5104-49-4Relevant academic research and scientific papers
Biotransformation with whole microbial systems in a continuous flow reactor: Resolution of (RS)-flurbiprofen using Aspergillus oryzae by direct esterification with ethanol in organic solvent
Tamborini, Lucia,Romano, Diego,Pinto, Andrea,Contente, Martina,Iannuzzi, Maria C.,Conti, Paola,Molinari, Francesco
, p. 6090 - 6093 (2013)
Cell-bound lipases of dry mycelium of Aspergillus oryzae were used in organic solvent for the resolution of racemic flurbiprofen by direct esterification with ethanol in a flow-chemistry reactor. Under flow conditions a significant reduction of the reaction time and an increase of the enantioselectivity were achieved compared to the batch mode. Moreover, the process was implemented by adding an in-line purification step integrated with the racemization of the unreacted flurbiprofen directly into a polymer-supported resin.
Improvement of dissolution and suppository release characteristics of flurbiprofen by inclusion complexation with heptakis(2,6-di-O-methyl)-β-cyclodextrin
Uekama,Imai,Maeda,Irie,Hirayama,Otagiri
, p. 841 - 845 (1985)
The inclusion behavior of methylated β-cyclodextrins, heptakis(2,6-di-O-methyl)-β-cyclodextrin (2), and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (3) in solution and the solid state was compared with that of natural β-cyclodextrin (1) using an anti-inflammatory drug, flurbiprofen, as a guest molecule. Stability constants were determined by the solubility method at various temperatures, and the thermodynamic parameters were calculated for inclusion complex formation in aqueous solution. The solid complexes were obtained in a molar ratio of 1:1, and their dissolution behavior and release from suppository bases were examined. The data suggest that the inclusion mode of the complex with 3 is somewhat different from that of the complexes with 1 and 2. From a practical point of view, 2 seems to be particularly useful for improving the pharmaceutical properties of flurbiprofen in various dosage forms.
Method for determination of optical purity of 2-arylpropanoic acids using urea derivatives based on a 1,1′-binaphthalene skeleton as chiral NMR solvating agents: Advantages and limitations thereof
Cu?ínová, Petra,Hájek, Peter,Jank?, Kristyna,Holakovsky, Roman
, p. 410 - 417 (2019)
Five optically active urea derivatives (1-5) were used as NMR solvating agents for analysis of the optical purity of different 2-arylpropanoic acids commonly used as nonsteroidal anti-inflammatory drugs. These novel chiral solvating agents were more efficient at discriminating the respective enantiomers of targets than the chiral solvating agents known so far, without the need to add a base for achieving the signal splitting. The advantages and limits of the use of these novel chiral solvating agents were studied.
An efficient method for the lipase-catalysed resolution and in-line purification of racemic flurbiprofen in a continuous-flow reactor
Tamborini, Lucia,Romano, Diego,Pinto, Andrea,Bertolani, Arianna,Molinari, Francesco,Conti, Paola
, p. 78 - 82 (2012)
The lipase-catalysed kinetic resolution of flurbiprofen was performed in a flow-chemistry reactor allowing for a significant reduction of the reaction time compared to the classical batch method. The process was implemented by adding an in-line purification step of the exiting solution, consisting in a catch and release protocol, which allows easy separation and recovery of both (S)-flurbiprofen and (R)-flurbiprofen butyl ester with an enantiomeric excess ≥90% and a chemical purity >98%.
Direct enantioselective HPLC monitoring of lipase-catalyzed kinetic resolution of flurbiprofen
Ghanem, Ashraf
, p. 597 - 603 (2010)
The solvent versatility of Chiralpak IB, a 3,5-dimethylphenylcarbamate derivative of cellulose-based chiral stationary phase, is demonstrated in the direct enantioselective HPLC monitoring of lipase-catalyzed kinetic resolution of flurbiprofen in nonstandard HPLC organic solvents. Nonstandard HPLC organic solvents were used as the reaction media for the lipase-catalysis and in mean time as diluent to dissolve the difficult to dissolve enzyme substrate (the acid) and as eluent for the simultaneous enantioselective HPLC baseline separation of both substrate and product in one run without any further derivatization.
Resolution of (R,S)-flurbiprofen catalysed by dry mycelia in organic solvent
Spizzo, Patrizia,Basso, Alessandra,Ebert, Cynthia,Gardossi, Lucia,Ferrario, Valerio,Romano, Diego,Molinari, Francesco
, p. 11005 - 11010 (2007)
Mycelia of Aspergillus oryzae display high enantioselectivity towards (R)-flurbiprofen and can be efficiently used in pure organic solvent for the resolution of (R,S)-flurbiprofen through esterification. The use of the lyophilized mycelia facilitates the separation process so that in one step the two enantiomers of flurbiprofen, which are both valuable for pharmaceutical applications, can be easily separated. The biotransformation can be carried out in different apolar solvents using different primary alcohols as nucleophiles under very mild conditions.
