ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

SE-MCTS: a similarity-based multi-step retrosynthesis route planning model

Cancan Ji, Xiangsheng Huang, Jia Ao, and Wei Dai

College of Materials Science and Opto-Electronic Technology, University of Chinese Academy of Science, Beijing, China

E-mail: jicancan23@mails.ucas.ac.cn

Received: 12 March 2025  Accepted: 16 September 2025

Abstract:

In the field of computer-aided synthesis planning, retrosynthetic pathway planning stands as a core issue. It aims to leverage data-driven strategies to explore synthetic routes that are both efficient and feasible for the target molecule. Current retrosynthesis methods rely on two core components: (a) an effective search methods, such as Monte Carol tree search, heuristic A* search, depth-first search, or breadth-first search; and (b) a useful evaluation methods. However, the existing evaluation methods cannot accurately depict the synthetic cost of molecules. In our study, we introduce a novel strategy for the evaluation of intermediate molecules in multi-step synthesis, namely similarity estimate. This strategy gauges the synthesis complexity of molecules by estimating their prevalence. Experimental results on classical datasets substantiate that our approach can effectively reduce the complexity of path search and augment the interpretability of multi-step retrosynthesis algorithms.

Graphical abstract

Keywords: Retrosynthesis; Monte Carol tree; Rollout; Drug discovery

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04388-8

Chemical Papers 80 (1) 263–271 (2026)