Combining retrosynthesis and mixed-integer optimization for minimizing the chemical inventory needed to realize a WHO essential medicines list
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c9re00348g.pdf
Size
1.8 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Gao, Hanyu
Coley, Connor Wilson
Struble, Thomas J
Li, Linyan
Qian, Yujie
Green Jr, William H
Jensen, Klavs F
Date Issued
January 2020
Journal
Reaction Chemistry & Engineering
Publisher
Royal Society of Chemistry (RSC)
Citation
Gao, Hanyo et al. "Combining retrosynthesis and mixed-integer optimization for minimizing the chemical inventory needed to realize a WHO essential medicines list." Reaction Chemistry & Engineering 5, 2 (January 2020): 367-376 © 2020 Royal Society of Chemistry
Version
Final published version
Abstract
The access to essential medicines remains a problem in many low-income countries for logistic and expiration limits, among other factors. Enabling flexible replenishment and easier supply chain management by on demand manufacturing from stored starting materials provides a solution to this challenge. Recent developments in computer-aided chemical synthesis planning have benefited from machine learning in different aspects. In this manuscript, we use those techniques to perform a combined analysis of a WHO essential medicines list to identify synthetic routes that minimize chemical inventory that would be required to synthesize the all the active pharmaceutical ingredients. We use a synthesis planning tool to perform retrosynthetic analyses for 99 targets and solve a mixed-integer programming problem to select a combination of pathways that uses the minimal number of chemicals. This work demonstrates the technical feasibility of reducing storage of active pharmaceutical ingredients to a minimal inventory of starting materials.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Terms of Use
Creative Commons Attribution 3.0 unported license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1039/c9re00348g
