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
Brivaracetam, namely (2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide is a novel antiepileptic drug approved for the treatment of partial onset seizures in patients with epilepsy. The enzymatic resolutions of ester precursors have been described through hydrolytic procedures (Scheme 9.3). After a screening of 30 esterases, 30 lipases, 15 proteases and one acylase, Bacillus subtilis protease was selected as the most stereoselective catalyst in a phosphate buffer at pH 7.5 (Schülé et al., 2016). Remarkably, the ethyl ester was effectively hydrolysed, keeping untouched the tert-butyl ester group. The protease C from Bacillus subtilis allowed the access to the remaining (S)-ester in 99% ee and the (R)-succinic acid in 95% ee (E = 210) using acetone as cosolvent. Further studies related to the reaction conditions were undertaken, searching for ideal scale-up conditions including the work-up and isolation of the optically active products. Special efforts were done in the replacement of the phosphate buffer used in the screenings by water, so the best conditions for the 1 kg substrate biotransformation yielded 394.4 g of the (R)-2-propylsuccinic acid 4-tert-butyl ester in 97% ee and 42% final yield. Protease-catalysed KR of a Brivaracetam precursor by hydrolysis in water.
Tribo-electrification of pharmaceutical powder blends
Published in Particulate Science and Technology, 2019
Antonella Rescaglio, Frederic De Smet, Luc Aerts, Geoffoy Lumay
Brivaracetam ((2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide; trade name Briviact®), a chemical analog of levetiracetam, is also an antiepileptic drug used for uncontrolled partial epilepsy in adults, Matagne et al. (2008).