Biotransformation of digitoxigenin by Cochliobolus lunatus

Abstract

A reação de biotransformação da digitoxigenina (1) por Cochliobolus lunatus foi investigada. Foram realizados experimentos com duração de 4 dias, que resultaram no isolamento de quatro produtos, cujas estruturas químicas foram elucidadas como sendo 1β-hidroxidigitoxigenina (2), 7β-hidroxidigitoxigenina (3), 8β-hidroxidigitoxigenina (4) e digitoxigenona (5). A obtenção desses produtos nas condições empregadas nunca foi anteriormente descrita. A produção da substância 4 em uma reação de biotransformação também é inédita.The biotransformation of digitoxigenin (1) by Cochliobolus lunatus was investigated. The biotransformation reaction was carried out in a 4-day process, resulting in the isolation of four products, whose structures were elucidated as 1β-hydroxydigitoxigenin (2), 7β-hydroxydigitoxigenin (3), 8β-hydroxydigitoxigenin (4) and digitoxigenone (5). The production of these derivatives under the employed conditions has never been described so far. This is also the first report on the production of compound 4 by a biotransformation reaction.Keywords: digitoxigenin, Cochliobolus lunatus, 1β-hydroxydigitoxigenin, 7β-hydroxydigitoxigenin, 8β-hydroxydigitoxigenin, digitoxigenone IntroductionEnzymes are known to possess a wide substrate tolerance by keeping their exquisite catalytic properties with respect to chemo-, regio-and enantio-selectivity, playing an important role in biotransformations. 1 Biotransformation reactions can be accomplished at room temperature and in aqueous medium, presenting itself as a milder alternative to classical chemical reactions, 2-4 being employed for the resolution of racemates and to introduce chiral centers in substrates, among other uses. 5 Fungi are eukaryotic organisms that possess enzyme systems similar to those of mammalians. They usually present highly flexible metabolism, thus accepting varied sources of carbon and nitrogen. The ecological relations of these organisms include the metabolism of different secondary compounds, a feature sustained by diversified enzymatic systems, both intra and extra cellular, capable of carrying out numerous reactions. 6-8 Such attributes suggest fungi as suitable organisms to perform biotransformation reactions.The biotransformation of steroidal compounds by fungi has been extensively evaluated, including reactions with cardiac glycosides (Pádua et al. 9 and references herein; Table 3 of the present work). Digoxin, a Digitalis cardenolide, is still the drug of choice for the treatment of congestive heart failure, acting as a selective inhibitor of the Na + ,K + ATPase enzyme. Biotransformation of cardenolides has been investigated either as a strategy to obtain new derivatives or to convert the A-type cardenolides into the corresponding C-type compounds, which have clinical relevance. 9 The main reactions obtained so far for cardenolide biotransformation were hydroxylation in different positions of the steroidal skeleton, oxidation, glycosylation, epimerization and esterification of the hydroxyl group at C-3 (see Table 3 for references). An...

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Bioactive compounds of Curvularia species as a source of various biological activities and biotechnological applications

“…Curvularia lunata has been used as a tool to understand the effects of pH and glucose concentration on the production of rifamycin oxidase in a batch reactor (Banerjee and Srivastava, 1993 ). Pádua et al ( 2007 ) reported that Cochliobolus lunatus mediated biotransformation of digitoxigenin produces 1β-hydroxydigitoxigenin, 7β-hydroxydigitoxigenin, 8β-hydroxydigitoxigenin, and digitoxigenone as transformation products. Rifamycin B which is a clinically less active anti-biotic is transformed into Rifamycin S which is more potent and active by using rifamycine oxidase derived from Curvularia lunata which has a great commercial significance (Jobanputra et al, 2003 ).…”

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