Meyring, Michael and Muehlbacher, Joerg and Messer, Kim and Kastner-Pustet, Nikola and Bringmann, Gerhard and Mannschreck, Albrecht and Blaschke, Gottfried (2002) In vitro biotransformation of (R)- and (S)-thalidomide: Application of circular dichroism spectroscopy to the stereochemical characterization of the hydroxylated metabolites. ANALYTICAL CHEMISTRY, 74 (15). pp. 3726-3735. ISSN 0003-2700
Full text not available from this repository.Abstract
Circular dichroism (CD) spectroscopy was successfully used for the stereochemical characterization of the hydroxylated metabolites formed during the in vitro biotransformation of (R)- and (S)-thalidomide. Incubation extracts of the individual enantiomers were analyzed by HPLC on an achiral stationary phase combined with CD detection. The CD data of the almost enantiopure eluates of the metabolites were compared with the CD spectra quantum chemically calculated for the respective structures. The results allowed us a reliable determination of the absolute stereostructure for all of the metabolites. The chiral center of thalidomide is unaffected by the stereoselective biotransformation process. (3'R,5'R)-trans-5'-hydroxythalidomide is the main metabolite of (R)-thalidomide, which epimerizes spontaneously to give the more stable (3'S,5'R)-cis isomer. On the contrary, (S)-thalidomide is preferentially metabolized by hydroxylation in the phthalimide moiety, resulting in the formation of (S)-5-hydroxythalidomide.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THALIDOMIDE TERATOGENESIS; LIQUID-CHROMATOGRAPHY; TNF-ALPHA; IN-VITRO; ELECTROPHORESIS; STEREOANALYSIS; CONFIGURATION; MECHANISM; ANALOGS; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Sep 2021 05:41 |
| Last Modified: | 07 Sep 2021 05:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39994 |
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