Computer-Assisted Retrosynthesis Based on Molecular Similarity
We demonstrate molecular similarity to be a surprisingly effective metric for proposing and ranking one-step retrosynthetic disconnections based on analogy to precedent reactions. The developed approach mimics the retrosynthetic strategy defined implicitly by a corpus of known reactions without the...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
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American Chemical Society (ACS)
2018
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| Online Access: | http://hdl.handle.net/1721.1/117536 https://orcid.org/0000-0002-8271-8723 https://orcid.org/0000-0003-2603-9694 https://orcid.org/0000-0001-7192-580X |
| _version_ | 1826200283927019520 |
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| author | Coley, Connor Wilson Rogers, Luke Green Jr, William H Jensen, Klavs F |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Coley, Connor Wilson Rogers, Luke Green Jr, William H Jensen, Klavs F |
| author_sort | Coley, Connor Wilson |
| collection | MIT |
| description | We demonstrate molecular similarity to be a surprisingly effective metric for proposing and ranking one-step retrosynthetic disconnections based on analogy to precedent reactions. The developed approach mimics the retrosynthetic strategy defined implicitly by a corpus of known reactions without the need to encode any chemical knowledge. Using 40 000 reactions from the patent literature as a knowledge base, the recorded reactants are among the top 10 proposed precursors in 74.1% of 5000 test reactions, providing strong quantitative support for our methodology. Extension of the one-step strategy to multistep pathway planning is demonstrated and discussed for two exemplary drug products. |
| first_indexed | 2024-09-23T11:34:07Z |
| format | Article |
| id | mit-1721.1/117536 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:34:07Z |
| publishDate | 2018 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1175362022-10-01T04:30:30Z Computer-Assisted Retrosynthesis Based on Molecular Similarity Coley, Connor Wilson Rogers, Luke Green Jr, William H Jensen, Klavs F Massachusetts Institute of Technology. Department of Chemical Engineering Coley, Connor Wilson Rogers, Luke Green Jr, William H Jensen, Klavs F We demonstrate molecular similarity to be a surprisingly effective metric for proposing and ranking one-step retrosynthetic disconnections based on analogy to precedent reactions. The developed approach mimics the retrosynthetic strategy defined implicitly by a corpus of known reactions without the need to encode any chemical knowledge. Using 40 000 reactions from the patent literature as a knowledge base, the recorded reactants are among the top 10 proposed precursors in 74.1% of 5000 test reactions, providing strong quantitative support for our methodology. Extension of the one-step strategy to multistep pathway planning is demonstrated and discussed for two exemplary drug products. United States. Army Research Office (Contract W911NF-16-2-0023) National Science Foundation (U.S.) (Grant 1122374) 2018-08-27T14:51:40Z 2018-08-27T14:51:40Z 2017-12 2017-08 2018-08-24T11:44:22Z Article http://purl.org/eprint/type/JournalArticle 2374-7943 2374-7951 http://hdl.handle.net/1721.1/117536 Coley, Connor W. et al. “Computer-Assisted Retrosynthesis Based on Molecular Similarity.” ACS Central Science 3, 12 (November 2017): 1237–1245 © 2017 American Chemical Society https://orcid.org/0000-0002-8271-8723 https://orcid.org/0000-0003-2603-9694 https://orcid.org/0000-0001-7192-580X http://dx.doi.org/10.1021/ACSCENTSCI.7B00355 ACS Central Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) ACS |
| spellingShingle | Coley, Connor Wilson Rogers, Luke Green Jr, William H Jensen, Klavs F Computer-Assisted Retrosynthesis Based on Molecular Similarity |
| title | Computer-Assisted Retrosynthesis Based on Molecular Similarity |
| title_full | Computer-Assisted Retrosynthesis Based on Molecular Similarity |
| title_fullStr | Computer-Assisted Retrosynthesis Based on Molecular Similarity |
| title_full_unstemmed | Computer-Assisted Retrosynthesis Based on Molecular Similarity |
| title_short | Computer-Assisted Retrosynthesis Based on Molecular Similarity |
| title_sort | computer assisted retrosynthesis based on molecular similarity |
| url | http://hdl.handle.net/1721.1/117536 https://orcid.org/0000-0002-8271-8723 https://orcid.org/0000-0003-2603-9694 https://orcid.org/0000-0001-7192-580X |
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