Similarity based functionalization for enumeration of synthetically plausible chemical libraries surrounding a target
Author(s)
Sankaranarayanan, Karthik
Jensen, Klavs F.
Date Issued
June 6, 2024
Journal
Chemical Science
Publisher
Royal Society of Chemistry
Citation
Chem. Sci., 2024,15, 10221-10231
Version
Final published version
Abstract
Functionalization of lead compounds to create analogs is a challenging step in discovering new molecules with desired properties and it is conducted throughout the chemical industry, including pharmaceuticals and agrochemicals. The process can be time-consuming and expensive, requiring expert intuition and experience. To help address synthesis planning challenges in late-stage functionalization, we have developed a molecular similarity approach that proposes single-step functionalization reactions based on analogy to precedent reactions. The developed approach mimics reaction strategies and suggests co-reactants defined implicitly by a corpus of known reactions. Using ca. 348 k reactions from the patent literature as a knowledge base, the recorded products or close analogs are among the top 20 proposed products in 74% of ∼44 k test reactions. The combinatorial growth inherent in recursive applications of the tool allows the enumeration of chemical libraries surrounding a target compound of interest. Moreover, each step of the resulting library synthesis leverages common chemical transformations reported in the literature accessible to most chemists.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1039/D4SC00523F
