One-Pot Lipase-Catalyzed Enantioselective Synthesis of (R)-(−)-N-Benzyl-3-(benzylamino)butanamide: The Effect of Solvent Polarity on Enantioselectivity
Marina A. Ortega-Rojas,
José Domingo Rivera-Ramírez,
C. Gabriela Ávila-Ortiz,
Eusebio Juaristi,
Fernando González-Muñoz,
Edmundo Castillo,
Jaime Escalante
Affiliations
Marina A. Ortega-Rojas
The Center for Chemical Research, Autonomous University of Morelos State, Avenida Universidad 1001, Chamilpa, Cuernavaca 62210, Mexico
José Domingo Rivera-Ramírez
The Center for Chemical Research, Autonomous University of Morelos State, Avenida Universidad 1001, Chamilpa, Cuernavaca 62210, Mexico
C. Gabriela Ávila-Ortiz
Departamento de Química, Centro de Investigación y de Estudios Avanzados, Avenida I.P.N. 2508, Ciudad de México 07360, Mexico
Eusebio Juaristi
Departamento de Química, Centro de Investigación y de Estudios Avanzados, Avenida I.P.N. 2508, Ciudad de México 07360, Mexico
Fernando González-Muñoz
Department of Cell Engineering and Biocatalysis, Institute of Biotechnology, UNAM, Apartado Postal 510-3, Cuernavaca C.P. 62271, Mexico
Edmundo Castillo
Department of Cell Engineering and Biocatalysis, Institute of Biotechnology, UNAM, Apartado Postal 510-3, Cuernavaca C.P. 62271, Mexico
Jaime Escalante
The Center for Chemical Research, Autonomous University of Morelos State, Avenida Universidad 1001, Chamilpa, Cuernavaca 62210, Mexico
The use of the solvent engineering has been applied for controlling the resolution of lipase-catalyzed synthesis of β-aminoacids via Michael addition reactions. The strategy consisted of the thermodynamic control of products at equilibrium using the lipase CalB as a catalyst. The enzymatic chemo- and enantioselective synthesis of (R)-(−)-N-benzyl-3-(benzylamino)butanamide is reported, showing the influence of the solvent on the chemoselectivity of the aza-Michael addition and the subsequent kinetic resolution of the Michael adduct; both processes are catalyzed by CalB and both are influenced by the nature of the solvent medium. This approach allowed us to propose a novel one-pot strategy for the enzymatic synthesis of enantiomerically enriched β-aminoesters and β-aminoacids.
