Enantioselective synthesis of 4-amino-3,4-dihydrocoumarins and their non-cyclic hydroxyester precursors: Biological evaluation for the treatment of glioblastoma multiforme.

Autor: Borrego LG; Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González, 2, 41012, Sevilla, Spain., Recio R; Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González, 2, 41012, Sevilla, Spain. Electronic address: rrecioj@us.es., Moreno N; Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González, 2, 41012, Sevilla, Spain., Chelouan A; Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González, 2, 41012, Sevilla, Spain., Álvarez E; Instituto de Investigaciones Químicas, CSIC-Universidad de Sevilla, Avda. Américo Vespucio, 49, 41092, Sevilla, Spain., Sánchez-Coronilla A; Departamento de Química Física, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González, 2, 41012, Sevilla, Spain., Caro C; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), C/ Severo Ochoa, 35, 29590, Málaga, Spain., Pearson JR; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), C/ Severo Ochoa, 35, 29590, Málaga, Spain., García-Martín ML; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (IBIMA Plataforma BIONAND), C/ Severo Ochoa, 35, 29590, Málaga, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN), Spain., Khiar N; Instituto de Investigaciones Químicas, CSIC-Universidad de Sevilla, Avda. Américo Vespucio, 49, 41092, Sevilla, Spain., Fernández I; Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, C/ Profesor García González, 2, 41012, Sevilla, Spain.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2022 Dec 05; Vol. 243, pp. 114730. Date of Electronic Publication: 2022 Sep 01.
DOI: 10.1016/j.ejmech.2022.114730
Abstrakt: The stereoselective addition of ethyl acetate enolate to the C═N bond of N-tert-butylsulfinylimines has been investigated in depth. A significant effect of the LHMDS amount and the N-sulfinylimine nature on the stereoselectivity of the process was observed. Conditions were found where sulfinylimines of differently substituted salicylaldehydes derivatives, ethyl acetate, and LHMDS afforded the corresponding addition products as a single diastereomer in good yields. The developed protocol was successfully applied to the first stereoselective synthesis of differently substituted 4-amino-3,4-dihydrocoumarin derivatives. Computational models confirmed the prominent role of the ortho aryl substituent in the stereoselectivity of the process. A significant and selective cytotoxic activity against Glioblastoma Multiforme (GBM) cancer line has been determined for the noncyclic hydroxy ester derivative.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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