Zusammenfassung
Analytical CE and HPLC methods were developed for the chiral separation of halogen-substituted 3-phenyl-3-(2-pyridyl)propylamines 1-4 (1: 3-(4- fluorophenyl)-, 2: 3-(3,4-difluorophenyl)-, 3: 3-(4-chlorophenyl)-, 4: 3-(3,4-dichlorophenyl)-), 3-(4-fluorophenyl)-3-(2-thiazolyl) propylamine (5), and 3-(4-fluorophenyl)-3- (1-benzylimidazol-2-yl) propylamine (6), which are building blocks for the ...
Zusammenfassung
Analytical CE and HPLC methods were developed for the chiral separation of halogen-substituted 3-phenyl-3-(2-pyridyl)propylamines 1-4 (1: 3-(4- fluorophenyl)-, 2: 3-(3,4-difluorophenyl)-, 3: 3-(4-chlorophenyl)-, 4: 3-(3,4-dichlorophenyl)-), 3-(4-fluorophenyl)-3-(2-thiazolyl) propylamine (5), and 3-(4-fluorophenyl)-3- (1-benzylimidazol-2-yl) propylamine (6), which are building blocks for the preparation of very potent arpromidine-type histamine H-2 receptor agonists. All amines were enantioseparated by CE with resolutions of at least 1.8 using alpha-, beta-, or gamma -cyclodextrin (CD) as chiral selectors. With heparin as buffer additive for CE the optical antipodes of 1-4 and 6 were separated with resolutions greater than or equal to1.8. On RP-18 columns the separation of the (+)-(S)-acetylmandelic acid amides of racemic 2 (R = 0.9, alpha = 1.07) and the thioureas prepared by addition of 6 to 2,3,4, 6-tetra-O-acetyl-beta -D-glucopyranosyl isothiocyanate (R = 2.0, alpha = 1.20) was successful, whereas the diastereomeric ureas prepared from 3 and (+)-(S)-1-(1-naphthyl ethyl isocyanate could not be resolved. Separation of the diastereomeric isoindoles prepared from 1-5, o-phthaldialdehyde and 2,3,4,6-tetra-0-acetyl-1-thio-beta -D-glucopyranoside was achieved on a RP-18 phase (R greater than or equal to 0.4, a greater than or equal to 1.02). Direct separation of the enantiomers of 3 and 4 was achieved on a Cyclobond I column (R greater than or equal to 0.9, alpha 1.07). alpha- and beta -CD were also useful as mobile phase additives for HPLC (3 and 4: RP-18 column, beta -CD, R greater than or equal to 0.4, alpha greater than or equal to 1.03; 3: RP-18 column, (alpha -CD: R = 0.5, alpha =1.04). Chirality 13:285-293, 2001. (C) 2001 Wiley-Liss, Inc.
Altmetric