Synthesis of Cationic Amphiphiles Based on L-Tartaric Acid Scaffolds for Antimicrobial Screening

Abstract

Infectious diseases are still one of the main causes of death nowadays. The development of new antibiotics it is still as necessary as it was when penicillin was first discovered in 1929. As bacteria grow resistant to commonly used antibiotics the need for new agents active against these new resistant strains is of remarkable importance. The goal of this Master s thesis was to synthesized new cationic amphiphiles from L-tartaric acid derivatives for biological testing against bacteria. The target amphiphiles were based on a simplified model from marine natural products with promising antibacterial activity. The target molecules are composed of two aromatic lyophilic groups, and of two hydrophilic groups containing at least one nitrogen. In order to obtain the cationic amphiphiles, at first two different alkylation procedures were performed for diisopropyl and dimethyl L-tartrate with benzyl bromides, to introduce the lyophilic groups to the molecule. The obtained O-benzylated L-tartrates were treated with ethylenediamine for the obtention of the nitrogen containing hydrophilic group. Since the amidation was faster for methyl esters, an alternative for the amidation of diisopropyl O-benzylated L-tartrates was studied. Via basic hydrolysis and esterification with an acid catalyst, a series of dimethyl esters was obtained. Finally, the O-benzylated diamines were treated with HCl in MeCN to obtain the corresponding salts (target cationic amphiphiles). The purity of the salts was assessed by HPLC experiments to evaluate if they comply with the minimum 95% required for biological testing.