Generation of Chemical Transformations: Reaction Pathways Prediction and Synthesis Design

Nowak, Grażna; Fic, Grzegorz

doi:10.1002/9783527645121.ch15

Cited by 1 publication

(1 citation statement)

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“…Other approaches include choosing bonds based on the existence of substructures of the target molecule that are isomorphic to easily accessible or available molecules found in libraries [ 16 – 19 ]. An overview of programs for synthesis planning based on retrosynthesis can be found in [ 3 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Finding the K best synthesis plans

et al. 2018

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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.

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