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Molecular Diversity via Tetrasubstituted Alkenes Containing a Barbiturate Motif: Synthesis and Biological Activity

Lookup NU author(s): Dr Ahmad Al-Sheikh, Masuma Begum, Dr Bian Zhang, Dr Richard Lewis, Dr Nicholas Allenby, Dr Paul Waddell, Emeritus Professor Bernard Golding



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


The synthesis of a molecularly diverse library of tetrasubstituted alkenes containing a barbiturate motif is described. Base-induced condensation of N1-substituted pyrimidine-2,4,6(1H,3H,5H)-triones with 5-(bis(methylthio)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-substituted 5-(methylthio)-2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones ('pyranopyrimidinones'), regioselectively. A sequence of reactions involving ring-opening of the pyran moiety, displacement of the methylthio group with an amine, re-formation of the pyran ring, and after its final cleavage with an amine, gave tetrasubstituted alkenes (3-amino-3-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)propanamides) with a diversity of substituents. Cleavage of the pyranopyrimidinones with an aniline was facilitated in 2,2,2-trifluoroethanol under microwave irradiation. Compounds were tested against Escherichia coli, Staphylococcus aureus, the yeast Schizosaccharomyces pombe, and the pathogenic fungus Candida albicans. No compounds exhibited activity against E. coli, whilst one compound was weakly active against S. aureus. Three compounds were strongly active against S. pombe, but none was active against C. albicans.

Publication metadata

Author(s): Al-Sheikh A, Begum M, Zhang B, Lewis RA, Allenby NEE, Waddell PG, Golding BT

Publication type: Article

Publication status: Published

Journal: Molecules (Basel, Switzerland)

Year: 2020

Volume: 25

Issue: 24

Online publication date: 11/12/2020

Acceptance date: 07/12/2020

Date deposited: 09/03/2021

ISSN (electronic): 1420-3049

Publisher: MDPI AG


DOI: 10.3390/molecules25245868

PubMed id: 33322563

Notes: This article belongs to the Section Medicinal Chemistry.


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