Chemistry of 4-fluoroglutamic acid. Part 4. Resolution of the racemic erythro and threo forms through their diastereomeric salts

Racemic erythro-(2S, 4R; 2R, 4S)-4-fluoroglutamic acid was successfully resolved, without derivatization, by combination with cinchonine under formation of a sparingly soluble salt with the (2S, 4R) enantiomer. The more soluble salt of the (2R, 4S) antipode, isolated from the mother liquors was further purified to reach sufficient optical purity. The threo-(2S,4S; 2R, 4R,)-4-fluoroglutamic acid could not be resolved underivatized, however, the resolution of its N-acetyl derivative with quinine proceeded smoothly to give the insoluble salt of the (2S, 4S) acid. Decomposition of the pure salts by acid and (in the case of the threo compound) hydrolytic removal of the N-acetyl group, furnished the desired 4-fluoroglutamic acid enantiomers with 99–100% optical purity.