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Self-Improved Retrosynthetic Planning

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arxiv 2106.04880 v1 pith:KKU5SPNY submitted 2021-06-09 cs.LG q-bio.QM

Self-Improved Retrosynthetic Planning

classification cs.LG q-bio.QM
keywords reactionpathwaysproblemreactionsretrosyntheticdnnsplanningexpand
verification ladder T0 review T1 audit T2 compute T3 formal T4 reserved
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Retrosynthetic planning is a fundamental problem in chemistry for finding a pathway of reactions to synthesize a target molecule. Recently, search algorithms have shown promising results for solving this problem by using deep neural networks (DNNs) to expand their candidate solutions, i.e., adding new reactions to reaction pathways. However, the existing works on this line are suboptimal; the retrosynthetic planning problem requires the reaction pathways to be (a) represented by real-world reactions and (b) executable using "building block" molecules, yet the DNNs expand reaction pathways without fully incorporating such requirements. Motivated by this, we propose an end-to-end framework for directly training the DNNs towards generating reaction pathways with the desirable properties. Our main idea is based on a self-improving procedure that trains the model to imitate successful trajectories found by itself. We also propose a novel reaction augmentation scheme based on a forward reaction model. Our experiments demonstrate that our scheme significantly improves the success rate of solving the retrosynthetic problem from 86.84% to 96.32% while maintaining the performance of DNN for predicting valid reactions.

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Cited by 5 Pith papers

Reviewed papers in the Pith corpus that reference this work. Sorted by Pith novelty score.

  1. Agentic generation of verifiable rules for deterministic, self-expanding reaction classification

    cs.AI 2026-07 unverdicted novelty 7.0

    Multi-agent LLMs generate and verify 14,073 deterministic reaction rules from 665,901 patents, enabling 97.7% classification of unseen reactions with finer resolution than fixed proprietary systems.

  2. Agentic generation of verifiable rules for deterministic, self-expanding reaction classification

    cs.AI 2026-07 conditional novelty 7.0

    Multi-agent LLMs classify USPTO reactions and write verified SMIRKS rules, expanding a 68-class taxonomy to 14,073 and classifying 97.7% of held-out reactions with a hybrid fingerprint-plus-template system.

  3. Agentic generation of verifiable rules for deterministic, self-expanding reaction classification

    cs.AI 2026-07 conditional novelty 7.0

    Multi-agent LLMs classify USPTO reactions and write verified SMIRKS rules, expanding a reaction taxonomy from 68 to 14,073 classes and matching proprietary classifiers on held-out and out-of-distribution data.

  4. MMORF: A Multi-agent Framework for Designing Multi-objective Retrosynthesis Planning Systems

    cs.AI 2026-04 unverdicted novelty 7.0

    MMORF provides a modular multi-agent framework for multi-objective retrosynthesis planning, with MASIL and RFAS systems showing strong safety, cost, and success metrics on a new 218-task benchmark.

  5. URSA: Chemistry-Aware Benchmark for Utilitarian Retrosynthesis Assessment

    cs.LG 2026-07 accept novelty 6.0

    Specialized retrosynthesis models outperform LLMs on chemically plausible multi-step routes when scored by the new URSA Solv-2 protocol using ChemCensor.