Cyclic Diarylheptanoids from Corylus avellana Green Leafy Covers: Determination of Their Absolute Configurations and Evaluation of Their Antioxidant and Antimicrobial Activities

Abstract

The methanol extract of the leafy covers of Corylus avellana, source of the Italian PGI (protected geographical indication) product "Nocciola di Giffoni", afforded two new cyclic diarylheptanoids, giffonins T and U (2 and 3), along with two known cyclic diarylheptanoids, a quinic acid, flavonoid-, and citric acid derivatives. The structures of giffonins T and U were determined as highly hydroxylated cyclic diarylheptanoids by 1D and 2D NMR experiments. Their relative configurations were assigned by a combined quantum mechanical/NMR approach, comparing the experimental C/H NMR chemical shift data and the related predicted values. The absolute configurations of carpinontriol B (1) and giffonins T and U (2 and 3) were assigned by comparison of their experimental electronic circular dichroism curves with the TDDFT-predicted curves. The ability of the compounds to inhibit the lipid peroxidation induced by HO and HO/Fe was determined by measuring the concentration of thiobarbituric acid reactive substances. Furthermore, the antimicrobial activity of the methanol extract of leafy covers of C. avellana and of the isolated compounds against the Gram-positive strains Bacillus cereus and Staphylococcus aureus and the Gram-negative strains Escherichia coli and Pseudomonas aeruginosa was evaluated. Carpinontriol B (1) and giffonin U (3) at 40 μg/disk caused the formation of zones of inhibition.

Elucidating the Relative and Absolute Configuration of Organic Compounds by Quantum Mechanical Approaches

“…Another interesting case‐study was related to the elucidation of the relative (and then absolute) stereochemical arrangements of carpinontriol B ( 5 ) and of two new identified diarylheptanoids, namely giffonins T‐U ( 6–7 ) (Figure ) . In this case, apart from the three stereocenters for compounds 5 and 6 and the four stereocenters for 7 , we also faced the problem of the presumed hindered rotation along the o‐disubstituted biaryl axis determining one favored arrangement of the two phenyl moieties thus giving rise to atropisomerism .…”

“…On the other hand, J values are not necessarily described by only dihedral angles, such as the case of the 2 J C‐H values that are particularly interesting when the carbon is linked to electronegative substituent (oxygen, nitrogen, or halogen atoms). During the last few years, the QM/NMR combined approach focused on the prediction and comparison of the different J parameters was employed by us in various studies for clarifying the stereochemical arrangement of different compounds , . However, apart the mere “practical” use of the coupling constants for the stereostructural elucidation of organic compounds, i.e.…”

“…In this scenario, the comparison between experimental and calculated electronic circular dichroism (ECD) spectra represents a powerful method for identifying the most probable enantiomeric form, and several applications of this strategy have been recently reported by us. [14i], [14l], [14m], , We have applied this approach in different studies, generally as last step in a complex pipeline starting with the basic molecular formula identification, moving to the identification of the chemical architecture by applying different experimental procedures (such as 1D‐ and 2D‐NMR experiments), then elucidating the relative configurations by applying the QM/NMR combined approach. The elucidations of the absolute configurational patterns of carpinontriol B ( 5 ) and giffonins T‐U ( 6–7 ) (vide supra) represent an interesting application of this approach .…”

“…[14i], [14l], [14m], , We have applied this approach in different studies, generally as last step in a complex pipeline starting with the basic molecular formula identification, moving to the identification of the chemical architecture by applying different experimental procedures (such as 1D‐ and 2D‐NMR experiments), then elucidating the relative configurations by applying the QM/NMR combined approach. The elucidations of the absolute configurational patterns of carpinontriol B ( 5 ) and giffonins T‐U ( 6–7 ) (vide supra) represent an interesting application of this approach . As above reported (section 2.2), these compounds showed an axis of chirality giving rise to atropisomerism that complicated the relative configuration assignment.…”

Plant Specialized Metabolites in Hazelnut (Corylus avellana) Kernel and Byproducts: An Update on Chemistry, Biological Activity, and Analytical Aspects

“…The kernel, the nut of commerce, is surrounded by a dark brown perisperm and protected by a woody shell [7]. Hazelnuts develop in clusters of 1-12, each separately enclosed in a cup of green leafy cover that encloses about threequarters of the nut [8]. Flowers are produced very early in spring before the leaves and are monoecious, with single-sex catkins; the male catkins are pale yellow and 5-12 cm long, and the female ones are very small and largely concealed in the buds, with only the bright-red, 1-to 3-mm-long styles visible [9].…”