLMs) to directly propose retrosynthetic transformations. Synthelite can generate end-to-end synthesis routes by harnessing the intrinsic chemical knowledge and reasoning capabilities of LLMs, while allowing expert intervention through natural language prompts. Our experiments demonstrate that Synthelite can flexibly adapt its planning trajectory to diverse user-specified constraints, achieving up to 95\% success rates in both strategy-constrained and starting-material-constrained synthesis tasks. Additionally, Synthelite exhibits the ability to account for chemical feasibility during route design. We envision Synthelite to be both a useful tool and a step toward a paradigm where LLMs are the central orchestrators of synthesis planning.

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