Related Experiment Video
Updated: Aug 5, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Click Chemistry Approach to Derivatisation of Fluconazole
Michał Janowski1, Oleg M Demchuk2, Sylwia Andrzejczuk3
1Doctoral School, Medical University of Lublin, Chodzki 7, 20-093 Lublin, Poland.
Abstract:
The emergence of antimicrobial resistance necessitates the development of structurally novel agents with improved biological profiles. In this study, a series of new derivatives of fluconazole were designed, synthesized, and evaluated for antifungal activity. The synthetic approach involved esterification of hydroxyl group of fluconazole with an azide-group-containing benzoyl chloride, followed by copper-catalyzed azide-alkyne cycloaddition (CuAAC). The optimized catalytic system was based on a copper(I) catalyst generated from copper(II) palmitate and ascorbic acid. The transformations of the azide-containing derivatives were then performed. The obtained compounds were tested against reference strains of clinically relevant Candida spp., including C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 14243, C. auris CDC B11903, C. tropicalis ATCC 1369, C. glabrata ATCC 15126, and C. lusitaniae ATCC 3449. Some of the obtained derivatives showed very low toxicity in the MTT-based cell viability assay while maintaining high antifungal activity against selected strains.
Related Concept Videos
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Carboxylic Acid Derivatives: Overview
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
Nucleophilic Aromatic Substitution of Aryldiazonium Salts: Aromatic SN1
In the Sandmeyer reaction, for example, the diazonio group is replaced by a chloro, bromo, or cyano...
