Enzymatic Desymmetrisation of Prochiral <i>meso</i>-1,2-Disubstituted-1,2-Diaminoethane for the Synthesis of Key Enantioenriched (−)-Nutlin-3 Precursor
Virginia Cristofori,
Davide Illuminati,
Chiara Bisquoli,
Martina Catani,
Greta Compagnin,
Giulia Turrin,
Claudio Trapella,
Anna Fantinati
Affiliations
Virginia Cristofori
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy
Davide Illuminati
Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 213/d, 41125 Modena, Italy
Chiara Bisquoli
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy
Martina Catani
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy
Greta Compagnin
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy
Giulia Turrin
Department of Environmental and Prevention Sciences, University of Ferrara, Corso Ercole I d’Este, 32, 44121 Ferrara, Italy
Claudio Trapella
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, 44121 Ferrara, Italy
Anna Fantinati
Department of Environmental and Prevention Sciences, University of Ferrara, Corso Ercole I d’Este, 32, 44121 Ferrara, Italy
Herein we present the biocatalysed preparation of a mono-N-carbamate-protected precursor of antitumoral Nutlin-3a through enantioselective alkoxycarbonylation of meso-1,2-disubstituted-1,2-diaminoethane using enzyme lipases and dialkyl carbonates as acylating agents. A series of supported or free lipase enzymes were screened in combination with commercially available diallyl, diethyl and dimethyl carbonates. The reactions were conducted at different temperatures, for different reaction times and with variable co-solvent systems to evaluate the effects on the enzyme catalytic activity. The best results in terms of conversion, enantiomeric excess and yield were obtained when lipase from Candida antarctica B (CAL-B) was used with diallyl carbonate (DAC) when conducting the reaction solventless at 75 °C.
