Synthesis of Small 1,2,3-Triazoles for Antimicrobial Evaluation

Abstract

Antibiotic resistance is an increasing problem globally. Overuse exposes bacteria to different kinds of antibiotics, to which they in time become resistant to. It is therefore important to develop novel antimicrobial structures to combat this threat. Libraries of structures based on antimicrobial peptide mimics isolated from the Barents sea have previously been prepared with different scaffold structures. In general, the structures consist of an aromatic group connected through a linker/scaffold to a cationic N-group. This Thesis is a continuation of this work, and the main objective has been the synthesis of small 1,4-disubstituted 1,2,3-triazoles for antimicrobial screening. The synthesis routes in this Thesis are outlined in Scheme 1. The triazoles 3a-d were prepared utilizing a copper-catalyzed click reaction to form triazoles from azides. The triazoles were refluxed in ethylene diamine to form the amines 4a-d, which were further reacted to form the desired ammonium salts 4a*-d* and guanedyl salts 5a and 5b. A total of six compounds were prepared, and two ammonium salts (4a* and 4b*) and one guanedyl salt (5b), were tested and found pure enough for antimicrobial screening. The purity was analyzed by HPLC, with a purity threshold of 95% for antimicrobial screening. The ammonium salts 4a* and 4b* both had a purity of > 99%, and 5b had a purity of 99%.