Chiral separation of nipecotic acid amides.
1-Decyl-3-(N,N-diethylcarbamoyl)piperidine (1) and alpha,alpha'-bis[3-(N-benzyl-N-methylcarbamoyl)piperidinol]-p-xyle ne (2) represent mono-N-substituted and bis-N-substituted carbamoylpiperidines, or nipecotic acid amides, respectively. Initially, several attempts were made to resolve these compounds using beta-cyclodextrin, cellulose carbamate and Pirkle-type columns. However, the interactions of the stereoisomers of the two compounds with these stationary phases did not differ enough to permit satisfactory separations. Baseline resolution was achieved using an alpha 1-acid glycoprotein (AGP) chiral column. The mobile phase was phosphate buffer (pH 7.0). Tetrabutylammonium (TBA) was used as the cationic modifier and ethanol as the uncharged modifier. Circular dichroism was used to identify the enantiomers. Compound 1 was resolved into positive and negative enantiomers and 2 into positive and negative enantiomers and a meso diastereomer. The influence of pH, buffer ionic strength, cationic and uncharged modifier concentrations on retention, chiral selectivity and resolution were evaluated. Based on the results, it is suggested that both ionic and hydrophobic interactions may be responsible for retention and resolution.
Feng
Z
Z
Department of Medicinal Chemistry, University of Tennessee, Memphis 38163.
Gollamudi
R
R
Han
G
G
Tang
Y
Y
Armstrong
D W
DW
D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002942:Circular Dichroism; D005343:Fibrinolytic Agents / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D009557:Nipecotic Acids / Q000302:isolation & purification*; D009961:Orosomucoid; D000644:Quaternary Ammonium Compounds; D013237:Stereoisomerism
D002021:Buffers; D005343:Fibrinolytic Agents; D009557:Nipecotic Acids; D009961:Orosomucoid; D000644:Quaternary Ammonium Compounds; C077875:alpha,alpha'-bis(3-(N-benzyl-N-methylcarbamoyl)piperidinol)-4-xylene; C077874:1-decyl-3-(N,N-diethylcarbamoyl)piperidine; C009405:tetrabutylammonium