The synthesis of the two enantiomers of 1-(3-bromo-5-isoxazolyl)-2-(tert-butylamino)ethanol (1), a potent and selective β2-adrenergic stimulant, has been efficiently accomplished by enzyme-catalyzed transformations. The absolute configurations are attributed to (+)- and (-)-1 by correlation with (S)-3-butyn-2-ol. The S enantiomer was prepared in >98% enantiomeric excess by reducing α-bromo ketone 4 in the presence of alcohol dehydrogenase from Thermoanaerobium brockii and the R enantiomer was obtained in 97% ee through a kinetic resolution of the racemic bromohydrin (±)-5, in organic solvents, catalyzed by lipase P from Pseudomonas fluorescens. The experimental conditions for the lipase-catalyzed asymmetric transesterifications were optimized in order to improve reaction rates and the enantiomeric excess of the products.

CHEMOENZYMATIC SYNTHESIS OF CHIRAL ISOXAZOLE DERIVATIVES / M. De Amici, C. De Micheli, G. Carrea, S. Spezia. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - 54:11(1989), pp. 2646-2650.

CHEMOENZYMATIC SYNTHESIS OF CHIRAL ISOXAZOLE DERIVATIVES

M. De Amici
Primo
;
C. De Micheli
Secondo
;
1989

Abstract

The synthesis of the two enantiomers of 1-(3-bromo-5-isoxazolyl)-2-(tert-butylamino)ethanol (1), a potent and selective β2-adrenergic stimulant, has been efficiently accomplished by enzyme-catalyzed transformations. The absolute configurations are attributed to (+)- and (-)-1 by correlation with (S)-3-butyn-2-ol. The S enantiomer was prepared in >98% enantiomeric excess by reducing α-bromo ketone 4 in the presence of alcohol dehydrogenase from Thermoanaerobium brockii and the R enantiomer was obtained in 97% ee through a kinetic resolution of the racemic bromohydrin (±)-5, in organic solvents, catalyzed by lipase P from Pseudomonas fluorescens. The experimental conditions for the lipase-catalyzed asymmetric transesterifications were optimized in order to improve reaction rates and the enantiomeric excess of the products.
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/184388
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