Chemoenzymatic Synthesis of Chiral Isoxazole Derivatives

Article abstract of DOI:10.1021/jo00272a037

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 >98percent enantiomeric excess by reducing α-bromo ketone 4 in the presence of alcohol dehydrogenase from Thermoanaerobium brockii and the R enantiomer was obtained in 97percent 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.