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 |
| Published: |
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 |
| Summary: | 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. |
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