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

Organics. 2023. Vol. 4. No. 2. P. 186–195.

Гадомский С. Я., Третьяков Б. А., Terentiev A.

We describe a novel two-step approach 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 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 by hydroxylamine. For
both stages, universal synthetic methods are developed to exclude additional purification procedures
for the target compounds. Sixteen hydroxamic acids are synthesized using the developed approach.
Most of the compounds are obtained for the first time.

Keywords: N-substituted succinimides, hydroxylamine, hydroxamic acids, imide ring opening, HDAC inhibitors, MMP inhibitors, N-замещенные сукцинимиды, гидроксиламин, гидроксамовые кислоты, раскрытие имидного цикла, ингибиторы HDAC