arXiv:2603.12666cs.LGcs.AI2026-03

提出可推理断键策略的智能合成规划模型,提升复杂分子合成路径预测能力。

RetroReasoner: A Reasoning LLM for Strategic Retrosynthesis Prediction

  • 基于断键逻辑构建推理框架,生成带解释的反应物预测
  • 在挑战性反应中生成更多可行反应物,准确率超越主流模型
  • 适合药物研发与化学合成自动化场景使用

逆合成预测旨在识别能合成目标分子的反应物。尽管分子大语言模型近期表现优异,但现有方法多直接生成反应物或仅提供产品层面分析,缺乏对具体反应物选择背后断键策略的显式推理。本文提出RetroReasoner,一种模拟化学家断键策略思维的逆合成推理模型。该模型通过监督微调和强化学习训练:监督微调阶段,SyntheticRetro生成与反应物预测配对的结构化断键解释;强化学习阶段,采用往返奖励机制,通过正向合成模型验证预测反应物能否重构原产物,并奖励成功重建的结果。RetroReasoner还可集成至并行化的蒙特卡洛树搜索框架中,用于多步逆合成规划,显著降低搜索时间的同时提升有效合成路径的数量与多样性。实验表明,RetroReasoner优于先前基线模型,包括通用分子大模型及专门设计的逆合成专家模型,在复杂反应实例中生成更广泛的可行反应物方案。代码已开源:https://github.com/KU-AGI/RetroReasoner。

原文摘要 · Abstract (English)

Retrosynthesis prediction aims to identify reactants that can synthesize a given product molecule. Although molecular large language models (LLMs) have recently shown promising results, most existing methods either generate reactants directly or provide only generic product-level analysis, without explicitly reasoning about bond-disconnection strategies that justify specific reactant choices. This paper proposes RetroReasoner, a retrosynthetic reasoning model that captures chemists' strategic disconnection-based thinking. RetroReasoner is trained with supervised fine-tuning and reinforcement learning. For supervised fine-tuning, SyntheticRetro generates structured disconnection rationales paired with reactant predictions. For reinforcement learning, a round-trip reward evaluates predicted reactants by passing them through a forward synthesis model and rewarding predictions that reconstruct the original product. RetroReasoner can also be applied to multi-step retrosynthetic planning by incorporating it into a parallelized Monte Carlo tree search framework, reducing search time while increasing the number and diversity of valid synthetic pathways. Experimental results show that RetroReasoner outperforms prior baselines, including not only molecular LLMs but also retrosynthesis-specific expert models, and generates a broader range of feasible reactant proposals, especially for challenging reaction instances. The code is available at https://github.com/KU-AGI/RetroReasoner.

逆合成大模型化学智能推理生成

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。