Title: Computer-assisted Retrosynthesis Based on Molecular Similarity
Authors: Connor W. Coley, Luke Rogers, William H. Green, Klavs F. Jensen
Publication Date: 2017/11/16
Publication Link: ACS Central Science
Alternative Publication Links: DSpace@MIT |
PubMed Central |
ResearchGate
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.