Synthesis of epimers of L-cyclopentenylglycine using enzymatic resolution

Both epimers of the naturally occurring nonproteinogenic amino acid L-cyclopentenylglycine, (2S,1′S)- and (2S,1′R)-2-(cyclopent-2′-enyl)glycine, were obtained via a procedure involving condensation of 3-chlorocyclopentene with diethyl acetylaminomalonate, deethoxycarbonylation, chromatographic separation of the resulting two pairs of enantiomers, and enzymatic resolution of the racemates employing enantioselective hydrolysis of the ethyl ester group with α-chymotrypsin. The method was used for preparation of 13C-labeled compounds of interest for biosynthetic tracer experiments. Enantiomeric purity of the products was determined by chiral HPLC on a Crownpak CR(+) column. The biologically active (2S,1′R) isomer was obtained as a pure compound and characterized for the first time. The (2R,1′R) and (2R,1′S) isomers were obtained as N-acetyl ethyl ester derivatives. Chirality 12:665–669, 2000. © 2000 Wiley-Liss, Inc.