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The advancement of machine learning and the availability of large-scale reaction datasets have accelerated the development of data-driven models for computer-aided synthesis planning (CASP) in the past decade. Here, we detail the newest…

Template-free SMILES-to-SMILES translation models for reaction prediction and single-step retrosynthesis are of interest for industrial applications in computer-aided synthesis planning systems due to their state-of-the-art accuracy.…

Machine Learning · Computer Science 2024-07-18 Mikhail Andronov , Natalia Andronova , Michael Wand , Jürgen Schmidhuber , Djork-Arné Clevert

The field of computer-aided synthesis planning (CASP) has seen rapid advancements in recent years, achieving significant progress across various algorithmic benchmarks. However, chemists often encounter numerous infeasible reactions when…

Machine Learning · Computer Science 2024-09-09 Shang Xiang , Lin Yao , Zhen Wang , Qifan Yu , Wentan Liu , Wentao Guo , Guolin Ke

Retrosynthesis analysis is pivotal yet challenging in drug discovery and organic chemistry. Despite the proliferation of computational tools over the past decade, AI-based systems often fall short in generalizing across diverse reaction…

Machine Learning · Computer Science 2024-08-21 Yifei Yang , Runhan Shi , Zuchao Li , Shu Jiang , Bao-Liang Lu , Yang Yang , Hai Zhao

From medicines to materials, small organic molecules are indispensable for human well-being. To plan their syntheses, chemists employ a problem solving technique called retrosynthesis. In retrosynthesis, target molecules are recursively…

Artificial Intelligence · Computer Science 2018-04-17 Marwin H. S. Segler , Mike Preuss , Mark P. Waller

Motivation: Retrosynthesis planning poses a formidable challenge in the organic chemical industry. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to…

Chemical Physics · Physics 2024-04-22 Kaipeng Zeng , Bo yang , Xin Zhao , Yu Zhang , Fan Nie , Xiaokang Yang , Yaohui Jin , Yanyan Xu

We present an attention-based Transformer model for automatic retrosynthesis route planning. Our approach starts from reactants prediction of single-step organic reactions for given products, followed by Monte Carlo tree search-based…

Quantitative Methods · Quantitative Biology 2019-06-07 Kangjie Lin , Youjun Xu , Jianfeng Pei , Luhua Lai

Computer-aided synthesis planning (CASP) algorithms have demonstrated expert-level abilities in planning retrosynthetic routes to molecules of low to moderate complexity. However, current search methods assume the sufficiency of reaching…

Artificial Intelligence · Computer Science 2024-11-04 Kevin Yu , Jihye Roh , Ziang Li , Wenhao Gao , Runzhong Wang , Connor W. Coley

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…

Artificial Intelligence · Computer Science 2025-12-19 Nguyen Xuan-Vu , Daniel Armstrong , Milena Wehrbach , Andres M Bran , Zlatko Jončev , Philippe Schwaller

Retrosynthesis prediction is fundamental to drug discovery and chemical synthesis, requiring the identification of reactants that can produce a target molecule. Current template-free methods struggle to capture the structural invariance…

Machine Learning · Computer Science 2025-10-21 Jiaxi Zhuang , Yu Zhang , Aimin Zhou , Ying Qian

Synthesis planning is the process of recursively decomposing target molecules into available precursors. Computer-aided retrosynthesis can potentially assist chemists in designing synthetic routes, but at present it is cumbersome and…

Chemical Physics · Physics 2019-07-04 Shuangjia Zheng , Jiahua Rao , Zhongyue Zhang , Jun Xu , Yuedong Yang

Chemical synthesis remains a critical bottleneck in the discovery and manufacture of functional small molecules. AI-based synthesis planning models could be a potential remedy to find effective syntheses, and have made progress in recent…

Modern computer-assisted synthesis planning (CASP) systems show promises at generating chemically valid reaction steps but struggle to incorporate strategic considerations such as convergent assembly, protecting group minimization, and…

Artificial Intelligence · Computer Science 2025-12-02 Daniel Armstrong , Zlatko Jončev , Andres M Bran , Philippe Schwaller

Traditional computer-aided synthesis planning (CASP) methods rely on iterative single-step predictions, leading to exponential search space growth that limits efficiency and scalability. We introduce a series of transformer-based models,…

Machine Learning · Computer Science 2025-04-09 Yu Shee , Anton Morgunov , Haote Li , Victor S. Batista

Computer-aided synthesis planning (CASP) has made significant strides in generating retrosynthetic pathways for simple molecules in a non-constrained fashion. Recent work introduces a specialised bidirectional search algorithm with forward…

Computational Engineering, Finance, and Science · Computer Science 2024-12-05 Daniel Armstrong , Zlatko Joncev , Jeff Guo , Philippe Schwaller

Artificial intelligence (AI) is increasingly used in every stage of drug development. One challenge facing drug discovery AI is that drug pharmacokinetic (PK) datasets are often collected independently from each other, often with limited…

Quantitative Methods · Quantitative Biology 2025-07-03 Bing Hu , Anita Layton , Helen Chen

Constraint answer set programming or CASP, for short, is a hybrid approach in automated reasoning putting together the advances of distinct research areas such as answer set programming, constraint processing, and satisfiability modulo…

Artificial Intelligence · Computer Science 2021-07-20 Yuliya Lierler

The identification of synthetic routes that end with a desired product has been an inherently time-consuming process that is largely dependent on expert knowledge regarding a limited fraction of the entire reaction space. At present,…

Machine Learning · Statistics 2020-12-17 Zhongliang Guo , Stephen Wu , Mitsuru Ohno , Ryo Yoshida

The disconnect between AI-generated molecules with desirable properties and their synthetic feasibility remains a critical bottleneck in computational discovery of drugs and materials. While generative AI has accelerated the proposal of…

Chemical Physics · Physics 2025-11-25 Shuan Chen , Gunwook Nam , Alan Aspuru-Guzik , Yousung Jung

Chemical reaction mechanisms are the foundation of how chemists evaluate reactivity and feasibility, yet current Computer-Assisted Synthesis Planning (CASP) systems operate without this mechanistic reasoning. We introduce a computational…

Machine Learning · Computer Science 2026-04-20 Théo A. Neukomm , Zlatko Jončev , Philippe Schwaller
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