Chemical discrimination of compounds possessing an amino group
Péter, M.ár.
Acta Pharmaceutica Hungarica 72(2): 137-149
2002
ISSN/ISBN: 0001-6659 PMID: 12498041 Document Number: 545025
Cyclic 1,3-amino alcohols have been successfully resolved via lipase-catalysed O-acylation of their Z derivatives, using vinyl butyrate as acyl donor in different ether solvents. A direct HPLC method was developed for the monitoring of the resolutions. Most of the screened lipases preferred the S enantiomer. Both alcohol and ester enantiomers were obtained in ee > 90% after gram-scale resolutions. A new isothiocyanato-type CDA, (1S,2S)- or (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propyl isothiocyanate [(R,R)- or (S,S)-DANI], was designed for the indirect HPLC enantioseparation of primary and secondary amino compounds. The new reagent can be readily synthetized in optically pure form (> or = 99.5%) after a straightforward two-step synthesis. It is stable chemically and stereochemically both in the solid and in the solution phase. It is available in both enantiomeric forms, allowing the appropriate selection of the elution sequence. The kinetics of derivatization was studied in detail for alpha-amino acids and for beta-blockers. The quantitativeness of reactions was ensured by optimization of reaction conditions (pH, reagent excess, temperature). As concerns the HPLC analyses of the thiourea derivatives formed, significant differences were found between selectivities of the organic modifiers applied; in most cases, MeOH proved much more effective than MeCN with respect to both retention times and resolutions. In conclusion, the new CDA was capable of the resolution of most of the investigated analytes.