Lipase‐Catalyzed Kinetic Resolution of Novel Antifungal N‐Substituted Benzimidazole Derivatives |
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| Authors: | Edyta Łukowska‐Chojnacka Monika Staniszewska Małgorzata Bondaryk Jan K. Maurin Maria Bretner |
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| Affiliation: | 1. Faculty of Chemistry, Institute of Biotechnology, Warsaw University of Technology, Warsaw, Poland;2. Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health‐National Institute of Hygiene, Warsaw, Poland;3. National Centre for Nuclear Research, Otwock, Poland;4. National Medicines Institute, Warsaw, Poland |
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| Abstract: | A series of new N‐substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase‐catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100). Chirality 28:347–354, 2016. © 2016 Wiley Periodicals, Inc. |
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| Keywords: | azole benzimidazole enzyme lipase enzymatic transesterification kinetic resolution antifungal activity |
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