Resolution of Tryptophan Ethyl Ester by Forming Diastereomeric Salts With Di-p-Toluoyl-L-Tartaric Acid

Abstract

A resolution of racemic tryptophan ethyl ester (TrpEt) was performed using L-di-p-toluoyl tartaric acid (L-DTTA) as the resolving agent. Response surface methodology (RSM) was employed to systematically investigate the effects of solvent dosage, molar ratio of racemate to resolving agent, and filtration temperature on the resolution efficiency. Under the optimized conditions, the less soluble diastereomeric salt L-TrpEt·L-DTTA was obtained with an optical purity of 92.4% and a yield of 89.1% after a single resolution step. The experimental results were in good agreement with the predicted values from RSM. To elucidate the chiral recognition mechanism during the resolution process, computational method combining Gaussian and Multiwfn 3.8 and VMD 1.9.3 was used to compare the intermolecular interactions of the less soluble salt L-TrpEt·L-DTTA to those of the more soluble salt D-TrpEt·L-DTTA. The results revealed that the intermolecular interactions in the former were stronger than those in the latter, indicating that L-DTTA preferentially recognizes L-TrpEt and forms the less soluble salt during the resolution process.