Journal article

Authors list: Georg, Mats; Laping, Lina Alexandra; Billo, Veronica; Gatto, Barbara; Friedhoff, Peter; Göttlich, Richard

Publication year: 2023

Journal: ChemistryOpen

Volume number: 13

Issue number: 6

ISSN: 2191-1363

Open access status: Gold

DOI Link: https://doi.org/10.1002/open.202300181

Publisher: Wiley

Abstract: 

In 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.

Harvard Citation style: Georg, M., Laping, L., Billo, V., Gatto, B., Friedhoff, P. and Göttlich, R. (2023) Secondary 3-Chloropiperidines: Powerful Alkylating Agents, ChemistryOpen, 13(6), Article e202300181. https://doi.org/10.1002/open.202300181

APA Citation style: Georg, M., Laping, L., Billo, V., Gatto, B., Friedhoff, P., & Göttlich, R. (2023). Secondary 3-Chloropiperidines: Powerful Alkylating Agents. ChemistryOpen. 13(6), Article e202300181. https://doi.org/10.1002/open.202300181