14035-96-2Relevant articles and documents
A Biocatalytic Route to the Novel Antiepileptic Drug Brivaracetam
Schülé, Arnaud,Merschaert, Alain,Szczepaniak, Christophe,Maréchal, Christophe,Carly, Nicolas,O'Rourke, John,Ates, Célal
, p. 1566 - 1575 (2016)
An asymmetric synthesis of the novel antiepileptic drug Brivaracetam 1 is described. The stereochemistry of the 4-n-propyl substituent is introduced by a biocatalytic resolution of (rac)-methyl 2-propylsuccinate 4-tert-butyl ester 4. The selection of the resolution substrate and the screening of enzymes were carried out from our in-house screening platform. The development and scale-up of the best conditions, including solvent media, pH control, workup, and enzyme supply, led up to a successful demonstration conducted at 1 kg scale in a 10 L vessel. The chiral intermediate (R)-2-propylsuccinic acid 4-tert-butyl ester 6 was reproducibly obtained in 42% yield and 97% ee all along the development. The control of the stereochemistry via the biocatalytic resolution allowed the production of Brivaracetam 1 within the required commercial quality specifications.
Synthesis of Enantiomerically Enriched 2-Hydroxymethylalkanoic Acids by Oxidative Desymmetrisation of Achiral 1,3-Diols Mediated by Acetobacter aceti
Brenna, Elisabetta,Cannavale, Flavia,Crotti, Michele,De Vitis, Valerio,Gatti, Francesco G.,Migliazza, Gaia,Molinari, Francesco,Parmeggiani, Fabio,Romano, Diego,Santangelo, Sara
, p. 3796 - 3803 (2016/12/24)
The stereoselective desymmetrisation of achiral 2-alkyl-1,3-diols is performed by oxidation of one of the two enantiotopic primary alcohol moieties by means of Acetobacter aceti MIM 2000/28 to afford the corresponding chiral 2-hydroxymethyl alkanoic acids (up to 94 % ee). The procedure, carried out in aqueous medium under mild conditions of pH, temperature and pressure, contributes to enlarge the portfolio of enzymatic oxidations available to organic chemists for the development of sustainable manufacturing processes.
Unprecedented hydrogen transfer from water to alkenes and alkynes mediated by TiIII and late transition metals
Campana, Araceli G.,Estevez, Rosa E.,Fuentes, Noelia,Rubles, Rafael,Cuerva, Juan M.,Bunuel, Elena,Cardenas, Diego,Oltra, J. Enrique
, p. 2195 - 2198 (2008/02/04)
We describe how alkenes and alkynes can be hydrogenated under mild conditions by hydrogen transfer from water mediated by titanocene(III) and a substoichiometric quantity of one of the late transition metals usually employed as hydrogenation catalysts. This process proceeds presumably by H-atom transfer from TiIII-coordinated water to the late transition metal partner (depicted in the drawing above), a mechanism in support of which we provide theoretical and experimental evidence.