Lipase-Catalyzed Production of (S)-Carprofen Enhanced by Hydroxyethyl-β-cyclodextrins: Experiment and Optimization

Abstract

Stereoselective resolution of (R,S)-carprofen methyl ester (CPOMe) by lipase-catalyzed hydrolysis to (S)carprofen (CP) was investigated in an aqueous medium. With the highest catalytic activity, Candida antarctica Lipase A (CALA) was selected as catalyst compared with eight other lipases. Hydroxyethyl-β-cyclodextrin (HE-β-CD) was added to enhance the solubility of (R,S)-CPOMe, which significantly raised the conversion of substrate from 11.12% to 30.84%. Response surface methodology (RSM) was adopted to evaluate the influence of factors on the substrate conversion (c) and enantiomeric excess of product (ee p ), such as pH, concentrations of enzyme and HE-β-CD, temperature, substrate loading, and reaction time. The optimal conditions were obtained, including pH 6.0, 40 mg/mL CALA, 0.05 mmol substrate, 35 mmol/L HE-β-CD, agitation speed of 600 rpm, temperature of 76 °C, and reaction time of 30 h. Under the above conditions, (S)-CP as the desired product was obtained with an enantiomeric excess of 96.24% and overall conversion of 46.07%.

Morphological Evolution of Self-Assembled Sodium Dodecyl Sulfate/Dodecyltrimethylammonium Bromide@Epoxy-β-Cyclodextrin Supramolecular Aggregates Induced by Temperature

“…In contrast, the H5 protons were located inside the cavity and overlapped with the H6 protons located outside the cavity at the narrow end of the tapered cavity, yielding resonances of 3.75 and 3.77 ppm, respectively [36]. The H3 and H5 protons of β-CD molecules located in the cavity revealed the changes in the environment around the cavity caused by the entry of guest molecules, thus providing strong evidence for inclusion complex binding [38][39][40]. In the presence of the mixed SDS/DTAB surfactants, high-field chemical shift signals of the H3 and H5, which are located on the wide and narrow sides of the cavity, were observed.…”

Application of a Statistical Approach to the Process Development of Futibatinib by Employing Quality-by-Design Principles. Part 2: Development of Design Space for Impurities Using the Response Surface Methodology

“…RSM, which was developed by Box and Wilson, comprises statistical and mathematical techniques useful for developing, improving, and optimizing processes . Therefore, RSM has also been utilized to develop a manufacturing method for the supply of active pharmaceutical ingredients (API), and some manufacturing methods have been shown to be robust. − In RSM, selecting the method of DoE is important. Correct data analysis and regression diagnosis are essential for drawing appropriate conclusions from the experimental data, including accounting for errors.…”