Lipase‐Catalyzed Kinetic Resolution of Novel Antifungal N‐Substituted Benzimidazole Derivatives. Issue 4 (29th February 2016)

• Record Type: Journal Article
• Authors: Łukowska‐Chojnacka, Edyta; Staniszewska, Monika; Bondaryk, Małgorzata; Maurin, Jan K.; Bretner, Maria
• Is Part Of: Chirality. Volume 28:Issue 4(2016)
• Page Start: 347
• Page End: 354
• Publication Date: 2016-02-29
• Subjects: azole -- benzimidazole -- enzyme -- lipase -- enzymatic transesterification -- kinetic resolution -- antifungal activity; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22591
• Languages: English
• ISSNs: 0899-0042

Abstract

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, andacetylation 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 atransesterification reaction was applied and the influence of a lipase type and solvent on theenantioselectivity 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. Abstract : A series of new N ‐substituted benzimidazole derivatives with high antifungal activity against Candida albicans 900028 ATCC was synthesized. Racemic mixtures of alcohols were separated in lipase‐catalyzed transesterification. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E>100).