Enantiomeric 4-Acylamino-6-alkyloxy-2 Alkylthiopyrimidines As Potential A3 Adenosine Receptor Antagonists: HPLC Chiral Resolution and Absolute Configuration Assignment by a Full Set of Chiroptical Spectroscopy
Academic Article
Publication Date:
2016
Abstract:
The chiral separation of enantiomeric couples of three potential A3 adenosine receptor
antagonists: (R/S)-N-(6-(1-phenylethoxy)-2-(propylthio)pyrimidin-4-yl)acetamide (1), (R/
S)-N-(2-(1-phenylethylthio)-6-propoxypyrimidin-4-yl)acetamide (2), and (R/S)-N-(2-(benzylthio)-
6-sec-butoxypyrimidin-4-yl)acetamide (3) was achieved by high-performance liquid chromatography
(HPLC). Three types of chiroptical spectroscopies, namely, optical rotatory dispersion
(ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD), were applied
to enantiomeric compounds. Through comparison with Density Functional Theory (DFT)
calculations, encompassing extensive conformational analysis, full assignment of the absolute
configuration (AC) for the three sets of compounds was obtained.
antagonists: (R/S)-N-(6-(1-phenylethoxy)-2-(propylthio)pyrimidin-4-yl)acetamide (1), (R/
S)-N-(2-(1-phenylethylthio)-6-propoxypyrimidin-4-yl)acetamide (2), and (R/S)-N-(2-(benzylthio)-
6-sec-butoxypyrimidin-4-yl)acetamide (3) was achieved by high-performance liquid chromatography
(HPLC). Three types of chiroptical spectroscopies, namely, optical rotatory dispersion
(ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD), were applied
to enantiomeric compounds. Through comparison with Density Functional Theory (DFT)
calculations, encompassing extensive conformational analysis, full assignment of the absolute
configuration (AC) for the three sets of compounds was obtained.
CRIS type:
1.1 Articolo in rivista
Keywords:
A3 adenosine receptor antagonists; absolute configuration assignment; chiral HPLC; Density Functional Theory (DFT); electronic circular dichroism (ECD); optical rotatory dispersion (ORD); vibrational circular dichroism (VCD); Analytical Chemistry; Catalysis; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Spectroscopy; Organic Chemistry
List of contributors:
Rossi, Daniela; Nasti, Rita; Marra, Annamaria; Meneghini, Silvia; Mazzeo, Giuseppe; Longhi, Giovanna; Memo, Maurizio; Cosimelli, Barbara; Greco, Giovanni; Novellino, Ettore; Da Settimo, Federico; Martini, Claudia; Taliani, Sabrina; Abbate, Sergio; Collina, Simona
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