Cyclodextrin-based supramolecular nanogels decorated with mannose for short peptide encapsulation.

Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a straightforward technique to fabricate a novel class of physically cross-linked nanogels via a self-assembly process in water involving α-cyclodextrin and a mannose molecule that was hydrophobically modified using an alkyl chain. The alkyl chain-modified mannose was synthesized in five steps, starting with D-mannose.

Baldwin and Whitehead's Manzamine Alkaloids Biosynthesis Hypothesis Involves a Finely Tuned Reactivity of Acrolein: Automated Extraction of Reactivity Patterns from LC-MS Data.

Inspired by the multicomponent reaction-type scenario involving fatty dialdehydes, a nitrogen source, and acrolein, as a key C unit, put forward by Baldwin and Whitehead to explain the formation of manzamine-type alkaloids, 96 multicomponent reactions were designed, and their analytical readouts were deconvoluted using a herein-provided chemoinformatic workflow. This strategy 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 high-content analysis of multicomponent reactions applied to a natural product biosynthetic scenario.

Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence, T1- and ParaCEST MRI.

Applying a single molecular probe to monitor enzymatic activities in multiple, complementary imaging modalities is highly desirable to ascertain detection and to avoid the complexity associated with the use of agents of different chemical entities. We demonstrate here the versatility of lanthanide (Ln) complexes with respect to their optical and magnetic properties and their potential for enzymatic detection in NIR luminescence, CEST and T1 MR imaging, controlled by the nature of the Ln ion, while using a unique chelator. Based on X-ray structural, photophysical, and solution NMR investigations of a family of Ln DO3A-pyridine model complexes, we could rationalize the luminescence (Eu, Yb), CEST (Yb) and relaxation (Gd) properties and their variations between carbamate and amine derivatives.

Combination of Machine Learning and Empirical Computation for the Structural Validation of Trirosaline, a Natural Trimeric Monoterpene Indole Alkaloid from .

Chemical investigation of the emblematic led to the discovery of trirosaline (), the first example of a tris-ajmalicine-type monoterpene indole alkaloid and the first natural trimeric MIA ever reported from this deeply dug plant species. Its structure was primarily elucidated based on NMR and HRESIMS analyses, and the nature of its unique intermonomeric linkages was firmly confirmed based on a combination of empirical computation and ML--DP4 study. Its absolute configuration was mitigated by comparison of experimental and TDDFT-simulated electronic circular dichroism (ECD) spectra.

Proteolytically Stable Diaza-Peptide Foldamers Mimic Helical Hot Spots of Protein-Protein Interactions and Act as Natural Chaperones.

A novel class of peptidomimetic foldamers based on diaza-peptide units are reported. Circular dichroism, attenuated total reflection -Fourier transform infrared, NMR, and molecular dynamics studies demonstrate that unlike the natural parent nonapeptide, the specific incorporation of one diaza-peptide unit at the N-terminus allows helical folding in water, which is further reinforced by the introduction of a second unit at the C-terminus. The ability of these foldamers to resist proteolysis, to mimic the small helical hot spot of transthyretin-amyloid β (Aβ) cross-interaction, and to decrease pathological Aβ aggregation demonstrates that the introduction of diaza-peptide units is a valid approach for designing mimics or inhibitors of protein-protein interaction and other therapeutic peptidomimetics.

From the Spectroscopic Reassessment of Authentic Alkaloid Samples to the Molecular Networking-Guided Discovery of Criophylline-Related Analogues from .

The molecular network-guided exploration of the alkaloid extract of stems revealed a cluster attributed tentatively to dimeric monoterpene indole alkaloids of the rare criophylline subtype, initiating the dual study reported herein. A patrimonial-themed portion of this work was aimed at performing a spectroscopic reassessment of criophylline (), a monoterpene bisindole alkaloid for which the nature of the inter-monomeric connectivity and configurational assignments have remained dubious. A targeted isolation of the entity annotated as criophylline () was undertaken to strengthen the available analytical evidence.

