Lossen Rearrangement of p-Toluenesulfonates of N-Oxyimides in Basic Condition, Theoretical Study, and Molecular Docking

Monika Kijewska; Abeer A Sharfalddin; Łukasz Jaremko; Marta Cal; Bartosz Setner; Miłosz Siczek; Piotr Stefanowicz; Mostafa A Hussien; Abdul-Hamid Emwas; Mariusz Jaremko

doi:10.3389/fchem.2021.662533

Lossen Rearrangement of p-Toluenesulfonates of N-Oxyimides in Basic Condition, Theoretical Study, and Molecular Docking

Front Chem. 2021 Apr 15:9:662533. doi: 10.3389/fchem.2021.662533. eCollection 2021.

Authors

Affiliations

¹ Faculty of Chemistry, University of Wrocław, Wrocław, Poland.
² Department of Chemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
³ Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Jeddah, Saudi Arabia.
⁴ Department of Chemistry Faculty of Science, Port Said University, Port Said, Egypt.
⁵ Core Labs, King Abdullah University of Science and Technology (KAUST), Jeddah, Saudi Arabia.

Abstract

The sulfonic esters of N-oxyimides are a group of compounds with a wide range of biological activities, as well as a unique reactivity toward amines. They undergo this reaction with primary amines and other nucleophilic reagents according to a Lossen-like rearrangement. The reaction is initiated by nucleophilic attack on a carbonyl group in the succinimide ring followed by isocyanate formation, which next interacts with another nucleophile molecule forming an addition product (e.g., ureido or urethane derivative). However, the secondary amines are also susceptible to other reactions leading to products containing the maleimide ring formed by sulphonic acid elimination. In the case of tertiary amines, this reaction is predominant. To explain the phenomenon of the reactivity of the N- oxyimides toward different types of amines, we employed various spectroscopic and X-ray approaches as well as DFT calculation. Results suggest that the basicity of the amine used for the reaction plays a crucial role in the reaction mechanism that eventually dominates the entire chemical process. Moreover, we applied molecular docking to investigate the ability of the products to act as serine protease inhibitors using human leukocyte elastase (HLE).

Keywords: DFT; N-oxyimides; NMR; XRD; molecular docking; p-toluenesulfonates.