No abstract

Many natural products of plant or microbial origins are derived from enzymatic dearomative oxygenation of 2‐alkylphenolic precursors into 6‐alkyl‐6‐hydroxycyclohexa‐2,4‐dienones. These so‐called ortho‐quinols cyclodimerize via a remarkably selective bispericyclic Diels–Alder reaction. Whether or not the intervention of catalytic or dirigent proteins is involved during this final step of the biosynthesis of these natural products, this cyclodimerization of ortho‐quinols can be chemically reproduced in the laboratory with the same strict level of site‐specific regioselectivity and stereoselectivity. This unique yet unified process, which finds its rationale in the inherent chemical reactivity of those ortho‐quinols, is illustrated herein by an efficient and bioinspired first chemical synthesis of one of the most structurally complex and synthetically challenging examples of such natural cyclodimers, the bisditerpenoid (+)‐maytenone.

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.

Many natural products of plant or microbial origins are derived from enzymatic dearomative oxygenation of 2‐alkylphenolic precursors into 6‐alkyl‐6‐hydroxycyclohexa‐2,4‐dienones. These so‐called ortho‐quinols cyclodimerize via a remarkably selective bispericyclic Diels–Alder reaction. Whether or not the intervention of catalytic or dirigent proteins is involved during this final step of the biosynthesis of these natural products, this cyclodimerization of ortho‐quinols can be chemically reproduced in the laboratory with the same strict level of site‐specific regioselectivity and stereoselectivity. This unique yet unified process, which finds its rationale in the inherent chemical reactivity of those ortho‐quinols, is illustrated herein by an efficient and bioinspired first chemical synthesis of one of the most structurally complex and synthetically challenging examples of such natural cyclodimers, the bisditerpenoid (+)‐maytenone.

Von der Kreidetafel mit der bispericyclischen Diels‐Alder‐Reaktion von ortho‐Chinolen zum Labor mit dem (+)‐Ferruginol‐Substrat und einem chiralen Bisiodyl‐Reagenz im Kolben: Die so erzeugten ortho‐Chinol‐Diastereomere verbinden sich paarweise zu einem C2‐symmetrischen Übergangszustand, in dem [4+2]‐ und [2+4]‐Prozesse äquivalent sind, wie Laurent Pouységu, Stéphane Quideau et al. im Forschungsartikel auf S. 15094 berichten. Unter hohem Druck führt dieser Übergangszustand zum Produkt, (+)‐Maytenon, hier im Hintergrund dargestellt. Grafik: Jean Ung@SQuideau Lab.

No abstract

From the teaching class with the bispericyclic Diels–Alder reaction of ortho‐quinols drawn on the chalk board to the laboratory with the (+)‐ferruginol substrate and a chiral bisiodyl reagent in the flask: The single ortho‐quinol diastereomer thus produced combines in pairs to reach a C2‐symmetric transition state in which [4+2] and [2+4] processes are equivalent, as described by Laurent Pouységu, Stéphane Quideau, and co‐workers in their Research Article on page 14967. Under high pressure, this transition state leads to the product, the natural (+)‐maytenone, which was first isolated from the plant Maytenus dispermus, here appearing in the background image. Design by Jean Ung@SQuideau Lab.