A Highly Enantioselective Alkene Methoxycarbonylation Enables a Concise Synthesis of (S)-Flurbiprofen
Harkness, Gavin J.,Clarke, Matthew L.
, p. 4859 - 4863 (2017)
A highly enantioselective synthesis of (S)-flurbiprofen methyl ester in two steps from commercially available 4-bromo-2-fluoro-1,1′-biphenyl is shown. [PdCl2((S)-xylyl-phanephos)] catalyst is used to accomplish both Grignard cross-coupling and the highly enantioselective intermolecular methoxycarbonylation reaction.
Enantioseparation of Racemic Flurbiprofen by Aqueous Two-Phase Extraction With Binary Chiral Selectors of L-dioctyl Tartrate and L-tryptophan
Chen, Zhi,Zhang, Wei,Wang, Liping,Fan, Huajun,Wan, Qiang,Wu, Xuehao,Tang, Xunyou,Tang, James Z.
, p. 650 - 657 (2015)
A novel method for chiral separation of flurbiprofen enantiomers was developed using aqueous two-phase extraction (ATPE) coupled with biphasic recognition chiral extraction (BRCE). An aqueous two-phase system (ATPS) was used as an extracting solvent which was composed of ethanol (35.0% w/w) and ammonium sulfate (18.0% w/w). The chiral selectors in ATPS for BRCE consideration were L-dioctyl tartrate and L-tryptophan, which were screened from amino acids, β-cyclodextrin derivatives, and L-tartrate esters. Factors such as the amounts of L-dioctyl tartrate and L-tryptophan, pH, flurbiprofen concentration, and the operation temperature were investigated in terms of chiral separation of flurbiprofen enantiomers. The optimum conditions were as follows: L-dioctyl tartrate, 80 mg; L-tryptophan, 40 mg; pH, 4.0; flurbiprofen concentration, 0.10 mmol/L; and temperature, 25 C. The maximum separation factor α for flurbiprofen enantiomers could reach 2.34. The mechanism of chiral separation of flurbiprofen enantiomers is discussed and studied. The results showed that synergistic extraction has been established by L-dioctyl tartrate and L-tryptophan, which enantioselectively recognized R- and S-enantiomers in top and bottom phases, respectively. Compared to conventional liquid-liquid extraction, ATPE coupled with BRCE possessed higher separation efficiency and enantioselectivity without the use of any other organic solvents. The proposed method is a potential and powerful alternative to conventional extraction for separation of various enantiomers. Chirality 27:650-657, 2015.
Different in vitro activity of flurbiprofen and its enantiomers on human articular cartilage
Panico,Cardile,Vittorio,Ronsisvalle,Scoto,Parenti,Gentile,Morrone,Nicolosi
, p. 1339 - 1344 (2003)
The 2-arylpropionic acid derivatives or 'profens' are an important group of non-steroidal anti-inflammatory drugs that have been used for the symptomatic treatment of various forms of arthritis. These compounds are chiral and the majority of them are stil
Chiral liquid chromatography-mass spectrometry (LC-MS/MS) method development with β-cyclodextrin (β-CD) derivatized chiral stationary phase for the enhanced separation and determination of flurbiprofen enantiomers: Application to a stereoselective pharmacokinetic study
Cai, Liangzhao,Guo, Xingjie,Liu, Beibei,Sun, Jiayi,Yu, Jia
, p. 10334 - 10342 (2020)
A method was developed and validated for the enantioselective determination of flurbiprofen in rat plasma using liquid chromatography/electrospray ionization-tandem mass spectrometry under reversed-phase elution mode. Two polysaccharide derivatized chiral stationary phases and a homemade β-cyclodextrin (β-CD) derivatized based chiral column were evaluated. The latter one, a per-4-chlorophenylcarbamate-β-cyclodextrin bonded chiral stationary phase which was synthesized in our laboratory, enabled the highly sensitive detection and complete separation (resolution 2.0) of the flurbiprofen enantiomers. The assay was carried out after the solid-phase extraction procedure with C18 cartridges, and with R-(-)-ibuprofen used as the internal standard. The developed method has been validated for specificity, linearity, accuracy, precision, recovery, matrix effect, stability, carryover effect and dilution effect. The lower limit of quantification for R-flurbiprofen and S-flurbiprofen was 10 ng mL-1 in rat plasma, respectively. Linearity was confirmed in the range of 10.0-20000.0 ng mL-1 with a correlation coefficient (r2) greater than 0.996. The established method was successfully applied to a stereoselective pharmacokinetic study of flurbiprofen enantiomers in rat plasma following oral administration. This journal is
