China
Africa
Explore chapters and articles related to this topic
Hydrolytic Enzymes for the Synthesis of Pharmaceuticals
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Sergio González-Granda, Vicente Gotor-Fernández
Mandelic acid is a common scaffold for the synthesis of a wide range of chiral drugs, so the formation of optically active forms has been extensively described in the literature. One recent example consists of the resolution of mandelic acid methyl esters via O-acylation (Poterala et al., 2017). A series of mandelic acid derivatives bearing different substitutions in the aromatic ring have been efficiently resolved with either the Amano AK from Pseudomonas fluorescens lipase or different immobilised forms of PSL (Scheme 9.25). Best conditions were found using vinyl acetate and TMBE for the synthesis of the corresponding (S)-acetates and (R)-alcohols in good to excellent selectivities at room temperature using 3.5 of substrate. Taking advantage of one of this stereoselective processes, the chemoenzymatic preparation of enantiopure (R)-Pemoline was developed, which is a stimulant drug from the 4-oxazolidinone class. KR of racemic mandelic acid for the synthesis of the stimulant (R)-Pemoline.
Recent trends in the treatment of cyanide-containing effluents: Comparison of different approaches
Published in Critical Reviews in Environmental Science and Technology, 2023
Ludmila Martínková, Pavla Bojarová, Anastasia Sedova, Vladimír Křen
The products of the cyanation of aldehydes and ketones are cyanohydrins, which are intermediates for fine and pharmaceutical chemicals. For example, mandelonitrile has been obtained by cyanation of benzaldehyde and used to produce mandelic acid (chiral resolving agent, chiral building block). This product is often required in an enantiopure form, such as (R)-mandelic acid, which can be prepared by biocatalytic hydrolysis of racemic mandelonitrile (Martínková & Křen, 2018). (R)-2-Chloromandelic acid can be prepared analogously and is a precursor of the antithrombotic drug clopidogrel (Zou et al., 2021). Cyanation of acetone gives acetone cyanohydrin, a precursor of methyl methacrylate, which is used for the production of polymethyl methacrylate (PMMA) known as, e.g., acrylic or “Plexiglas”.
Aqueous Biphasic Systems Using Chiral Ionic Liquids for the Enantioseparation of Mandelic Acid Enantiomers
Published in Solvent Extraction and Ion Exchange, 2018
Francisca A. e Silva, Mariam Kholany, Tânia E. Sintra, Magda Caban, Piotr Stepnowski, Sónia P. M. Ventura, João A. P. Coutinho
Mandelic acid enantiomers were quantified by HPLC-DAD using an analytical method adapted from Yue et al. with modifications.[48] The liquid chromatograph HPLC Elite LaChrom (VWR Hitachi) used for this purpose was equipped with a diode array detector (DAD) l-2455, column oven l-2300, auto-sampler l-2200 and pump l-2130. A C18 reversed-phase analytical column (LiChrospher 100 RP-18, 5 µm, 250 mm × 4 mm i.d.) linked to a guard column (5 µm, 4 mm × 4 mm) with the same stationary phase was used. The column oven and autosampler were operated at controlled temperature of 22°C and 25°C, respectively. The mobile phase was made up of water:methanol [85:15 (v/v)], 2 mM L-phenylalanine and 1 mM CuSO4 at pH = 4.00 (±0.02), adjusted by adding an ammonia aqueous solution at 5 wt%. The separation was carried out using isocratic elution at a flow rate of 0.8 mL.min−1 and the injection volume was 20 µL. DAD was set to measure the spectrum from 200 to 600 nm, with a specific wavelength of 270 nm being used for R-mandelic acid and S-mandelic acid quantification. Calibration curves were previously determined using stock solutions prepared in water:methanol [85:15 (v/v)] at concentrations of 10–500 µg.mL−1 of each enantiomer. The R enantiomer elutes first, at a retention time of around 11.7 min, followed by S eluting at approximately 13.2 min. The LOD and LOQ were, respectively, 5 µg.mL−1 and 10 µg.mL−1 for both enantiomers. Intra- and inter-day precisions were 0.27–3.29 % and 1.39–1.88 % for R-MA and 0.79–5.59 % and 4.01–6.40 % for S-MA, respectively. Intra and inter-day accuracies were 95.8–127 % and 96.4–118.4 % for R-MA, while for S-MA they were of 97.3–126.2 % and 93.0–124.6%, respectively. The CIL-rich phases were diluted using water:methanol [85:15 (v/v)] and filtered using syringe filters (0.45 µm). At least two injections per sample were done.