A rapid and simple method for the resolution of Z-γ,γ1-di-tert-butyl-D,L-carboxyglutamic acid methyl ester is described. The new procedure is based on the enzymatic enantioselective saponification of the methyl ester by the endoprotease papain. Using a simple HPLC protocol the enantiomeric excess of Z-di-tert-butyl-L-Gla-OH has been shown to be higher than 99.5%. The procedures described in this communication allow the resolution, analysis, and downstream process of multi-gram amounts of the Gla derivative in 48 h.
|Publication status||Published - 15 Jan 1996|