Retrosynthetic Analysis Made Easy with BIOVIA Reaction Planner

Small molecule discovery is a multifaceted challenge that goes beyond identifying a novel molecule with a desired target product profile. In many cases, identifying a synthetic pathway can present a similar level of complexity. Retrosynthetic analysis is a method used by chemists in organic synthesis planning, breaking down a target molecule into simpler precursor structures. Each precursor structure is analyzed using the same method iteratively until readily available structures are identified.

Retrosynthetic analysis is a powerful method in the design of chemical syntheses, as it focuses on simplifying complex structures. In many cases, there are multiple possible routes to synthesize an organic compound. Retrosynthesis helps identify these different routes and allows for a logical and straightforward comparison of their advantages to facilitate synthesis.

RETROSYNTHETIC ANALYSIS ON 3DEXPERIENCE® PLATFORM

BIOVIA now offers retrosynthetic analysis as part of the BIOVIA Reaction Planner application on the 3DEXPERIENCE platform, helping chemists identify relevant synthesis routes to create new small therapeutics molecules and accelerate the selection of candidate molecules amenable to synthesis. BIOVIA Reaction Planner leverages database exploration technology and machine learning (with a neural network specifically trained for chemistry) to create a chemical graph. Medicinal chemists can then extract synthesis routes automatically from this graph. It offers a unique combination of features such as a state-of-the-art published algorithm, a reference learning dataset and higher computational performance in a simple to use application for every chemist, thus accelerating and facilitating the challenging work of designing chemical plans.

BIOVIA Reaction Planner is also a cloud-native application, integrated with other applications on the 3DEXPERIENCE platform, including BIOVIA Insight for Research, BIOVIA Scientific Search and Intelligence, BIOVIA Materials Management and BIOVIA Scientific Notebook. By combining the power of these applications for chemistry and small molecule therapeutics discovery, BIOVIA offers an end-to-end workflow starting from the virtual design of new drugs to the planning of their experimental synthesis.

A CLOSER LOOK AT BIOVIA REACTION PLANNER

BIOVIA Reaction Planner breaks down the target molecules in readily available reactants (either in store or purchasable) by leveraging two components:

• The first component searches for the molecule in a database of known chemical reactions built from the ORDerly datasets [1]. Each reaction in this database may include additional information such as solvents, agents, yields, temperature, and a reference to the patent documenting it.
• The second component uses a custom implementation of the LocalRetro algorithm [2] to infer reactions that lead to the synthesis of the target molecule. LocalRetro is a neural network that classifies the target molecule into reactions templates (learned from the USPTO-50k dataset [3]) and then applies these templates to get the reactants.

These two components are combined in an algorithm that starts from the target molecule and iteratively breaks down the molecules until the readily available structures available are identified or stopping conditions are met. The application verifies commercial availability in the ACD and SCD databases (BIOVIA proprietary). The algorithm first builds a reaction graph with all the reactions and molecules that are either found in the databases or inferred by the neural network, and then extracts the top synthesis routes that meet the user-defined criteria.

Watch the video to see BIOVIA Reaction Planner in action!

BENEFITS OF BIOVIA REACTION PLANNER

BIOVIA Reaction Planner facilitates retrosynthetic analysis for the medicinal chemists, by using database exploration and machine learning. It helps the user identify the best synthesis routes for a target molecule, improving the success rate of the downstream experimental work; therefore, saving time and costs for drug discovery teams while increasing R&D efficiency.

Compared to manual synthetic planning, BIOVIA Reaction Planner can divide the retrosynthetic analysis by 2-10 folds, depending on the complexity of the target molecules, saving dozens of hours in each drug discovery project. 

Interested to learn more about BIOVIA Reaction Planner?

Nota Bene: BIOVIA Reaction Planner protects users from planning the synthesis of substances (or using substances) recorded as chemical weapons according to the Schedule 1 of the Chemical Weapons Convention.

References

[1] Daniel S. Wigh, Joe Arrowsmith, Alexander Pomberger, Kobi C. Felton, Alexei A. Lapkin, ORDerly: Data Sets and Benchmarks for Chemical Reaction Data, J. Chem. Inf. Model. 2024, 64, 9, 3790–3798

[2] Chen S, Jung Y. Deep Retrosynthetic Reaction Prediction using Local Reactivity and Global Attention. JACS Au. 2021 Aug 5;1(10):1612-1620.

[3] Nadine Schneider, Nikolaus Stiefl, Gregory A. Landrum, What’s What: The (Nearly) Definitive Guide to Reaction Role Assignment, J. Chem. Inf. Model. 2016, 56, 12, 2336–2346

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