Palladium-Catalyzed Direct Arylation of Selenophene

An efficient and convenient method was developed for the regioselective formation of 2-aryl- or 2,5-diarylselenophenes via a palladium-catalyzed direct arylation. This protocol is suitable for a wide range of aryl halides containing different functional groups. The 2-arylated substrates can undergo an additional regioselective direct arylation event furnishing symmetrical or unsymmetrical 2,5-diaryl selenophenes in good yield. Competition experiments and the role of the acid additive are in agreement with a concerted metalation deprotonation (CMD) pathway

Total Synthesis of Epothilone D: The Nerol/Macroaldolization Approach

A highly convergent and stereocontrolled synthesis of epothilone D (<b>4</b>) is reported. Key features are a cheap and <i>Z</i>-selective synthesis of the northern half based on nerol and acetoacetate and chromium­(II)-mediated Reformatsky reactions as a powerful tool for chemoselective asymmetric carbon–carbon bond formations, including an unusual stereospecific macroaldolization

Profiling the chemical content of <i>Ficus lyrata</i> extracts <i>via</i> UPLC-PDA-qTOF-MS and chemometrics

<div><p>This study attempts to elucidate the secondary metabolite profiles of <i>Ficus lyrata</i> leaves and fruits grown in Egypt. Non-targeted metabolite profiling <i>via</i> ultra performance liquid chromatography (UPLC)-qTOF-MS was used to identify various chemical classes in <i>F. lyrata</i> fruits and leaves (i.e. flavonoids, phenolic acids and fatty acids) analysed by chemometrics. A total of 72 metabolites were evaluated <i>via</i> a UPLC-qTOF-MS-based metabolomic study. Seventeen flavonoids were characterised and tentatively identified with the main constituents being catechins/procyanidins, <i>O</i>- and <i>C</i>-linked flavonoid glycosides. The major procyanidins were dimers and trimers comprising (epi)catechin and (epi)afzelechin units, whereas the predominant flavones were <i>C</i>-glycosides of luteolin and apigenin. Aside from these major flavonoid classes, a group of benzoic acids, caffeoylquinic acids, fatty acid and sphingolipids were also annotated. This study provides the most complete map for polyphenol distribution in <i>F. lyrata</i> leaves and fruits and the basis for future investigation of its fruits nutritional value or possible nutraceutical uses.</p></div

Peptide Macrocyclization Assisted by Traceless Turn Inducers Derived from Ugi Peptide Ligation with Cleavable and Resin-Linked Amines

A multicomponent approach enabling the installation of turn-inducing moieties that facilitate the macrocyclization of short and medium-size oligopeptides is described. The strategy comprises the Ugi ligation of peptide carboxylic acids and isocyanopeptides in the presence of aldehydes and acid or photolabile amines followed by cyclization and cleavage of the backbone <i>N</i>-substituents to render canonical cyclopeptides. Implementing the approach on solid phase with the use of Rink amide resins led to a new class of backbone amide linker strategy

Solution- and Solid-Phase Macrocyclization of Peptides by the Ugi–Smiles Multicomponent Reaction: Synthesis of <i>N</i>‑Aryl-Bridged Cyclic Lipopeptides

A new multicomponent methodology for the solution- and solid-phase macrocyclization of peptides is described. The approach comprises the utilization of the Ugi–Smiles reaction for the cyclization of 3-nitrotyrosine-containing peptides either by the N-terminus or the lysine side-chain amino groups. Both the on-resin and solution cyclizations took place with good to excellent efficiency in the presence of an aldehyde and a lipidic isocyanide, while the use of paraformaldehyde required an aminocatalysis-mediated imine formation prior to the on-resin Ugi–Smiles ring closure. The introduction of a turn motif in the peptide sequence facilitated the cyclization step, shortened the reaction time, and delivered crude products with >90% purity. This powerful method provided a variety of structurally novel <i>N</i>-aryl-bridged cyclic lipopeptides occurring as single atropisomers

Gas Chromatography/Mass Spectrometry-Based Metabolite Profiling of Nutrients and Antinutrients in Eight Lens and Lupinus Seeds (Fabaceae)

Lens culinaris and several Lupinus species are two legumes regarded as potential protein resources aside from their richness in phytochemicals. Consequently, characterization of their metabolite composition seems warranted to be considered as a sustainable commercial functional food. This study presents a discriminatory holistic approach for metabolite profiling in accessions of four lentil cultivars and four Lupinus species via gas chromatography/mass spectrometry. A total of 107 metabolites were identified, encompassing organic and amino acids, sugars, and sterols, along with antinutrients, <i>viz</i>., alkaloids and sugar phosphates. Among the examined specimens, four nutritionally valuable accessions ought to be prioritized for future breeding to include Lupinus hispanicus, enriched in organic (<i>ca.</i> 11.7%) and amino acids (<i>ca.</i> 5%), and Lupinus angustifolius, rich in sucrose (<i>ca.</i> 40%), along with two dark-colored lentil cultivars ‘verte du Puy’ and ‘Black Beluga’ enriched in peptides. Antinutrient chemicals were observed in Lupinus polyphyllus, owing to its high alkaloid content. Several species-specific markers were also revealed using multivariate data analyses

