A Reaction of N-substituted Succinimides with Hydroxylamine as a Novel Approach to the Synthesis of Hydroxamic Acids

Submitting author affiliation:
Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS, Chernogolovka, Russian Federation

Beilstein Arch. 2023, 20236. https://doi.org/10.3762/bxiv.2023.6.v1

Published 31 Jan 2023

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We describe a new reaction for the synthesis of compounds with a hydroxylamide group (hydroxamic acids) which are widely known for their biological activity (histone deacetylase inhibitors, matrix metalloproteinases inhibitors and others). The reaction involves the interaction between N-substituted succinimides and hydroxylamine in aqueous solution. A novel two step approach to the synthesis of hydroxamic acids was developed based on the new reaction. The first stage is the synthesis of N-substituted succinimide via the reaction of aromatic amine or carboxylic acid hydrazide with succinic anhydride. The second step involves the imide ring opening reaction in the presence of hydroxylamine. For the both stages, universal synthetic methods have been developed that exclude additional purification stages for the target compounds. Sixteen hydroxamic acids were synthesized using the developed approach. Most of the compounds were obtained for the first time.

Keywords: N-substituted succinimides; hydroxylamine; hydroxamic acids; imide ring opening; HDAC inhibitors; MMP inhibitors

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Tretyakov, B.; Gadomsky, S.; Terentiev, A. Beilstein Arch. 2023, 20236. doi:10.3762/bxiv.2023.6.v1

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