Structural Analysis of the Michael-Michael Ring Closure (MIMIRC) Reaction Products.

A representative number of decalin and hydrindane derivatives 2a-l were prepared in 11-91% yield by means of a cascade reaction of cyclohexanone/cyclopentanone enolates and methyl acrylate through a Michael-Michael ring closure (MIMIRC) process. The relative stereochemistry of the four stereogenic centers formed in all products was determined by analyzing the vicinal coupling constants from the 1H NMR and X-ray crystallography. Such a stereochemical outcome was corroborated by conformational analysis supported by DFT calculations and simulating the 1H NMR spectra of representative products. All products showed the same relative stereochemistry at C-1 and C-8a, while at C-3 and bridgehead carbon C-4a, configurational changes were observed. The present results provide some insights about the scope and limitations of the triple cascade reaction between cycloalkanone enolates with methyl acrylate. This synthetic protocol is still a simple and very practical alternative to generate decalin and hydrindane derivatives with great structural diversity.

Imidazolines as non-classical bioisosteres of N-acyl homoserine lactones and quorum sensing inhibitors.

A series of selected 2-substituted imidazolines were synthesized in moderate to excellent yields by a modification of protocols reported in the literature. They were evaluated as potential non-classical bioisosteres of AHL with the aim of counteracting bacterial pathogenicity. Imidazolines 18a, 18e and 18f at various concentrations reduced the violacein production by Chromobacterium violaceum, suggesting an anti-quorum sensing profile against Gram-negative bacteria. Imidazoline 18b did not affect the production of violacein, but had a bacteriostatic effect at 100 µM and a bactericidal effect at 1 mM. Imidazoline 18a bearing a hexyl phenoxy moiety was the most active compound of the series, rendering a 72% inhibitory effect of quorum sensing at 100 µM. Imidazoline 18f bearing a phenyl nonamide substituent presented an inhibitory effect on quorum sensing at a very low concentration (1 nM), with a reduction percentage of 28%. This compound showed an irregular performance, decreasing inhibition at concentrations higher than 10 µM, until reaching 100 µM, at which concentration it increased the inhibitory effect with a 49% reduction percentage. When evaluated on Serratia marcescens, compound 18f inhibited the production of prodigiosin by 40% at 100 µM.