Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents

• Published in: Tetrahedron: Asymmetry
• Main Authors: Csuka Pál, Boros Zoltán, Őrfi László, Dobos Judit, Poppe László, Hornyánszky Gábor
• Other Authors: SE/GYTK/Gyógyszerészi Kémiai Intézet, Semmelweis Egyetem
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2015
• Subjects: Antarc*; Antarctica
• Online Access: http://repo.lib.semmelweis.hu//handle/123456789/6337; https://doi.org/10.1016/j.tetasy.2015.04.013

Ethyl and isopropyl cyanoacetates were tested as acylating agents in the kinetic resolution of racemic 1-phenylethanamine rac-1 catalyzed by lipase B from Candida antarctica. The best conversion combined with high enantioselectivity was achieved with ethyl cyanoacetate 2a as the acylating agent and immobilized lipase B from Candida antarctica (CaLB N435) as the biocatalyst. Enantiomers of the amides (R)-3 and (S)-3 were obtained with high enantiopurity (ee >98%) by lipase-catalyzed kinetic resolution and by chemical conversion of the residual (S)-1, respectively. The amides were reacted with variousaromatic aldehydes 4a–c,e in Knoevenagel condensation to yield Tyrphostins rac-5a–c,e, (R)-5a–c,e and (S)-5a–c,e, which were tested as protein tyrosine kinase inhibitors on human cancer cell lines HCT 116, A549, PC9, PC9ER, Jurkat, and MV4-11. Although some of the novel Tyrphostins exhibited weak biological activities (EC50 6–60 lM), none of them proved to have a significant effect on the growth of the investigated cell lines.