Articolo in rivista, 2014, ENG, 10.1016/j.molcatb.2014.03.015

Milnacipran as a challenging example of aminomethyl substrate for lipase-catalyzed kinetic resolution

Sanfilippo C.; Nicolosi G.; Patti A.

Istituto di Chimica Biomolecolare Del CNR, Via Paolo Gaifami 18, Catania, 95126, Italy

A biocatalysed procedure for the kinetic resolution of milnacipran, (±)-1 was developed and optimized by careful choice of the reaction parameters. The reaction of (±)-1 with methyl iso-butyrate as acyl donor in the presence of Novozyme 435 in tert-butyl methyl ether proceeded with moderate enantioselectivity giving the more pharmacologically active enantiomer of milnacipran (-)-1 as unreacted substrate and the corresponding amide (-)-4 both in optically enriched form. When the enzymatic reaction was prolonged up to 65% substrate conversion enantiopure levomilnacipran (-)-1 (98% ee) was directly recovered from the reaction mixture by simple extraction workup. © 2014 Published by Elsevier B.V.

Journal of molecular catalysis. B, Enzymatic (Print) 104 , pp. 82–86

Keywords

Aminolysis, Chiral amines, Kinetic resolution, Levomilnacipran, Lipase

CNR authors

Sanfilippo Claudia, Nicolosi Giovanni, Patti Angela

CNR institutes

ICB – Istituto di chimica biomolecolare