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Lipase-Mediated Biocatalysis as a Greener and Sustainable Choice for Pharmaceutical Processes
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Monika Sharma, Tanya Bajaj, Rohit Sharma
Rasagiline mesylate or R-(+)-N-propargyl-1-aminoindean mesylate is the active pharmaceutical ingredient of the drug Azilect® that is used for the treatment of Parkinson’s disorder (Fernández et al., 2011). This potent drug is a second-generation propargylamine pharmacophore that selectively and irreversibly inhibits the monoamine oxidase enzyme (MAO-B only, and not MAO-A). Like many other chiral drugs and APIs, the S-f-J-enantiomer of N-propargyl-1-aminoindane does show activity against MAO-B but the R-(+)-enantiomer is a 1000-fold more potent. The API is synthesized chemoenzymatically by using immobilized lipase from Thermomyces lanuginosus (TLL) (Fig. 1.18) and lipase AK from Pseudomonas fluorescens to produce (S)-indanol. The acetylations were carried out in the presence of acetonitrile, tetrahydrofuran, hexane and toluene as the organic solvents and vinyl acetate as the acylating agent (Fonseca et al., 2015).
Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle
Published in Journal of Dispersion Science and Technology, 2019
Kevin F. Morris, Eugene J. Billiot, Fereshteh H. Billiot, Jordan A. Ingle, Kevin B. Krause, Corbin R. Lewis, Kenny B. Lipkowitz, William M. Southerland, Yayin Fang
The enantiomers of chiral drugs often have different potencies, toxicities, and biochemical properties. For example, the l-enantiomer of dopamine calms tremors, whereas the d-enantiomer is toxic to nerve cells.[1,2] Therefore, the FDA and other worldwide regulatory agencies require manufactures to test and prove the enantiomeric purity of chiral drugs.[3] This requirement has led to the development of many chiral chromatographic techniques using thin layer chromatography, gas chromatography, high-performance liquid chromatography, and capillary electrophoresis (CE)-based methods.[4,5] In each of these techniques, (R) and (S) enantiomers in a racemic mixture are separated based upon the often small differences in their interactions with other chiral molecules making up the chromatographic stationary or pseudostationary phases.
Investigation of chiral recognition by molecular micelles with molecular dynamics simulations
Published in Journal of Dispersion Science and Technology, 2018
Kevin F. Morris, Eugene J. Billiot, Fereshteh H. Billiot, Jordan A. Ingle, Stephanie R. Zack, Kevin B. Krause, Kenny B. Lipkowitz, William M. Southerland, Yayin Fang
Separation of the enantiomers of both natural and synthetic chiral compounds is a continuing challenge in many areas of chemistry. For example, in the medical and pharmaceutical fields, it is well known that the enantiomers of chiral drugs often have different physiological activity.[1,2] Since 1994, the United States Food and Drug Administration has required the separate testing of the optical isomers of all drugs that exist in enantiomeric form.[3] Consequently, there is a need for efficient chiral chromatographic techniques to separate drug enantiomers.[4,5] These separations are challenging because they are based on small differences in binding free energies between analyte enantiomers and the separation medium.[6,7] This small difference in binding energies is what often makes capillary electrophoresis (CE) an ideal method for enantiomeric separations.