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

Pál Csuka, Zoltán Boros, László Orfi, Judit Dobos, László Poppe, Gábor Hornyánszky

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 various aromatic 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 μM), none of them proved to have a significant effect on the growth of the investigated cell lines.

Original languageEnglish
Pages (from-to)644-649
Number of pages6
JournalTetrahedron Asymmetry
Volume26
Issue number12-13
DOIs
Publication statusPublished - Jan 1 2015

ASJC Scopus subject areas

  • Catalysis
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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