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Abstract:
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In this study, a series of chalcones (15a#j) and (1E,4E)-1,5-diphenyl-1,4-pentadien-3-one (16) were synthesized by base catalyzed aldol condensation. These compounds were used as substrates in biotransformation reactions mediated by Saccharomyces cerevisiae (baker#s yeast, BY, and industrial strains CAT-1 and PE-2) and Candida glabrata yeasts, in organic media or in biphasic systems. The á,â-unsaturated carbonyl compounds were obtained with good yield (50-94%) and were fully characterized by 1H NMR and IR spectroscopy and melting point. The compounds were reduced with NaBH4 to obtain racemic alcohols, used as standards in chromatography analysis. The biotransformation of these compounds, catalyzed by yeasts, was chemoselective, and formed only the corresponding saturated ketones. Using S. cerevisiae in the bio-hydrogenation of the chalcone 15a, several reaction parameters were evaluated: biocatalytic system, yeast concentration, shaking rate, temperature, pH, substrate concentration, organic solvent and volume of aqueous and organic phases. The influence of substituent groups on rings A and B of chalcones 15a-i was also considered. The highest values for percent conversion to product (19a) were obtained in the reactions mediated by S. cerevisiae yeast in biphasic systems, with magnetic stirring, at 30-45 °C and pH above 5.5. The cellular and substrate concentrations strongly influenced the conversion rates. The organic solvents with log P>3.2 (hexane, heptane) were the most appropriate, and an increase in the aqueous phase was important to retain the enzymes catalytically active. Using the C. glabrata yeast, the best conditions for the reduction of chalcone 15a were 25 °C, pH 5.5, and cellular concentration of 16.7 gL-1, and the most efficient protection and/or the immobilization was obtained using the biphasic system. The influence of substituents on rings A and B of chalcones 15a-i was, in general, low and no correlation between the donor and withdrawing electrons groups was observed. Using the same experimental conditions, the four yeasts formed the dehydrochalcone 19a in a chemoselective process in 24 h of reactions (~50%). Thus, the S. cerevisiae and C. glabrata yeasts presented a great potential to be used as biocatalysts in the hydrogenation of activated carbon-carbon double bonds. The biotransformation product of 1E,4E)-1,5-diphenyl-1,4-pentadien-3-one mediated by BY was also dependent on the catalytic system. In a biphasic system, the major product obtained was 1,5-diphenyl-3-pentanone (23) after 24 h (>99%). With addition of trehalose or sucrose to the reaction medium, two products were obtained, these being (1E)-1,5-diphenyl-1-penten-3-one (22) and 23. In conclusion, the use of microorganisms as biocatalysts in the biotransformation of á,â-unsaturated carbonyl compounds is a viable alternative to obtain saturated ketones, with mild reaction conditions, low cost reagents and low environmental pollution |
