Synthesis, structure and antimicrobial activity of 6-(propan-2-yl)-3-methyl-morpholine-2,5-dione

Cyclodepsipeptides are known to exhibit a broad spectrum of biological activities and present a great potential for pharmacological application. A novel didepsipeptide member of the family, 6-(propan-2-yl)-3-methyl-morpholine-2,5-dione, was synthesized and its structure was confirmed by IR, H-1 and C-13 NMR spectral data. The structure and relative stability of the diastereoisomers, tautomers and anionic derivatives of 6-(propan-2-yl)-3-methyl-morpholine-2,5-dione were studied by DFT. Different conditions were considered by calculations in gas phase at the B3LYP/6-311++G** level and in polar medium utilizing PCM methods at the same level of theory. In all cases Me keto forms were found to be more stable and this form should be expected to exist in real systems. Experimental evidence for this statement was found by the IR spectra measured in KBr, polar and nonpolar solvent. The IR spectroscopy was employed to monitor the formation of anion derivative of 6-(propan-2-yl)-3-methyl-morpholine-2,5-dione. The corresponding spectral and structural changes, accompanying the molecule -> anion conversion were studied by IR spectra and DFT calculations. The 6-(propan-2-yl)-3 -methyl-morpholine-2,5-dione showed antimicrobial activity against four of five tested bacterial strains, being the most effective against Escherichia coli. (C) 2012 Elsevier B.V. All rights reserved.