Formation of 5-Aminomethyl-2,3-dihydropyridine-4(1 H)-ones from 4-Amino-tetrahydropyridinylidene Salts

Abstract

Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in an alkaline medium. Their conversion to 5-substituted β-hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted β-aminoketones or a single δ-diketone. The new compounds were characterized using spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.

Keywords: antibacterial; anticancer activity; dihydropyridin-4(1H)-ones; tetrahydropyridinylidene salts.

Scheme 1

Syntheses of 2,3-dihydropyridin-4(1H)-ones [12,13,14].

Figure 1

Compounds containing the 2,3-dihydropyridin-4(1H)-one motif [24,25,26,27].

Scheme 2

Synthesis of compounds 2–12.

Scheme 3

Synthesis of δ-diketones 13 and 14 with electron-sufficient aldehydes.

Scheme 4

Control experiments with dihydropyridone 15.

Scheme 5

Possible mechanisms of the formation of compounds 2–14.

Figure 2

Through-space couplings indicated as arrows in compound 2a.

Figure 3

Stereoscopic ORTEP [28] plot of 6a showing the atomic numbering scheme. The probability ellipsoids are drawn at the 50% probability level. The H atoms are drawn with arbitrary radii. Nitrogen atoms are blue, oxygen atoms are red.

Figure 4

Anti-proliferative activity of compounds 2b–14 against human leukemia cell line CCRF-CEM (A) and against non-tumorigenic MRC-5 lung fibroblasts (B) expressed as mean ± SEM. Cells were treated with 50 and 5 µM of the compounds for 72 h. Cell viability was measured via XTT assay. Viability rates were expressed as a percentage of vehicle-treated control cells (0.1% DMSO). Vinblastine (VB) at a concentration of 100 nM served as positive control.