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

TETRAHEDRON

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Article

da Silva, Marcos Reinaldo¹  de Mattos, Marcos Carlos¹  Ferreira de Oliveira, Maria da Conceicao¹  Gomes de Lemos, Telma Leda¹  Pontes Silva Ricardo, Nagila Maria¹  de Gonzalo, Gonzalo²  Lavandera, Ivan²  Gotor-Fernandez, Vicente²  Gotor, Vicente² 

[1] Univ Fed Ceara, Dept Quim Organ & Inorgan, BR-60451970 Fortaleza, Ceara, Brazil

[2] Univ Oviedo, Inst Univ Biotecnol Asturias, Dept Quim Organ & Inorgan, E-33006 Oviedo, Spain

关键词: Amino acids;    Asymmetric synthesis;    Interesterification;    Kinetic resolution;    Lipases;   

DOI  :  10.1016/j.tet.2014.02.012

来源: Elsevier

【 摘 要 】

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. (c) 2014 Elsevier Ltd. All rights reserved.

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