No abstract

Dihydropyrimidinone/thiones (DHPMs) are heterocycles widely explored due to their ability to interact with different pharmacological targets. We report herein the C-N axial chirality in a DHPM scaffold with the presence of various substituents at the ortho-position of the aromatic ring linked to the N1. This structural feature produced atropisomerism due to the restricted rotation around the CÀ N bond. The atropisomerism in DHPMs was investigated by NMR, HPLC, and in silico experiments. The effect of the solvent, microwave radiation, temperature, and substituent at the ortho position on the selectivity of the reaction was examined.

The practical two-step synthesis of 1-phenylthiourea is reported here as an undergraduate experiment for the organic synthesis laboratory. The reactions involved in 1-phenylthiourea preparation are very useful didactic examples to illustrate concepts relating to carbonyl substitution and addition, the effect of pH on solubility of organic compounds, and many laboratory techniques, such as isolation, purification, and product analysis. The products were purified through precipitation, which involves changing the pH value, followed by recrystallization. The products were identified by melting point and infrared and NMR spectroscopy.

The Biginelli reaction is an acid-catalyzed, three-component reaction between an aldehyde, a hydrogen methylene active compound, and urea (or its analogue) and constitutes a rapid and easy synthesis of highly functionalized heterocycles. Synthesis of ethyl 6-methyl-2-oxo-4-{4-[(1-phenyl-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-1,2,3,4-tetrahydropyrimidine-5-carboxylate, identified by our laboratory code LaSOM® 293, was achieved using the Biginelli reaction as the key step, followed by the Huisgen 1,3-dipolar cycloaddition in a convergent four-step route. The product LaSOM® 293 was obtained with a yield of 84%.

: Dihydropyrimidinones (DHPMs) are heterocycles obtained by the multicomponent Biginelli reaction. Recently, new synthetic protocols have allowed us to explore functionalisation at less explored positions of DHPMs, such as the N1 position. In this context, we have performed a full literature survey of N1-substituted DHPMs. We analysed 27 papers and identified 379 compounds with substituents at the N1 position, most of them with alkyl groups, and of 28% with aromatic substituents attached at the N1 position. N1-substituted DHPMs are explored mainly due to their effects on cancer cell proliferation via numerous targets, such as kinesin Eg5, heat shock protein 70, heat shock protein 90 and the epidermal growth factor receptor. Similarity analyses were performed using the data of 379 DHPMs from different cheminformatic approaches, i.e. chemical property correlations, principal component analysis, similarity networks and compound clustering.