Automatic retrosynthetic route planning using template-free models.

Chemical Science
Kangjie LinLuhua Lai

Abstract

Retrosynthetic route planning can be considered a rule-based reasoning procedure. The possibilities for each transformation are generated based on collected reaction rules, and then potential reaction routes are recommended by various optimization algorithms. Although there has been much progress in computer-assisted retrosynthetic route planning and reaction prediction, fully data-driven automatic retrosynthetic route planning remains challenging. Here we present a template-free approach that is independent of reaction templates, rules, or atom mapping, to implement automatic retrosynthetic route planning. We treated each reaction prediction task as a data-driven sequence-to-sequence problem using the multi-head attention-based Transformer architecture, which has demonstrated power in machine translation tasks. Using reactions from the United States patent literature, our end-to-end models naturally incorporate the global chemical environments of molecules and achieve remarkable performance in top-1 predictive accuracy (63.0%, with the reaction class provided) and top-1 molecular validity (99.6%) in one-step retrosynthetic tasks. Inspired by the success rate of the one-step reaction prediction, we further carried out iterative...Continue Reading

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Citations

Dec 30, 2020·Journal of Cheminformatics·Fernanda I Saldívar-GonzálezJosé L Medina-Franco
Jan 13, 2021·Journal of Cheminformatics·Umit V UcakJuyong Lee
Feb 21, 2021·Drug Discovery Today·Jiacheng XiongMingyue Zheng
Mar 16, 2021·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Angelo Albini
Apr 20, 2021·Expert Opinion on Drug Discovery·W Patrick Walters, Regina Barzilay
Jun 25, 2021·Chemical Science·Yiming MoKlavs F Jensen
Nov 6, 2020·Nature Communications·Igor V TetkoGuillaume Godin
Jul 13, 2021·Journal of Chemical Information and Modeling·Mikołaj SachaStanisław Jastrzębski
Aug 4, 2021·Journal of Chemical Information and Modeling·Samuel GenhedenEsben Bjerrum
Jun 23, 2020·Journal of Chemical Information and Modeling·Michael E FortunatoKlavs F Jensen
Jan 8, 2021·Journal of Chemical Information and Modeling·Eunji KimYoun-Suk Choi
Sep 26, 2020·Journal of Chemical Information and Modeling·Zhongliang GuoRyo Yoshida
Sep 28, 2021·Briefings in Bioinformatics·Jingxin DongXiangxiang Zeng
Sep 25, 2021·Angewandte Chemie·Sara SzymkućBartosz A Grzybowski
Nov 12, 2021·Journal of Chemical Information and Modeling·Grigorii V AndrianovJohn Karanicolas

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Methods Mentioned

BETA
seq2seq

Software Mentioned

MCTS
TensorFlow
SMILES
Synthia
Chematica
seq2seq
LHASA
RDKit
AutoSynRoute

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