Asymmetric chemoenzymatic synthesis of N-acetyl-alpha-amino esters based on lipase-catalyzed kinetic resolutions through interesterification reactions

作者：da Silva Marcos Reinaldo; de Mattos Marcos Carlos; Ferreira de Oliveira Maria da Conceicao; Gomes de Lemos Telma Leda; Pontes Silva Ricardo Nagila Maria; de Gonzalo Gonzalo; Lavandera Ivan; Gotor Fernandez Vicente; Gotor Vicente^*

来源：Tetrahedron, 2014, 70(13): 2264-2271.

DOI：10.1016/j.tet.2014.02.012

• Amino acids
• Asymmetric synthesis
• Interesterification
• Kinetic resolution
• Lipases

Several phenylalanine analogs have been synthesized through a four-step route starting from easily available ethyl acetamidocyanoacetate. In a first reaction, and making use of phase transfer catalysts, this compound reacted with several alkyl halides, being benzyltributylammonium chloride identified as the best one for the production of a series of quaternary amino acids in moderate to excellent yields (52-95%). Then, the corresponding N-acetyl-phenylalanine methyl and allyl ester derivatives were obtained through acidic hydrolysis, esterification, and N-acetylation. Rhizomucor miehei lipase was found as a versatile enzyme for the resolution of these amino esters, finding the best results through interesterification reactions with butyl butyrate in acetonitrile. A great influence in the stereoselectivity was found depending on the chemical structure of the compound, achieving for the non- or para-substituted in the phenyl ring excellent stereoselectivities, being moderate for the meta-nitro derivative, while the ortho-nitro amino ester did not react.

• 出版日期2014-4-1