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Lookup NU author(s): Dr Ahmad Al-Sheikh,
Dr Bian Zhang,
Dr Richard Lewis,
Dr Nicholas Allenby,
Dr Paul Waddell,
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.
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)
Online publication date: 11/12/2020
Acceptance date: 07/12/2020
Date deposited: 09/03/2021
ISSN (electronic): 1420-3049
Publisher: MDPI AG
PubMed id: 33322563
Notes: This article belongs to the Section Medicinal Chemistry.
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