Deeper Insight into the Six-Step Domino Reaction of Aldehydes with Malononitrile and Evaluation of Antiviral and Antimalarial Activities of the Obtained Bicyclic Products.

Journal article


Publication Details

Author(s): Bock C, Gangajji P, Bönisch S, Bauer W, Hutterer C, Leidenberger M, Friedrich O, Marschall M, Kappes B, Görling A, Tsogoeva S
Journal: ChemistryOpen
Publication year: 2017
Volume: 6
Journal issue: 3
Pages range: 364-374
ISSN: 2191-1363
Language: English


Abstract


The straightforward and efficient synthesis of complex aza- and carbobicyclic compounds, which are of importance for medicinal chemistry, is a challenge for modern chemical methodology. An unprecedented metal-free six-step domino reaction of aldehydes with malononitrile was presented in our previous study to provide, in a single operation, these bicyclic nitrogen-containing molecules. Presented here is a deeper investigation of this atom-economical domino process by extending the scope of aldehydes, performing post-modifications of domino products, applying bifunctional organocatalysts and comprehensive NMR studies of selected domino products. The thermodynamic aspects of the overall reaction are also demonstrated using DFT methods in conjunction with a semi-empirical treatment of van der Waals interactions. Furthermore, biological studies of seven highly functionalized and artemisinin-containing domino products against human cytomegalovirus (HCMV) and Plasmodium falciparum 3D7 are presented. Remarkably, in vitro tests against HCMV revealed five domino products to be highly active compounds (EC50 0.071-1.8 μm), outperforming the clinical reference drug ganciclovir (EC50 2.6 μm). Against P. falciparum 3D7, three of the investigated artemisinin-derived domino products (EC50 0.72-1.8 nm) were more potent than the clinical drug chloroquine (EC50 9.1 nm).



FAU Authors / FAU Editors

Bauer, Walter apl. Prof. Dr.
Lehrstuhl für Organische Chemie II
Bock, Christina
Lehrstuhl für Organische Chemie I
Bönisch, Simon
Lehrstuhl für Theoretische Chemie
Friedrich, Oliver Prof. Dr. Dr.
Lehrstuhl für Medizinische Biotechnologie
Gangajji, Parameshwarappa
Lehrstuhl für Organische Chemie I
Görling, Andreas Prof. Dr.
Lehrstuhl für Theoretische Chemie
Kappes, Bärbel Prof. Dr.
Lehrstuhl für Medizinische Biotechnologie
Leidenberger, Maria
Lehrstuhl für Medizinische Biotechnologie
Tsogoeva, Svetlana Prof. Dr.
Professur für Organische Chemie


How to cite

APA:
Bock, C., Gangajji, P., Bönisch, S., Bauer, W., Hutterer, C., Leidenberger, M.,... Tsogoeva, S. (2017). Deeper Insight into the Six-Step Domino Reaction of Aldehydes with Malononitrile and Evaluation of Antiviral and Antimalarial Activities of the Obtained Bicyclic Products. ChemistryOpen, 6(3), 364-374. https://dx.doi.org/10.1002/open.201700005

MLA:
Bock, Christina, et al. "Deeper Insight into the Six-Step Domino Reaction of Aldehydes with Malononitrile and Evaluation of Antiviral and Antimalarial Activities of the Obtained Bicyclic Products." ChemistryOpen 6.3 (2017): 364-374.

BibTeX: 

Last updated on 2019-20-07 at 07:21