Enzymatic resolution of (±)-5-phenyl-4,5-dihydroisoxazole-3-carboxylic acid ethyl ester and its transformations into polyfunctionalised amino acids and dipeptides

Abstract

Enantiomerically pure (5 R)-(−)-5-phenyl-4,5-dihydroisoxazole-3-carboxylic acid ethyl ester was obtained via enzymatic resolution of the corresponding racemic mixture using a lipase from hog pancreas (PPL). The following reduction of the ester group to the corresponding alcohol and the oxidation of the latter led to (5 R)-(−)-5-phenyl-4,5-dihydroisoxazole-3-carbaldehyde, and the reaction between this and Schöllkopf’s reagent, (2 R)-(+)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine, gave mixtures of adducts with a good syn/ anti ratio. The steric configurations of the major diastereoisomer were assigned on the basis of spectroscopic data and X-ray analysis. The subsequent controlled hydrolysis of the pyrazine ring led to β-(5-phenyl-4,5-dihydroisoxazol-3-yl)-serine methyl esters and the corresponding dipeptides with ( R)-valine. Finally, reductive cleavage of the 4,5-dihydroisoxazole ring under hydrolytic conditions made it possible to obtain the corresponding polyfunctionalised dipeptides.