Chromatographia

, Volume 44, Issue 9–10, pp 465–472 | Cite as

Synthesis of new stable aliphatic isothiocyanate-based chiral derivatizing agent and application to indirect separation of chiral amino and thiol compounds

  • O. P. Kleidernigg
  • W. Lindner
Originals

Summary

A new chiral derivatizing agent (CDA) (1S, 2S) N-[(2-isothiocyanato)-cyclohexyl)-pivalinoyl amide ((S,S)-PDITC) is described. The CDA is available from 1,2-diamino cyclohexane (DACH) via a straightforward synthesis in both the (R,R) and (S,S)-configuration and can serve as a highly selective, stable reagent for the indirect resolution of chiral primary and secondary amines, amino acids and thiol compounds. The resulting diastereomeric thioureas and dithiocarbamates can be separated by simple RP-HPLC as demonstrated with a number of pharmaceutically important examples of amines and amino alcohol-type drugs. The latter diastereomers are compared with the well-established GITC derivatized compounds. The separation factors (α) of the diastereomeric thioureas range between 1.03 and 2.08 and were usually higher than those of the GITC derivatives. The chemical stability of the PDITC derivatives is excellent due to the absence of hydrolyzable ester groups— considered an advantage compared to GITC derivatives.

Key Words

Column liquid chromatography Indirect separation Chiral derivatization Stable CDA 

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Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 1997

Authors and Affiliations

  • O. P. Kleidernigg
    • 1
  • W. Lindner
    • 1
    • 2
  1. 1.Institute of Pharmaceutical Chemistry Karl-Franzens University of GrazGrazAustria
  2. 2.Institute of Analytical ChemistryUniversity of ViennaViennaAustria

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