Secondary 3-Chloropiperidines: Powerful Alkylating Agents.
alkylation
antitumor agents
aziridine
primary chloroamine
secondary 3-chloropiperidine
Journal
ChemistryOpen
ISSN: 2191-1363
Titre abrégé: ChemistryOpen
Pays: Germany
ID NLM: 101594811
Informations de publication
Date de publication:
13 Dec 2023
13 Dec 2023
Historique:
revised:
15
10
2023
received:
21
09
2023
medline:
13
12
2023
pubmed:
13
12
2023
entrez:
13
12
2023
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38088585
doi: 10.1002/open.202300181
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202300181Informations de copyright
© 2023 The Authors. ChemistryOpen published by Wiley-VCH GmbH.
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