Synthesis of small combinatorial libraries of natural products: identification and quantification of new long-chain 3-methyl-2-alkanones from the root essential oil of Inula helenium L. (Asteraceae).
BACKGROUND
Recently, a potent anti-staphylococcal activity of Inula helenium L. (Asteraceae) root essential oil was reported. Also, bioassay guided fractionation of the oil pointed to eudesmane sesquiterpene lactones and a series of unidentified constituents as the main carriers of the observed activity.


OBJECTIVE
To identify nine new constituents (long-chain 3-methyl-2-alkanones) from a fraction of this root essential oil with a low minimum inhibitory concentration value (0.8 µg/mL) by employing a synthetic methodology that leads to the formation of a small combinatorial library of these compounds.


METHODS
The identity of these constituents was inferred from mass spectral fragmentation patterns and GC retention data. A library of 3-methyl-2-alkanones (C11 -C19 homologous series) was synthesised in three steps starting from methyl acetoacetate and the corresponding alkyl halides. The synthetic library was also screened for in vitro anti-microbial activity.


RESULTS
Gas chromatographic analyses of I. helenium essential oil samples with spiked compounds from the synthesised library corroborated the tentative identifications of the long-chain 3-methyl-2-alkanones. The availability of these anti-microbial compounds from this library made it possible to construct GC/FID calibration curves and determine their content in the plant material: 0.08 - 24.2 mg/100 g of dry roots.


CONCLUSIONS
The small combinatorial library approach enabled the first unequivocal identification of long-chain 3-methyl-2-alkanones as plant secondary metabolites, and, also, allowed determination of not only a single compound and biological properties, but those of a group of structurally related compounds.
Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000, Niš, Serbia.
Niko S
NS
Radulović
Marija S
MS
Denić
Zorica Z
ZZ
Stojanović-Radić
D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D002138:Calibration; D002176:Candida albicans / Q000187:drug effects; D002849:Chromatography, Gas; D038143:Inula / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009822:Oils, Volatile / Q000032:analysis* / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000890:Anti-Infective Agents; D009822:Oils, Volatile; D054852:Small Molecule Libraries
3-methyl-2-alkanones; 3-methyl-2-tetradecanone; Anti-staphylococcal activity; Inula helenium L; root essential oil; small combinatorial library