Enantioselective HPLC combined with spectroscopic methods: a valid strategy to determine the absolute configuration of potential beta-secretase inhibitors.
A direct HPLC enantioseparation of three representative compounds of a new family of potential non-peptide beta-secretase inhibitors was performed on the immobilized Chiralpak IA chiral stationary phase. Semipreparative amounts of enantiopure forms were collected and submitted to stereochemical characterization. The absolute configuration was assigned by a multi-step methodology based on the combination of Mosher's method with circular dichroism (CD) spectroscopy. The results from the NMR/CD study fully correlated the configurational assignment obtained by a second approach involving single crystal X-ray diffraction.
Cirilli
Roberto
R
Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. rcirilli@iss.it
Ferretti
Rosella
R
La Regina
Giuseppe
G
Morelli
Gianluigi
G
Pierini
Marco
M
Piscitelli
Francesco
F
Silvestri
Romano
R
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002942:Circular Dichroism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases