CONICET | Buscador de Institutos y Recursos Humanos

Drug enantiomers many times differ in pharmacological effects, potency, or toxicity. One example of the different pharmacological response of two enantiomers is propanolol whose S enantiomer possesses antihypertensive and antiarrythmic activities while the R-enantiomer acts as a contraceptive. Biocatalysis has become an increasingly valuable tool for the easy preparation of chiral compounds, having great potential because of their sustainable methodology for the production of chemicals, that is, green chemistry. Although the potential of fungi as biocatalysts has been demonstrated in some previous works,new studies exploring the potentiality of fungal species as new routes to obtain chiral compounds are highly welcome. In this work, the fungal biotransformation of 4-(4´-hidroxyphenyl)-3-buten-2-one(1) is reported along with the evaluation of the antifungal activity of the chiral products. In addition, the racemic mixture of the product was tested too. The C-C double bond of 1 was hydrogenated and the C=O was enantioselectively reduced to alcohol by both fungal strains to afford 4-(4?-hidroxyphenyl) butan-2-ol. A. fumigatus has the ability of generate S-(+)-4-(4?-hidroxifenil) butan-2-ol (2a) with ee= 99% and T. cutaneum, R-(-)-4-(4?- hidroxifenil) butan-2-ol (2b) with ee= 99%. We have found that Af and Tc are efficient biocatalysts for the enantioselective C-C double bond and C=O reductions of 1 into 2a and 2b,respectively, leading to the introduction of one chiral center, with high enantioselectivity, into an achiral structure. Although the activity of the R-enantiomer (2a) against the yeasts is moderate (MIC 250 ug/mL), it is at least four times higher than the S-enantiomer (2b) and the racemic (2) (both MIC >1000 ug/mL). This work provides a new evidence that fungal biocatalysis is useful to prepare chiral compounds by an environmentally viable alternative, that could be new alternatives in the search of bioactive compounds.

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