Determination of the absolute configuration of aromatase and dual aromatase-sulfatase inhibitors by vibrational and electronic circular dichroism spectra analysis.
The absolute configuration of a newly designed, letrozole-based chiral aromatase inhibitor that could not be defined by crystallographic techniques has been determined by means of vibrational and electronic circular dichroism and by optical rotation measurements combined with density functional theory calculations on possible conformers. The same absolute configurational assignment can be applied to the individual enantiomeric sulfamate esters, which are derived from the corresponding enantiomers of the chirally separated parent phenols, based on the similarity of the ECD spectrum of the sulfamate derivative to that of its phenolic precursor. The two enantiomeric sulfamate esters studied here are the first examples of nonsteroidal dual aromatase-sulfatase inhibitor whose activities have been evaluated on optically resolved enantiomers.
Abbate
Sergio
S
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Brescia, Brescia, Italy. abbate@med.unibs.it
Longhi
Giovanna
G
Castiglioni
Ettore
E
Lebon
France
F
Wood
Paul M
PM
Woo
Lawrence W L
LW
Potter
Barry V L
BV
D047072:Aromatase Inhibitors / Q000737:chemistry*; D002942:Circular Dichroism; D004583:Electrons; D054879:Halogenation; D000077289:Letrozole; D008958:Models, Molecular; D008968:Molecular Conformation; D009570:Nitriles / Q000737:chemistry; D009904:Optical Rotation; D013237:Stereoisomerism; D013429:Sulfatases / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000737:chemistry; D014732:Vibration
D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; D013429:Sulfatases