title: Enantiomeric Separation of Monosubstituted Tryptophan Derivatives and Metabolites by HPLC with a Cinchona Alkaloid-Based Zwitterionic Chiral Stationary Phase and Its Application to the Evaluation of the Optical Purity of Synthesized 6-Chloro-l-Tryptophan.
abstract: 6-Chlorotryptophan possesses unique bioactivity and can be used as a precursor for several bioactive compounds in medicinal chemistry. It was enantioselectively synthesized by condensing 6-chloroindole with racemic N-acetylserine, followed by enzymatic hydrolysis with l-aminoacylase (EC 3.5.1.14). The optical purity was examined by conducting high-performance liquid chromatography with a Cinchona alkaloid-based zwitterionic chiral stationary phase (CSP) [CHIRALPAK(®) ZWIX(+)], which bears a chiral trans-2-aminocyclohexanesulfonic acid moiety tagged at C-9 of the Cinchona alka-loid. The zwitterionic CSP enabled efficient enantiomeric separations of monosubstituted tryptophan derivatives 1-methyltryptophan, 5-methyltryptophan, 6-methyltryptophan, 5-methoxytryptophan, and 6-chlorotryptophan with a methanol/H2O (98/2) mobile phase containing formic acid (FA) and diethylamine (DEA) additives. The mobile phase contains 25-75 mM FA and 20-50 mM DEA, enabling good separation of the enantiomers of each tryptophan derivative (α > 1.25). Thus, the optical purity of the synthesized 6-chloro-l-tryptophan was easily determined (greater than 99.0%) using HPLC with the zwitterionic CSP.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Sugiura
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Furuta
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Iwasa
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Iizuka
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ichiba
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Onozato
authors.affiliation: Department of Synthetic Organic Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Hikawa
authors.affiliation: Department of Synthetic Organic Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi-shi, Chiba, Japan.
authors.forename: Yuusaku
authors.initials: Y
authors.lastname: Yokoyama
keywords: 6-chlorotryptophan; CHIRALPAK® ZWIX(+); enantiomer; high-performance liquid chromatography