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

Diisopropyl alpha-chloroacetoxyphosphonates derived from propanal, isobutan al, 3-methylmercaptopropanal, 3-methylbutanal and (S)-2-methylbutanal were resolved by enzyme-catalysed hydrolysis. Lipases preferentially hydrolysed the (S)-esters and protease Chirazyme(R) P-2 the (R)-esters. Replacing the isopropyl groups by t-butyl groups reduced the reaction rate; replacing the m by a 2,2-dimethylpropane- 1,3-diyl group increased the reaction rate. (S) -alpha-Hydroxyphosphonates (ee 92-99%), obtained with the protease except o ne, were transformed into phosphonic acid analogues of L-valine, L-leucine, L-isoleucine, L-methionine and L-alpha-aminobutyric acid. Their enantiomer ic purity was determined by HPLC on a chiral stationary phase after derivat isation at nitrogen. (C) 1999 Elsevier Science Ltd. All rights reserved.