Biodereplication of antiplasmodial extracts: application of the amazonian medicinal plant piper coruscans kunth

Improved methodological tools to hasten antimalarial drug discovery remain of interest, especially when considering natural products as a source of drug candidates. We propose a biodereplication method combining the classical dereplication approach with the early detection of potential antiplasmodial compounds in crude extracts. Heme binding is used as a surrogate of the antiplasmodial activity and is monitored by mass spectrometry in a biomimetic assay. Molecular networking and automated annotation of targeted mass through data mining were followed by mass-guided compound isolation by taking advantage of the versatility and finely tunable selectivity offered by centrifugal partition chromatography. This biodereplication workflow was applied to an ethanolic extract of the Amazonian medicinal plant Piper coruscans Kunth (Piperaceae) showing an IC50 of 1.36 ug/mL on the 3D7 Plasmodium falciparum strain. It resulted in the isolation of twelve compounds designated as potential antiplasmodial compounds by the biodereplication workflow. Two chalcones, aurentiacin (1) and cardamonin (3), with IC50 values of 2.25 and 5.5 uM, respectively, can be considered to bear the antiplasmodial activity of the extract, with the latter not relying on a heme-binding mechanism. This biodereplication method constitutes a rapid, efficient, and robust technique to identify potential antimalarial compounds in complex extracts such as plant extracts

Clarifying the Configuration of Pandamine by an Extensive Spectroscopic Reinvestigation of the Authentic 1964 Sample

Since its partial configurational assignment in 1964, pandamine has not been isolated or obtained by total synthesis. For decades, different works representing the structure of pandamine for illustrative purposes have lent different configurations to this molecule, causing tenacious confusion about the structure of this ansapeptide. A comprehensive spectroscopic analysis of the authentic pandamine sample led to the complete and unambiguous assignment of its configuration, 59 years after its isolation. In addition to ascertaining and completing the initial structural deductions by a state-of-the-art set of analytical techniques, the purpose of this study is also to clarify the literature in a context in which various erroneous structures have been attributed to pandamine for half a century. While fully in agreement with Goutarel’s conclusions, the specific example of pandamine should serve as a cautionary tale to any chemist interested in natural products, encouraging access to initial structural assignments rather than relying solely on subsequent, possibly erroneous, structure depictions of a natural product.info:eu-repo/semantics/publishe

Baldwin and Whitehead’s Manzamine Alkaloids Biosynthesis Hy-pothesis Involves a Finely Tuned Reactivity of C3 Unit: a High-Throughput Experimentation Approach

A rapid analysis of mass spectrometry data generated from 96 multicomponent reactions using a herein-provided chemoinformatic workflow, have pinpointed relevant conditions tuning the reactivity of acrolein to fulfill Baldwin and Whitehead’s manzamine alkaloids biosynthetic hypothesis. This strategy can become part of a general method for the analysis of information-rich high-throughput experiments of multicomponent reactions applied to natural product biosynthetic scenari

Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for Enantioselective Total Synthesis of Mavacuran Alkaloids

International audienceWe report the enantioselective total syntheses of mavacurans alkaloids, (+)-taberdivarine H, (+)-16-hydoxymethylpleiocarpamine, (+)-16-epi-pleiocarpamine, and their postulated biosynthetic precursor 16-formyl-pleiocarpamine. This family of monoterpene indole alkaloids is a target of choice since some of its members are subunits of intricate bisindole alkaloids such as bipleiophylline. Inspired by the biosynthetic hypothesis, we explored an oxidative coupling approach from the geissoschizine framework to form the N1-C16 bond. Quaternization of the aliphatic nitrogen was key to achieve the oxidative coupling induced by KHMDS/I2 since it hides the nucleophilicity of the aliphatic nitrogen and locks the required cis conformation. Scheme 3. Synthesis of 16-deformyl-geissoschizine (22), geissoschizine (1) and geissoschizine malonate 23 according to our previous work. With a straightforward access to the geissoschizine framework, we were in position to evaluate our hypothesis of oxidative cyclization after quaternization of the aliphatic nitrogen N4. A

Insights into the Biosynthesis of Cyclic Guanidine Alkaloids from Crambeidae Marine Sponges

International audienceAmong the outstanding chemical diversity found in marine sponges, cyclic guanidine alkaloids, present in species of the family Crambeidae, are particularly attractive, not only because of their unique chemical features, but also due to a broad range of biological activities. Despite a growing interest in these natural products as therapeutic agents, their metabolic pathway has not been experimentally investigated. Ex situ feeding experiments using radiolabeled precursors performed on the Mediterranean sponge Crambe crambe suggest arginine and fatty acids as precursors in the metabolic pathway of crambescins. A subsequent bio-inspired approach supported the change of paradigm in the metabolic pathway of cyclic guanidine alkaloids. A large part of the chemical diversity of this family would therefore originate from a tethered Biginelli-like reaction between C-2/C-3 activated fatty acids and a central guanidinylated pyrrolinium

Innovative Approach to Sustainable Marine Invertebrate Chemistry and a Scale-Up Technology for Open Marine Ecosystems

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Ominoxanthone—The First Xanthone Linearly Fused to a γ-Lactone from <i>Cortinarius ominosus</i> Bidaud Basidiomata. CASE- and DFT-Based Structure Elucidation

The UHPLC–HRMS analysis of Cortinarius ominosus basidiomata extract revealed that this mushroom accumulated elevated yields of an unreported specialized metabolite. The molecular formula of this unknown compound, C17H10O8, indicated that a challenging structure elucidation lay ahead, owing to its critically low H/C atom ratio. The structure of this new isolate, namely ominoxanthone (1), could not be solved from the interpretation of the usual set of 1D/2D NMR data that conveyed too limited information to afford a single, unambiguous structure. To remedy this, a Computer-Assisted Structure Elucidation (CASE) workflow was used to rank the different possible structure candidates consistent with our scarce spectroscopic data. DFT-based chemical shift calculations on a limited set of top-ranked structures further ascertained the determined structure for ominoxanthone. Although the determined scaffold of ominoxanthone is unprecedented as a natural product, a plausible biosynthetic scenario involving a precursor known from cortinariaceous sources and classical biogenetic reactions could be proposed

Caffeine Alkaline Hydrolysis and in Silico Anticipation Reveal the Origin of Camellimidazoles

- Context. Camellimidazoles A–C were recently reported as new natural substances arising from what was described as new caffeine degradation pathway in Keemun black tea. - Discoveries. Under alkaline hydrolysis conditions followed by spontaneous cascade reactions with formaldehyde or dichloromethane (as the key methylene group providers), we were able to achieve the synthesis of camellimidazoles B and C. A MetWork-based pipeline was also implemented highlighting a wealth of structurally diverse compounds formed in the course of the reaction and streamlining the isolation of the newly described camellimidazoles D-F, subsequently confirmed as anticipated in silico upon extensive spectroscopic analyses. Besides demonstrating the artefactual origin of camellimidazoles, the current investigation emphasizes the fitness of MetWork-tagging to illuminate the chemical diversity associated with seemingly simple reactive conditions.- Methods. Organic synthesis, phytochemical analysis, in silico anticipation, molecular networking dereplication</div