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Synthesis of Important Chiral Building Blocks for Pharmaceuticals Using Lactobacillus and Rhodococcus Alcohol Dehydrogenases
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marion Rauter, Simon Krebs, Gotthard Kunze
The separation of both enantiomers from a racemic mixture by chiral chromatography or chiral resolution as required after chemical synthesis is cumbersome and costly. Maximum yield is low with about 50% with regard to substrate concentration. Although optically active catalysts such as 2,2′–bis(diphenylphosphino)–1,1′–binaphthyl (BINAP) are available, they are expensive and require the use of physiologically problematic noble or transition metals (Sheldon, 2008).
Pharmacokinetics, mass balance, metabolism, and excretion of the liver-targeted acetyl-CoA carboxylase inhibitor PF-05221304 (clesacostat) in humans
Published in Xenobiotica, 2022
Tim F. Ryder, Arthur Bergman, Amanda King-Ahmad, Neeta B. Amin, Manjinder S. Lall, T. Eric Ballard, Amit S. Kalgutkar
Before analysis, the human faecal extract, urine pool, and plasma extracts were diluted 10 times with acetonitrile. Chiral chromatography on a SFC chromatographic system was used to compare the relative amounts of m/z 519 comprising of the individual enantiomers PF-07229833 (M2a) and PF-07229579 (M2b). Faecal homogenate extracts and urine were analysed using a Chiral Tech AD-3 4.6 × 250 mm, 5 µm analytical column to separate the enantiomers. The column was connected to an Agilent Technologies 1260 infinity hybrid SFC/UPLC system, operated in the SFC mode. Mobile phase was run isocratic at a flow rate of 3.0 ml/minute with 35% supercritical CO2 and 65% methanol with 0.2% isopropylamine. The column Temperature was set to 60 °C. A Sciex API5500 operating in MRM mode (declustering potential = 100 and collision energy = 45), monitoring the m/z 519.0/443.0 transition was used to detect the metabolites. The MRM area ratio of PF-07229833 and PF-07229579 was used to split the liquid scintillation counts between the respective metabolites in the achiral HPLC method.