Stereoselective synthesis of β-substituted- l-threonines from enantiopure 5-acetyl-2-isoxazolines

Abstract

Enantiomerically pure, 3-methyl- or 3-ethoxycarbonyl-substituted (5 S)- and (5 R)-5-acetyl-2-isoxazolines were obtained from the corresponding racemic mixtures by means of an enzymatic reduction with baker’s yeast, followed by the separation of the enantiopure syn- and anti-alcohols and oxidation of the alcohol group. The reaction between these ketones and (2 R)- Schöllkopf’s bislactim ether azaenolate was studied: using (5 S)- and (5 R)-3-methyl derivatives, two diastereoisomeric adducts were obtained in good yield and stereoselectivity, whereas reaction with the (5 S)- and (5 R)-3-ethoxycarbonyl derivatives led to a complex mixture of products. Subsequent controlled hydrolysis of the pyrazine ring led to β-(3-methyl-4,5-dihydro-isoxazol-5-yl)- l-threonines methyl ester together with the corresponding ( R)-valine dipeptides.