Enzymatic resolution of substituted 2-methyl-propionic acid
AssigneeGenencor International, Inc.
InventorsMatthew W. Chase, Charles T. Goodhue, Robert Seemayer, Gregory M. Whited
Life of this patent
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Abstract
Provided are enzymatic methods for the selective hydrolytic resolution of certain enantiomers of a pharmaceutical compound, the pharmaceutical compound comprising a (.+-.) mixture of a .alpha.-substituted 2-methyl proprionic acid derivative. Specifically provided is the selective enzymatic resolution of either the R(+) or S(-) enantiomer of (.+-.)-ethyl ciprofibrate. Also provided are substantially pure enantiomers of R(+) and S(-) ciprofibrate.
Claims14
A process for the enzymatic resolution of one or more enantiomers of a proprionic acid derivative of the formula:
- ##STR5## wherein:
- R and R.sup.1 defined individually are substituted or unsubstituted alkyl of C1-C4 (where the alkyl group can be substituted with halogen, sulfur or nitrile) or R and R.sup.1 taken together with the asymmetric center of the compound of Formula I form a substituted or unsubstituted cyclic ring structure of C3-C6 (wherein the ring structure may be substituted with alkyl of C1-C6, halogen or aryl);
- provided, however, that either R or R.sup.1 is larger than the other by at least one carbon atom or equivalent bond length;
- n=0-6;
- R.sup.2 is O or CH.sub.2 provided that R.sup.2 can be on either side of the (CH.sub.2).sub.n chain;
- and
- R.sup.3 is H, NHR.sup.4 (where R.sup.4 is H, alkyl or an amino acid), alkyl of 1-6 carbon atoms or substituted alkyl of 1-6 carbon atoms (where the substitutent is selected from the group consisting of halogen and CN);
- the process comprising reacting the proprionic acid derivative with an esterhydrolase or protease to selectively resolve the substantially pure R or S enantiomer under conditions suitable for such resolution.
Dependencies are inferred from the claim text.