Synthesis, absolute configuration, antibacterial, and antifungal activities of novel benzofuryl β-amino alcohols

Abstract

A series of new benzofuryl α-azole ketones was synthesized and reduced by asymmetric transfer hydrogenation (ATH). Novel benzofuryl β-amino alcohols bearing an imidazolyl and triazolyl substituents were obtained with excellent enantioselectivity (96-99%). The absolute configuration (R) of the products was confirmed by means of electronic circular dichroism (ECD) spectroscopy supported by theoretical calculations. Selected benzofuryl α-azole ketones were also successfully asymmetrically bioreduced by fungi of Saccharomyces cerevisiae and Aureobasidium pullulans species. Racemic and chiral β-amino alcohols, as well as benzofuryl α-amino and α-bromo ketones were evaluated for their antibacterial and antifungal activities. From among the synthesized β-amino alcohols, the highest antimicrobial activity was found for (R)-1-(3,5-dimethylbenzofuran-2-yl)-2-(1H-imidazol-1-yl)ethan-1-ol against S. aureus ATCC 25923 (MIC = 64, MBC = 96 μg mL-1) and (R)-1-(3,5-dimethylbenzofuran-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-ol against yeasts ofM. furfurDSM6170 (MIC=MBC=64 μgmL-1). In turn, from among the tested ketones, 1-(benzofuran-2-yl)-2-bromoethanones (1-4) were found to be the most active againstM. furfur DSM6170 (MIC =MBC = 1.5 μgmL-1) (MIC-minimal inhibitory concentration, MBC-minimal biocidal concentration).