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.

Ominoxanthone-The First Xanthone Linearly Fused to a γ-Lactone from Bidaud Basidiomata. CASE- and DFT-Based Structure Elucidation.

The UHPLC-HRMS analysis of basidiomata extract revealed that this mushroom accumulated elevated yields of an unreported specialized metabolite. The molecular formula of this unknown compound, CHO, 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 (), 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.

Structure elucidation of an aspidofractinine-type monoterpene indole alkaloid from .

The structure and complete NMR assignments of aspidoreticulofractine, an aspidofractinine -oxide, are reported. Its structure was elucidated based on a combination of spectroscopic techniques including 1D and 2D NMR, high-resolution mass spectrometry, and electronic circular dichroism.

Biodereplication of Antiplasmodial Extracts: Application of the Amazonian Medicinal Plant 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.

Density functional theory-nuclear magnetic resonance-validated full structure elucidation of theionbrunonine C, an unstable N-oxide theionbrunonine from Mostuea brunonis.

The structure elucidation of theionbrunonine C, a thioether-bridged dimeric monoterpene indole alkaloid (MIA), and more generally, one of the very few sulfur-containing MIA, is reported after its isolation from Mostuea brunonis (Gelsemiaceae). This unstable structure had already been targeted for isolation in our former, molecular network-guided, investigation of this plant, but this compound had degraded before sufficient spectroscopic data could have been acquired for a complete structure assignment. With this constraint in mind, the rapid acquisition of nuclear magnetic resonance (NMR) data enabled retrieving sufficient spectroscopic information for full structure elucidation, although from a partial set of spectroscopic information ( H and C NMR; COSY, HSQC, and HMBC).

Pyrrovobasine, hybrid alkylated pyrraline monoterpene indole alkaloid pseudodimer discovered using a combination of mass spectral and NMR-based machine learning annotations.

A new vobasine-tryptamine-based monoterpene indole alkaloid pseudodimer was isolated from the stem bark of . As a minor constituent occurring in a thoroughly investigated plant, this molecule was targeted based on a molecular networking strategy and a rational MS-guided phytochemical investigation led to its isolation. Its structure was formally established based on HRMS, 1D/2D NMR data, and the application of the tool Small Molecule Accurate Recognition Technology (SMART 2.

Voatriafricanines A and B, Trimeric Vobasine-Aspidosperma-Aspidosperma Alkaloids from .

Voatriafricanines A and B ( and ), the first examples of vobasine-aspidosperma-aspidosperma monoterpene trisindole alkaloids, were isolated from the stem barks of , guided by a molecular networking strategy. Their structures, including absolute configurations, were elucidated by spectroscopic methods and ECD calculations. Compounds and possess intramolecular hydrogen bonding, sufficiently robust to transfer homonuclear and heteronuclear magnetizations.

A Reappraisal of the Structure of Lyaline as the First Naturally Occurring Nacycline Monoterpene Indole Alkaloid.

Lyaline () is a monoterpene indole alkaloid that was isolated in 1974 from (Rubiaceae) in our laboratory and has not been reported elsewhere since then. Its structure was proposed on the basis of a very limited set of spectroscopic data (viz., H NMR and EIMS) as a structurally bizarre harman-1,4-dihydropyridine derivative.

Structure elucidation of a new lanostane triterpene from Gabonese Ganoderma orbiforme fruiting bodies.

The structure and complete nuclear magnetic resonance (NMR) assignments of orbifomitellic acid, a novel lanostane triterpene isolated from the fruiting bodies of a Gabonese Ganoderma orbiforme (Polyporaceae), are reported. Within the vast catalogue of lanostanes documented from Ganoderma spp., orbifomitellic acid is the first disclosing a -COOH group at C-4.

Structure Reassignment of Melonine and Quantum-Chemical Calculations-Based Assessment of Biosynthetic Scenarios Leading to Its Revised and Original Structures.

