Affiliation:
1. Institute of Organic Chemistry Justus Liebig University Giessen Heinrich-Buff-Ring 17 35392 Giessen Germany
2. Department of Pharmaceutical and Pharmacological Sciences University of Padova Padova Italy
3. Institute of Biochemistry Justus Liebig University Giessen Heinrich-Buff-Ring 17 35392 Giessen Germany
Abstract
AbstractIn previous works, we demonstrated that tertiary 3‐chloropiperidines are potent chemotherapeutics, alkylating the DNA through the formation of bicyclic aziridinium ions. Herein, we report the synthesis of novel secondary 3‐chloropiperidine analogues. The synthesis incorporates a new procedure to monochlorinate unsaturated primary amines utilizing N‐chlorosuccinimide, while carefully monitoring the temperature to prevent dichlorination. Furthermore, we successfully isolated highly strained bicyclic aziridines by treating the secondary 3‐chloropiperidines with a sufficient amount of base. We conclude this work with a DNA cleavage assay as a proof of principle, comparing our previously known substrates to the novel compounds. In this, the secondary 3‐chloropiperidine as well as the isolated bicyclic aziridine, proved to be more effective than their tertiary counterpart.