Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents
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...
Published in: | Tetrahedron: Asymmetry |
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Format: | Article in Journal/Newspaper |
Language: | English |
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Online Access: | http://repo.lib.semmelweis.hu//handle/123456789/6337 https://doi.org/10.1016/j.tetasy.2015.04.013 |
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ftsemmelweisuniv:oai:repo.lib.semmelweis.hu:123456789/6337 2023-05-15T14:01:06+02:00 Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents Csuka Pál Boros Zoltán Őrfi László Dobos Judit Poppe László Hornyánszky Gábor SE/GYTK/Gyógyszerészi Kémiai Intézet Semmelweis Egyetem 2015 http://repo.lib.semmelweis.hu//handle/123456789/6337 https://doi.org/10.1016/j.tetasy.2015.04.013 en eng urn:issn:0957-4166 http://repo.lib.semmelweis.hu//handle/123456789/6337 doi:10.1016/j.tetasy.2015.04.013 2895911 000356557200008 Journal Article 2015 ftsemmelweisuniv https://doi.org/10.1016/j.tetasy.2015.04.013 2022-06-30T16:12:17Z 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. Article in Journal/Newspaper Antarc* Antarctica Semmelweis Egyetem: Repozitórium Tetrahedron: Asymmetry 26 12-13 644 649 |
institution |
Open Polar |
collection |
Semmelweis Egyetem: Repozitórium |
op_collection_id |
ftsemmelweisuniv |
language |
English |
description |
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. |
author2 |
SE/GYTK/Gyógyszerészi Kémiai Intézet Semmelweis Egyetem |
format |
Article in Journal/Newspaper |
author |
Csuka Pál Boros Zoltán Őrfi László Dobos Judit Poppe László Hornyánszky Gábor |
spellingShingle |
Csuka Pál Boros Zoltán Őrfi László Dobos Judit Poppe László Hornyánszky Gábor Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents |
author_facet |
Csuka Pál Boros Zoltán Őrfi László Dobos Judit Poppe László Hornyánszky Gábor |
author_sort |
Csuka Pál |
title |
Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents |
title_short |
Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents |
title_full |
Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents |
title_fullStr |
Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents |
title_full_unstemmed |
Chemoenzymatic route to Tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents |
title_sort |
chemoenzymatic route to tyrphostins involving lipase-catalyzed kinetic resolution of 1-phenylethanamine with alkyl cyanoacetates as novel acylating agents |
publishDate |
2015 |
url |
http://repo.lib.semmelweis.hu//handle/123456789/6337 https://doi.org/10.1016/j.tetasy.2015.04.013 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
urn:issn:0957-4166 http://repo.lib.semmelweis.hu//handle/123456789/6337 doi:10.1016/j.tetasy.2015.04.013 2895911 000356557200008 |
op_doi |
https://doi.org/10.1016/j.tetasy.2015.04.013 |
container_title |
Tetrahedron: Asymmetry |
container_volume |
26 |
container_issue |
12-13 |
container_start_page |
644 |
op_container_end_page |
649 |
_version_ |
1766270623909150720 |