On the Absolute Stereochemistry of Tolterodine: A Circular Dichroism Study
Tolterodine (<b>1</b>) 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 <span style="font-variant: small-caps;">l</span>-tartra...
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| Main Authors: | , , , |
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| Format: | Book |
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MDPI AG,
2019-01-01T00:00:00Z.
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| Summary: | Tolterodine (<b>1</b>) 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 <span style="font-variant: small-caps;">l</span>-tartrate salt of the (<i>R</i>)-enantiomer. However, the existing literature does not offer an ultimate proof of a stereoselective mode of action of <b>1</b>. A second open stereochemical issue concerns the absolute configuration (AC) of <b>1</b>. Neither the original patents nor subsequent studies have established the AC of <b>1</b> in an unambiguous way, although the AC of the <span style="font-variant: small-caps;">l</span>-tartrate salt of <b>1</b> was assigned by X-ray diffractometry. Finally, neither electronic nor vibrational circular dichroism (ECD and VCD) spectra of <b>1</b> are reported so far. We performed a thorough ECD/VCD study of <b>1</b> 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 <b>1</b> in an independent way. |
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| Item Description: | 1424-8247 10.3390/ph12010021 |