Melonine is a basic monoterpene indole alkaloid (MIA) skeleton from that was reported in 1983. The scarcity of its spectroscopic data questioned the validity of its structure. This prompted us to reisolate this molecule and to revise its structure into an unprecedented MIA scaffold.

Streamlined targeting of Amaryllidaceae alkaloids from the bulbs of Crinum scillifolium using spectrometric and taxonomically-informed scoring metabolite annotations.

Four undescribed alkaloids have been isolated from the bulbs of the previously unstudied Crinum scillifolium. These compounds were targeted following a state-of-the-art molecular networking strategy comprising a dereplication against in silico databases and re-ranking of the candidate structures based on taxonomically informed scoring. The unreported structures span across a variety of Amaryllidaceae alkaloids appendages.

In Silico Anticipation of Metabolic Pathways Extended to Organic Chemistry Reactions: A Case Study with Caffeine Alkaline Hydrolysis and The Origin of Camellimidazoles.

Camellimidazoles A-C were recently reported as natural substances in Keemun black tea. Although a "biosynthetic" route to these intriguing imidazole dimers was proposed from caffeine by the authors in this seminal report, we envisioned that a artefactual scenario, consisting of alkaline hydrolysis of caffeine and spontaneous cascade reactions with a methylene donor such as formaldehyde or methylene chloride, could also have led to their formation. To capture the diversity of molecules obtained under these conditions (i.

Phenylpropane as an Alternative Dearomatizing Unit of Indoles: Discovery of Inaequalisines A and B Using Substructure-Informed Molecular Networking.

Inaequalisines A and B ( and ), the first examples of hybrid alkylated phenylpropane monoterpene indole alkaloids, were isolated from the roots of , guided by the combined use of molecular networking and substructure annotation. Their structures, including absolute configuration, were elucidated by spectroscopic methods and ECD calculations. A possible biosynthetic pathway for and was postulated.

Corynanthean-Epicatechin Flavoalkaloids from .

Epicatechocorynantheines A and B, and epicatechocorynantheidine were isolated from the stem bark of . These molecules were pinpointed, and their isolation streamlined, by a molecular networking strategy. The structural elucidation was unambiguously accomplished from HRMS and 1D/2D NMR data.

Molecular Networking Reveals Serpentinine-Related Bisindole Alkaloids from , a Previously Well-Investigated Species.

Five new monoterpene indole alkaloids (-), including four serpentinine-related bisindoles and one alstonine derivative monomer, have been isolated from the aerial parts of . Their structures were elucidated by analysis of their HRMS and NMR spectroscopic data, and their absolute configurations were deduced from the comparison of experimental and simulated ECD spectra. In addition, two known compounds ( and ), previously undescribed from , have also been purified.

Eumitrins C-E: Structurally diverse xanthone dimers from the vietnamese lichen Usnea baileyi.

Three new xanthone dimers, eumitrins C - E (1-3), along with a new depsidone, 3'-O-demethylcryptostictinolide (4) were isolated from the acetone extract of the whole thallus of the lichen Usnea baileyi collected in Vietnam. Their structures were unambiguously established by spectroscopic analyses (HRESIMS, 1D and 2D NMR), as well as comparison to literature data. The absolute configurations of 1-3 were elucidated through electronic circular dichroism (ECD) analyses.

Impact of the Cultivation Technique on the Production of Secondary Metabolites by TM-237-S5, Isolated from the Sponge .

The fungi TM-237-S5 was isolated from the sponge , collected from the mesophotic coral ecosystem of the Red Sea. The strain was cultivated on a potato dextrose agar (PDA) medium, coupling solid-state fermentation and solid-state extraction (SSF/SSE) with a neutral macroreticular polymeric adsorbent XAD Amberlite resin (AMBERLITE XAD1600N). The SSF/SSE lead to high chemodiversity and productivity compared to classical submerged cultivation.