Finding the K best synthesis plans

Rolf Fagerberg, Christoph Flamm, Rojin Kianian, Daniel Merkle, Peter F. Stadler*

*Corresponding author for this work

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Abstract

In synthesis planning, the goal is to synthesize a target molecule from available starting materials, possibly optimizing costs such as price or environmental impact of the process. Current algorithmic approaches to synthesis planning are usually based on selecting a bond set and finding a single good plan among those induced by it. We demonstrate that synthesis planning can be phrased as a combinatorial optimization problem on hypergraphs by modeling individual synthesis plans as directed hyperpaths embedded in a hypergraph of reactions (HoR) representing the chemistry of interest. As a consequence, a polynomial time algorithm to find the K shortest hyperpaths can be used to compute the K best synthesis plans for a given target molecule. Having K good plans to choose from has many benefits: it makes the synthesis planning process much more robust when in later stages adding further chemical detail, it allows one to combine several notions of cost, and it provides a way to deal with imprecise yield estimates. A bond set gives rise to a HoR in a natural way. However, our modeling is not restricted to bond set based approaches—any set of known reactions and starting materials can be used to define a HoR. We also discuss classical quality measures for synthesis plans, such as overall yield and convergency, and demonstrate that convergency has a built-in inconsistency which could render its use in synthesis planning questionable. Decalin is used as an illustrative example of the use and implications of our results.

Original languageEnglish
Article number19
JournalJournal of Cheminformatics
Volume10
Number of pages21
ISSN1758-2946
DOIs
Publication statusPublished - 5. Apr 2018

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Keywords

  • Algorithm
  • Bond set
  • Convergency
  • Decalin
  • Hypergraph
  • Hyperpath
  • Synthesis planning

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