On the Absolute Stereochemistry of Tolterodine: A Circular Dichroism Study
AbstractTolterodine (1) is a potent muscarinic receptor antagonist used in the treatment of overactive urinary bladder (OAB) syndrome. Tolterodine is chiral and it was patented, and is currently marketed, as the l-tartrate salt of the (R)-enantiomer. However, the existing literature does not offer an ultimate proof of a stereoselective mode of action of 1. A second open stereochemical issue concerns the absolute configuration (AC) of 1. Neither the original patents nor subsequent studies have established the AC of 1 in an unambiguous way, although the AC of the l-tartrate salt of 1 was assigned by X-ray diffractometry. Finally, neither electronic nor vibrational circular dichroism (ECD and VCD) spectra of 1 are reported so far. We performed a thorough ECD/VCD study of 1 in different solvents and at variable temperatures. Solvent and temperature dependence highlighted the existence of moderate flexibility which was confirmed by molecular modelling. ECD calculations with time-dependent density functional theory (TDDFT) accurately reproduced the experimental spectra and allowed us to confirm the AC of 1 in an independent way. View Full-Text
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Górecki, M.; Zullo, V.; Iuliano, A.; Pescitelli, G. On the Absolute Stereochemistry of Tolterodine: A Circular Dichroism Study. Pharmaceuticals 2019, 12, 21.
Górecki M, Zullo V, Iuliano A, Pescitelli G. On the Absolute Stereochemistry of Tolterodine: A Circular Dichroism Study. Pharmaceuticals. 2019; 12(1):21.Chicago/Turabian Style
Górecki, Marcin; Zullo, Valerio; Iuliano, Anna; Pescitelli, Gennaro. 2019. "On the Absolute Stereochemistry of Tolterodine: A Circular Dichroism Study." Pharmaceuticals 12, no. 1: 21.
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