In this paper, we compare the most popular Atom-to-Atom Mapping (AAM) tools: ChemAxon, [1] Indigo, [2] RDTool, [3] NameRXN (NextMove), [4] and RXNMapper [5] which implement different AAM algorithms. An open-source RDTool program was optimized, and its modified version ("new RDTool") was considered together with several consensus mapping strategies. The Condensed Graph of Reaction approach was used to calculate chemical distances and develop the "AAM fixer" algorithm for an automatized correction of erroneous mapping. The benchmarking calculations were performed on a Golden dataset containing 1851 manually mapped and curated reactions. The best performing RXNMapper program together with the AMM Fixer was applied to map the USPTO database. The Golden dataset, mapped USPTO and optimized RDTool are available in the GitHub repository https://github.com/Laboratoire-de-Chemoinformatique.

Finding synthesis routes for molecules of interest is essential in the discovery of new drugs and materials. To find such routes, computer-assisted synthesis planning (CASP) methods are employed, which rely on a single-step model of chemical reactivity. In this study, we introduce a template-based single-step retrosynthesis model based on Modern Hopfield Networks, which learn an encoding of both molecules and reaction templates in order to predict the relevance of templates for a given molecule. The template representation allows generalization across different reactions and significantly improves the performance of template relevance prediction, especially for templates with few or zero training examples. With inference speed up to orders of magnitude faster than baseline methods, we improve or match the state-of-the-art performance for top- k exact match accuracy for k ≥ 3 in the retrosynthesis benchmark USPTO-50k. Code to reproduce the results is available at .

The quality of experimental data for chemical reactions is a critical consideration for any reaction-driven study. However, the curation of reaction data has not been extensively discussed in the literature so far. Here, we suggest a 4 steps protocol that includes the curation of individual structures (reactants and products), chemical transformations, reaction conditions and endpoints. Its implementation in Python3 using CGRTools toolkit has been used to clean three popular reaction databases Reaxys, USPTO and Pistachio. The curated USPTO database is available in the GitHub repository (Laboratoire-de-Chemoinformatique/Reaction_Data_Cleaning).

The stereoselective preparation of a novel 4’-spirocyclopropyl nucleoside analogue has been described using a semi-benzilic Favorskii rearrangement of a 4’-(2-chloro-3-oxocyclobutyl)spirofuranose as a key step. We demonstrated that the latter chiral spirocyclic intermediates, readily obtained on multigram scale from chiral pool starting materials, are highly suitable precursors to obtain full stereoselectivity in the reduction-ring contraction sequence. The downstream nucleobase introduction via Vorbrüggen glycosylation successfully resulted in the formation of the corresponding novel 4’-spirocyclic nucleoside analogue in a stereospecific manner.