Denis Deffieux

Resveratrol Still Has Something To Say about Aging

A votre Santé! The mechanism by which resveratrol, a hydroxystilbenoid polyphenol found in grapes and present in wine, exerts antiaging metabolic benefits has been uncovered. Chung and co-workers have found that it works by inhibiting cAMP phosphodiesterases, thus triggering a signaling cascade that leads to the possible activation of the mammalian enzyme sirtuinu20051.

Gallotannins and Tannic Acid: First Chemical Syntheses and In Vitro Inhibitory Activity on Alzheimer’s Amyloid β‐Peptide Aggregation

The screening of natural products in the search for new lead compounds against Alzheimers disease has unveiled several plant polyphenols that are capable of inhibiting the formation of toxic β-amyloid fibrils. Gallic acid based gallotannins are among these polyphenols, but their antifibrillogenic activity has thus far been examined using tannic acid, a commercial mixture of gallotannins and other galloylated glucopyranoses. The first total syntheses of two true gallotannins, a hexagalloylglucopyranose and a decagalloylated compound whose structure is commonly used to depict tannic acid, are now described. These depsidic gallotannins and simpler galloylated glucose derivatives all inhibit amyloid β-peptide (Aβ) aggregation inu2005vitro, and monogalloylated α-glucogallin and a natural β-hexagalloylglucose are shown to be the strongest inhibitors.

Phenol Dearomatization with Hypervalent Iodine Reagents.

This chapter highlights recent developments in phenol dearomatization using organoiodane reagents and a selection of applications in natural product synthesis.

Bioinspired Total Synthesis of (−)-Vescalin: A Nonahydroxytriphenoylated C-Glucosidic Ellagitannin

The first total synthesis of the 2,3,5-O-(S,R)-nonahydroxytriphenoylated (NHTP) C-glucosidic ellagitannin (-)-vescalin was accomplished through a series of transformations mimicking the sequence of events leading to its biogenesis. The key steps of this synthesis encompass a Wittig-mediated ring opening of a glucopyranosic hemiacetal, a C-glucosidation event through a phenolic aldol-type reaction, and a Wynberg-Feringa-Yamada-type oxidative phenolic coupling, which forged the NHTP unit of (-)-vescalin.

Rapid Screening of Ellagitannins in Natural Sources via Targeted Reporter Ion Triggered Tandem Mass Spectrometry

Complex biomolecules present in their natural sources have been difficult to analyze using traditional analytical approaches. Ultrahigh-performance liquid chromatography (UHPLC-MS/MS) methods have the potential to enhance the discovery of a less well characterized and challenging class of biomolecules in plants, the ellagitannins. We present an approach that allows for the screening of ellagitannins by employing higher energy collision dissociation (HCD) to generate reporter ions for classification and collision-induced dissociation (CID) to generate unique fragmentation spectra for isomeric variants of previously unreported species. Ellagitannin anions efficiently form three characteristic reporter ions after HCD fragmentation that allows for the classification of unknown precursors that we call targeted reporter ion triggering (TRT). We demonstrate how a tandem HCD-CID experiment might be used to screen natural sources using UHPLC-MS/MS by application of 22 method conditions from which an optimized data-dependent acquisition (DDA) emerged. The method was verified not to yield false-positive results in complex plant matrices. We were able to identify 154 non-isomeric ellagitannins from strawberry leaves, which is 17 times higher than previously reported in the same matrix. The systematic inclusion of CID spectra for isomers of each species classified as an ellagitannin has never been possible before the development of this approach.

Anti-Herpes Simplex Virus Type 1 Activity of Specially Selected Groups of Tannins

Anti-herpes simplex virus (HSV-1) activity of 9 ellagitannins, including 6 natural compounds (castalin, vescalin, acutissimin A, epiacutissimins A and B, mongolicain) and 3 vescalagin synthetic derivatives (VgSBuSH, VgSOctSH, VgOMe), and 13 gallotannin-type compounds [Gal-01A, Gal-01B, Gal-02A, Gal-02B, Gal-03M, Gal-04A, Gal-04B, Gal-05M, Gal-07, Gal-08, Gal-09, Gal-11M (tannic acid), as well as Gal-12 (gallic acid), Gal-13 and Gal-14 (ellagic acid)] were examined in MDBK monolayer cell culture. Their antiviral activity was determined by the cytopathic effect (CPE) inhibition test and their cytotoxicity was evaluated through the neutral red uptake assay. In general, the series of ellagitannins showed a significantly stronger activity against HSV-1 replication than that of the gallotannins. Six of the tested ellagitannins manifested a well-pronounced activity: epiacutissimin B (selectivity index, SI>60.6), epiacutissimin A (SI>55.5), acutissimin A (SI>34.8), mongolicain (SI>32.5), VgSBuSH (SI>24.6) and VgOMe (SI>22.0). Four gallotannin-type compounds inhibited the replication of HSV-1 at a lower but still significant extent: Gal-04B (SI>35.7), Gal-04A (SI>28.5), Gal-11M (tannic acid) (SI>25) and Gal-05M (SI=15.6).