A User-Tunable Machine Learning Framework for Step-Wise Synthesis Planning

Fuente: arXiv
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Main Authors: Prakash, Shivesh, Patel, Nandan, Jacobsen, Hans-Arno, Prasad, Viki Kumar
Format: Preprint
Published: 2025
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author Prakash, Shivesh
Patel, Nandan
Jacobsen, Hans-Arno
Prasad, Viki Kumar
author_facet Prakash, Shivesh
Patel, Nandan
Jacobsen, Hans-Arno
Prasad, Viki Kumar
contents We introduce MHNpath, a machine learning-driven retrosynthetic tool designed for computer-aided synthesis planning. Leveraging modern Hopfield networks and novel comparative metrics, MHNpath efficiently prioritizes reaction templates, improving the scalability and accuracy of retrosynthetic predictions. The tool incorporates a tunable scoring system that allows users to prioritize pathways based on cost, reaction temperature, and toxicity, thereby facilitating the design of greener and cost-effective reaction routes. We demonstrate its effectiveness through case studies involving complex molecules from ChemByDesign, showcasing its ability to predict novel synthetic and enzymatic pathways. Furthermore, we benchmark MHNpath against existing frameworks using the PaRoutes dataset, achieving a solution rate of 85.4% and replicating 69.2% of experimentally validated "gold-standard" pathways. Our case studies reveal that the tool can generate shorter, cheaper, moderate-temperature routes employing green solvents, as exemplified by compounds such as dronabinol, arformoterol, and lupinine.
format Preprint
id arxiv_https___arxiv_org_abs_2504_02191
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle A User-Tunable Machine Learning Framework for Step-Wise Synthesis Planning
Prakash, Shivesh
Patel, Nandan
Jacobsen, Hans-Arno
Prasad, Viki Kumar
Computational Engineering, Finance, and Science
Machine Learning
We introduce MHNpath, a machine learning-driven retrosynthetic tool designed for computer-aided synthesis planning. Leveraging modern Hopfield networks and novel comparative metrics, MHNpath efficiently prioritizes reaction templates, improving the scalability and accuracy of retrosynthetic predictions. The tool incorporates a tunable scoring system that allows users to prioritize pathways based on cost, reaction temperature, and toxicity, thereby facilitating the design of greener and cost-effective reaction routes. We demonstrate its effectiveness through case studies involving complex molecules from ChemByDesign, showcasing its ability to predict novel synthetic and enzymatic pathways. Furthermore, we benchmark MHNpath against existing frameworks using the PaRoutes dataset, achieving a solution rate of 85.4% and replicating 69.2% of experimentally validated "gold-standard" pathways. Our case studies reveal that the tool can generate shorter, cheaper, moderate-temperature routes employing green solvents, as exemplified by compounds such as dronabinol, arformoterol, and lupinine.
title A User-Tunable Machine Learning Framework for Step-Wise Synthesis Planning
topic Computational Engineering, Finance, and Science
Machine Learning
url https://arxiv.org/abs/2504.02191