Lipase-Catalyzed Kinetic Resolution of Novel Antifungal N-Substituted Benzimidazole Derivatives

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• 作者：Edyta Łukowska-Chojnacka ; Monika Staniszewska ; Małgorzata Bondaryk ; Jan K. Maurin and Maria Bretner
• 关键词：azole ; benzimidazole ; enzyme ; lipase ; enzymatic transesterification ; kinetic resolution ; antifungal activity
• 刊名：Chirality
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：28
• 期：4
• 页码：347-354
• 全文大小：259K
• ISSN：1520-636X

文摘

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, pan class="TH_term4">reduction of ketonespan> to the racemic alcohols, and pan class="TH_term4">acetylation of alcoholspan> 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 pan class="TH_term4">transesterificationpan> reaction was applied and the influence of a lipase type and solvent on the pan class="TH_term4">enantioselectivitypan> 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.