Applications of Convertible Isonitriles in the Ligation and Macrocyclization of Multicomponent Reaction-Derived Peptides and Depsipeptides

Peptide ligation and macrocyclization are among the most relevant approaches in the field of peptide chemistry. Whereas a variety of strategies relying on coupling reagents and native chemical ligation are available, there is a continuous need for efficient peptide ligation and cyclization methods. Herein we report on the utilization of convertible isonitriles as effective synthetic tools for the ligation and macrocyclization of peptides arising from isocyanide-based multicomponent reactions. The strategy relies on the use of convertible isonitrilesderived from Fukuyama aminesand peptide carboxylic acids in Ugi and Passerini reactions to afford <i>N</i>-alkylated peptides and depsipeptides, respectively, followed by conversion of the <i>C</i>-terminal amide onto either <i>N</i>-peptidoacyl indoles or pyrroles. Such activated peptides proved efficient in the ligation to peptidic, lipidic and fluorescently labeled amines and in macrocyclization protocols. As a result, a wide set of <i>N</i>-substituted peptides (with methyl, glycosyl and amino acids as <i>N</i>-substituents), cyclic <i>N</i>-methylated peptides and a depsipeptide were produced in good yields using conditions that involve either classical heating or microwave irradiation. This report improves the repertoire of peptide covalent modification methods by exploiting the synthetic potential of multicomponent reactions and convertible isonitriles

Comparative Metabolomics Approach Detects Stress-Specific Responses during Coral Bleaching in Soft Corals

Chronic exposure to ocean acidification and elevated sea-surface temperatures pose significant stress to marine ecosystems. This in turn necessitates costly acclimation responses in corals in both the symbiont and host, with a reorganization of cell metabolism and structure. A large-scale untargeted metabolomics approach comprising gas chromatography mass spectrometry (GC–MS) and ultraperformance liquid chromatography coupled to high resolution mass spectrometry (UPLC–MS) was applied to profile the metabolite composition of the soft coral <i>Sarcophyton ehrenbergi</i> and its dinoflagellate symbiont. Metabolite profiling compared ambient conditions with response to simulated climate change stressors and with the sister species, <i>S. glaucum</i>. Among ∼300 monitored metabolites, 13 metabolites were modulated. Incubation experiments providing four selected upregulated metabolites (alanine, GABA, nicotinic acid, and proline) in the culturing water failed to subside the bleaching response at temperature-induced stress, despite their known ability to mitigate heat stress in plants or animals. Thus, the results hint to metabolite accumulation (marker) during heat stress. This study provides the first detailed map of metabolic pathways transition in corals in response to different environmental stresses, accounting for the superior thermal tolerance of <i>S. ehrenbergi</i> versus <i>S. glaucum</i>, which can ultimately help maintain a viable symbiosis and mitigate against coral bleaching

Soft Corals Biodiversity in the Egyptian Red Sea: A Comparative MS and NMR Metabolomics Approach of Wild and Aquarium Grown Species

Marine life has developed unique metabolic and physiologic capabilities and advanced symbiotic relationships to survive in the varied and complex marine ecosystems. Herein, metabolite composition of the soft coral genus <i>Sarcophyton</i> was profiled with respect to its species and different habitats along the coastal Egyptian Red Sea via ¹H NMR and ultra performance liquid chromatography-mass spectrometry (UPLC–MS) large-scale metabolomics analyses. The current study extends the application of comparative secondary metabolite profiling from plants to corals revealing for metabolite compositional differences among its species via a comparative MS and NMR approach. This was applied for the first time to investigate the metabolism of 16 <i>Sarcophyton</i> species in the context of their genetic diversity or growth habitat. Under optimized conditions, we were able to simultaneously identify 120 metabolites including 65 diterpenes, 8 sesquiterpenes, 18 sterols, and 15 oxylipids. Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS) were used to define both similarities and differences among samples. For a compound based classification of coral species, UPLC–MS was found to be more effective than NMR. The main differentiations emanate from cembranoids and oxylipids. The specific metabolites that contribute to discrimination between soft corals of <i>S. ehrenbergi</i> from the three different growing habitats also belonged to cembrane type diterpenes, with aquarium <i>S. ehrenbergi</i> corals being less enriched in cembranoids compared to sea corals. PCA using either NMR or UPLC–MS data sets was found equally effective in predicting the species origin of unknown <i>Sarcophyton</i>. Cyclopropane containing sterols observed in abundance in corals may act as cellular membrane protectant against the action of coral toxins, that is, cembranoids