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

摘要

Diisopropyl #alpha#-chloroacetoxyphosphonates derived from propanal, isobutanal, 3-methylmercaptopropanal, 3-methylbutanal and (S)-2-methylbutanal were resolved by enzyme-catalysed hydrolysis. Lipases preferentially hydrolysed the (S)-asters 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)-#alpha#-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-#alpha#-aminobutyric acid. Their enantiomeric purity was determined by HPLC on a chiral stationary phase after derivatisation at nitrogen.