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Determination of the absolute configuration of aromatase and dual aromatase‐sulfatase inhibitors by vibrational and electronic circular dichroism spectra analysis
Author(s) -
Abbate Sergio,
Longhi Giovanna,
Castiglioni Ettore,
Lebon France,
Wood Paul M.,
Woo Lawrence W. L.,
Potter Barry V. L.
Publication year - 2009
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20685
Subject(s) - chemistry , absolute configuration , vibrational circular dichroism , enantiomer , circular dichroism , conformational isomerism , aromatase , density functional theory , optical rotation , stereochemistry , computational chemistry , crystallography , organic chemistry , molecule , medicine , cancer , breast cancer
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. Chirality 2009. © 2009 Wiley‐Liss, Inc.