Synthesis of Amphiphilic Derivatives of Fusidane Triterpenoids
DOI:
https://doi.org/10.31489/2959-0663/3-26-7Keywords:
triterpenoids, fusidic acid, amphiphilic derivatives, tertiary amines, quaternization reaction, quaternary ammonium salts, reductive aminationAbstract
Fusidic acid exhibits bacteriostatic activity, transitioning to bactericidal at high doses, primarily against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. This underscores its high potential for functionalizing reactive centers with pharmacophore groups to develop semisynthetic analogs as promising antibiotics. In medicinal chemistry, studies on amphiphilic fusidic acid derivatives with enhanced bioavailability and biological activity are highly relevant. In this work, amphiphilic derivatives of the fusidic acid (FA) were synthesized via quaternization of tertiary amines and pyridines (triethylamine, pyridine, N, N-dimethylaminopyridine, N-methylpiperidine) by bromoethyl fusidate and 3-bromopropylamine methylfusidate. The carboxylic group of FA was brominated using 1,2-dibromoethane in dry acetone with K2CO3 under reflux. Reaction of the FA bromo- derivative with tertiary amines and pyridines in DMF at 70 °C afforded ammonium salts in 62–70 % yields. The FA bromoamine, obtained via reductive amination, was involved into the reaction with N-containing compounds in DMF upon heating to yield target products in 60–67 % yields. Structures of novel FA analogs were confirmed by NMR spectroscopy and mass-spectrometry. The obtained FA amphiphilic analogs hold potential for further development of antimicrobial agents.
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