Enzymes in organic chemistry. Part 9: Chemo-enzymatic synthesis of phosphonic acid analogues of l-valine, l-leucine, l-isoleucine, l-methionine and l-α-aminobutyric acid of high enantiomeric excess

Abstract

Diisopropyl α-chloroacetoxyphosphonates derived from propanal, isobutanal, 3-methylmercaptopropanal, 3-methylbutanal and ( S)-2-methylbutanal were resolved by enzyme-catalysed hydrolysis. Lipases preferentially hydrolysed the ( S)-esters and protease Chirazyme ® P-2 the ( R)-esters. Replacing the isopropyl groups by t-butyl groups reduced the reaction rate; replacing them by a 2,2-dimethylpropane-1,3-diyl group increased the reaction rate. ( S)-α-Hydroxyphosphonates (ee 92–99%), obtained with the protease except one, were transformed into phosphonic acid analogues of l-valine, l-leucine, l-isoleucine, l-methionine and l-α-aminobutyric acid. Their enantiomeric purity was determined by HPLC on a chiral stationary phase after derivatisation at nitrogen.