Prediction of higher-selectivity catalysts by computer-driven workflow and machine learning

Catalyst design in asymmetric reaction development has traditionally been driven by empiricism, wherein experimentalists attempt to qualitatively recognize structural patterns to improve selectivity. Machine learning algorithms and chemoinformatics can potentially accelerate this process by recogniz...

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Published inScience (American Association for the Advancement of Science) Vol. 363; no. 6424
Main Authors Zahrt, Andrew F, Henle, Jeremy J, Rose, Brennan T, Wang, Yang, Darrow, William T, Denmark, Scott E
Format Journal Article
LanguageEnglish
Published United States 18.01.2019
Online AccessGet full text
ISSN1095-9203
0036-8075
1095-9203
DOI10.1126/science.aau5631

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Abstract Catalyst design in asymmetric reaction development has traditionally been driven by empiricism, wherein experimentalists attempt to qualitatively recognize structural patterns to improve selectivity. Machine learning algorithms and chemoinformatics can potentially accelerate this process by recognizing otherwise inscrutable patterns in large datasets. Herein we report a computationally guided workflow for chiral catalyst selection using chemoinformatics at every stage of development. Robust molecular descriptors that are agnostic to the catalyst scaffold allow for selection of a universal training set on the basis of steric and electronic properties. This set can be used to train machine learning methods to make highly accurate predictive models over a broad range of selectivity space. Using support vector machines and deep feed-forward neural networks, we demonstrate accurate predictive modeling in the chiral phosphoric acid-catalyzed thiol addition to -acylimines.
AbstractList Catalyst design in asymmetric reaction development has traditionally been driven by empiricism, wherein experimentalists attempt to qualitatively recognize structural patterns to improve selectivity. Machine learning algorithms and chemoinformatics can potentially accelerate this process by recognizing otherwise inscrutable patterns in large datasets. Herein we report a computationally guided workflow for chiral catalyst selection using chemoinformatics at every stage of development. Robust molecular descriptors that are agnostic to the catalyst scaffold allow for selection of a universal training set on the basis of steric and electronic properties. This set can be used to train machine learning methods to make highly accurate predictive models over a broad range of selectivity space. Using support vector machines and deep feed-forward neural networks, we demonstrate accurate predictive modeling in the chiral phosphoric acid-catalyzed thiol addition to -acylimines.
Author Wang, Yang
Rose, Brennan T
Darrow, William T
Henle, Jeremy J
Denmark, Scott E
Zahrt, Andrew F
Author_xml – sequence: 1
  givenname: Andrew F
  orcidid: 0000-0002-1835-5163
  surname: Zahrt
  fullname: Zahrt, Andrew F
  organization: Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
– sequence: 2
  givenname: Jeremy J
  orcidid: 0000-0001-9045-1726
  surname: Henle
  fullname: Henle, Jeremy J
  organization: Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
– sequence: 3
  givenname: Brennan T
  orcidid: 0000-0002-7225-3600
  surname: Rose
  fullname: Rose, Brennan T
  organization: Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
– sequence: 4
  givenname: Yang
  orcidid: 0000-0002-7584-6188
  surname: Wang
  fullname: Wang, Yang
  organization: Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
– sequence: 5
  givenname: William T
  orcidid: 0000-0002-4784-0133
  surname: Darrow
  fullname: Darrow, William T
  organization: Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
– sequence: 6
  givenname: Scott E
  orcidid: 0000-0002-1099-9765
  surname: Denmark
  fullname: Denmark, Scott E
  email: sdenmark@illinois.edu
  organization: Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, IL 61801, USA. sdenmark@illinois.edu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30655414$$D View this record in MEDLINE/PubMed
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Snippet Catalyst design in asymmetric reaction development has traditionally been driven by empiricism, wherein experimentalists attempt to qualitatively recognize...
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Title Prediction of higher-selectivity catalysts by computer-driven workflow and machine learning
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