1. Introduction Owing to its peculiarities, fluorine has drawn an increasing attention in the design of new drugs. Among them, fluorinated profens have received particular consideration in reference to the biological activity as successful non-steroidal anti-inflammatory drugs (NSAIDs). In the present communication we report the development of an enantioselective HPLC method for the resolution of racemic 2-(6-fluorophenanthren-1-yl)propionic acid (1),1 and the determination of the absolute configuration (AC) of its enantiomers through electronic circular dichroism (ECD) and time-dependent density functional theory (TD-DFT) computations. 2. Results and Discussion The column (S,S)-Whelk-O®1 was efficient for the enantioresolution of profen 1. The single enantiomeric fractions were collected and analyzed for determining their enantiomeric excess and ECD spectra. The AC of the enantiomers of 1 was determined by means of ECD theoretical calculations on (S)-1.2 Molecular mechanics conformational analysis and DFT geometry optimization at the B3LYP/TZ2P level isolated the 4 most populated conformers (a, 53.04%; b, 25.70%; c, 19.81%; d, 1.45%). TD-DFT calculations were performed at the B3LYP/TZ2P level and the theoretical ECD spectrum was determined. The ECD spectrum of the second-eluted enantiomer was found to be in excellent agreement with theoretical calculations on (S)-1; therefore, the AC of the first- and second-eluted enantiomers were assessed as (2R)-1 and (2S)-1, respectively. 3. References [1] Ricci, G., and Ruzziconi, R., J. Org. Chem. 2005, 70, 611-623. [2] Autschbach, J., Chirality 2009, 21, E116-E152.

D. Tedesco, R. Zanasi, R. Ruzziconi, M. Pistolozzi, A. M. Di Pietra, C. Bertucci (2011). Stereochemistry of 2-(6-fluorophenanthren-1-yl)propionic acid unveiled by enantioselective HPLC, ECD spectroscopy, and TD-DFT calculations. TRIESTE.

Stereochemistry of 2-(6-fluorophenanthren-1-yl)propionic acid unveiled by enantioselective HPLC, ECD spectroscopy, and TD-DFT calculations

TEDESCO, DANIELE;PISTOLOZZI, MARCO;DI PIETRA, ANNA MARIA;BERTUCCI, CARLO
2011

Abstract

1. Introduction Owing to its peculiarities, fluorine has drawn an increasing attention in the design of new drugs. Among them, fluorinated profens have received particular consideration in reference to the biological activity as successful non-steroidal anti-inflammatory drugs (NSAIDs). In the present communication we report the development of an enantioselective HPLC method for the resolution of racemic 2-(6-fluorophenanthren-1-yl)propionic acid (1),1 and the determination of the absolute configuration (AC) of its enantiomers through electronic circular dichroism (ECD) and time-dependent density functional theory (TD-DFT) computations. 2. Results and Discussion The column (S,S)-Whelk-O®1 was efficient for the enantioresolution of profen 1. The single enantiomeric fractions were collected and analyzed for determining their enantiomeric excess and ECD spectra. The AC of the enantiomers of 1 was determined by means of ECD theoretical calculations on (S)-1.2 Molecular mechanics conformational analysis and DFT geometry optimization at the B3LYP/TZ2P level isolated the 4 most populated conformers (a, 53.04%; b, 25.70%; c, 19.81%; d, 1.45%). TD-DFT calculations were performed at the B3LYP/TZ2P level and the theoretical ECD spectrum was determined. The ECD spectrum of the second-eluted enantiomer was found to be in excellent agreement with theoretical calculations on (S)-1; therefore, the AC of the first- and second-eluted enantiomers were assessed as (2R)-1 and (2S)-1, respectively. 3. References [1] Ricci, G., and Ruzziconi, R., J. Org. Chem. 2005, 70, 611-623. [2] Autschbach, J., Chirality 2009, 21, E116-E152.
2011
5° Meeting NUOVE PROSPETTIVE IN CHIMICA FARMACEUTICA (NPCF5) - ABSTRACTS
29
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D. Tedesco, R. Zanasi, R. Ruzziconi, M. Pistolozzi, A. M. Di Pietra, C. Bertucci (2011). Stereochemistry of 2-(6-fluorophenanthren-1-yl)propionic acid unveiled by enantioselective HPLC, ECD spectroscopy, and TD-DFT calculations. TRIESTE.
D. Tedesco; R. Zanasi; R. Ruzziconi; M. Pistolozzi; A. M. Di Pietra; C. Bertucci
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/125532
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