Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold.

The synthesis of tripeptides incorporating new fluorinated heterocyclic hydrazino acids, based on the tetrahydropyridazine scaffold is described. Starting from simple fluorinated hydrazones, these non-proteinogenic cyclic β-amino acids were easily prepared by a zinc-catalyzed aza-Barbier reaction followed by an intramolecular Michael addition. Preliminary conformational studies on tripeptides including this scaffold in the central position show an extended conformation in solution (NMR) and in the solid state (X-ray).

Correction: Mass-tagged aminated probes for rapid discovery of azaphilic natural products in fungal crude extracts.

Correction for 'Mass-tagged aminated probes for rapid discovery of azaphilic natural products in fungal crude extracts' by Victor Flon , , 2024, https://doi.org/10.1039/D4CC05122J.

Mass-tagged aminated probes for rapid discovery of azaphilic natural products in fungal crude extracts.

Reactivity-based screening (RBS) was used to screen fungal crude extracts for the presence of new azaphilic natural products. A probe composed of a nucleophilic primary amine and an isotopic mass tag was designed for its reactivity towards azaphilic compounds. Addition of the probe to crude extracts of fungal complexes, together with analytical tools for dereplication such as haloseeker and molecular networking, allowed easy detection of azaphilic compounds.

A solvent-free and catalyst-free reaction of -aminobenzophenone with aryl isothiocyanates: expedient access to congested 4-phenyl-4-hydroxyquinazolin-2-thione derivatives.

An efficient method to construct 4-phenyl-4-hydroxyquinazolin-2-thiones 3 solvent-free and catalyst-free addition of -aminobenzophenone 1 with aryl isothiocyanates 2 under thermal conditions has been developed, providing new congested 4-phenyl-4-hydroxyquinazolin-2-thiones 3 in practically quantitative yields simple purification by filtration/recrystallization. Extension of these conditions to -aminoacetophenone 4 in place of -aminobenzophenone 1 led to 4-methylenequinazoline-thione 5 as a result of a subsequent dehydration reaction.

Room temperature dithiocarbamation of 2-tetralones with elemental sulfur and isothiocyanates S/R-NCS: atom-efficient access to 4-hydroxythiazolidine-2-thiones.

2-Tetralones were found to undergo dithiocarbamation with elemental sulfur and isothiocyanates S/R-NCS in the presence of -methylpiperidine as a base catalyst under solvent-free conditions. The reaction could proceed quickly at room temperature to provide convenient access to substituted 4-hydroxythiazolidine-2-thiones with complete atom efficiency. The adducts could be easily dehydrated in neat TFA to give thiazole-2-thiones.

Redox condensation of -halonitrobenzenes, sulfur and isothiocyanates: access to 2-aminobenzothiazoles.

The elemental sulfur and isothiocyanate (S/RNCS) couple was found to undergo redox condensation with -halonitrobenzenes in the presence of -methylpiperidine as a base in -methylpyrrolidin-2-one to provide step- and redox-economical access to 2-aminobenzothiazoles. Alternatively, dithiocarbamate salts generated from addition of amines and CS could be used in place of the S/RNCS couple.

Tuning the Thermal Stability of Tetra-o-chloroazobenzene Derivatives by Transforming Push-Pull to Push-Push Systems.

Molecular photoswitches provide interesting tools to reversibly control various biological functions with light. Thanks to its small size and easy introduction into the biomolecules, azobenzene derivatives have been widely employed in the field of photopharmacology. All visible-light switchable azobenzenes with controllable thermostability are highly demanded.

Brønsted Acid Catalyzed Asymmetric Synthesis of Cyclopentenones with C4-Quaternary Centers Starting from Vinyl Sulfoxides and Allenyl Ketones or Allenoates.

Starting with chiral vinyl sulfoxides and allenyl ketones or allenoates, a triflic acid-catalyzed asymmetric [3,3]-sigmatropic rearrangement of sulfoniums is reported to have a direct access to highly functionalized C4-chiral cyclopentenones (19 examples, up to 85% yield and >95% enantiomeric excesses). In addition to the use of these chiral compounds as key building blocks in organic synthesis, the antiproliferative activities of sulfoxide substrates and the corresponding cyclopentenones were evaluated, and promising cytotoxicity against the HL-60 human tumor cell line was found.

Synthesis of Halogenated Dibenzo[1,2,6]triazonines and Late-Stage Functionalization of the Triazonine Ring.

Dibenzotriazonine represent a new class of nine-membered cyclic azobenzenes with a nitrogen atom embedded in the bridging chain. To enable future applications of this photoactive backbone, we propose in this study the synthesis of mono- and dihalogenated triazonines, that allow the late-stage introduction of different functionalized aryl groups and heteroatoms (N, O, and P) via palladium-catalyzed reactions. Indeed, different diphenylphosphoryl-triazonines were synthesized with functional groups such as aniline or phenol.

Sulfur-Promoted Access to 3-Arylquinoxalin-2-ones by Oxidative Coupling of -Phenylenediamines with Arylacetates.

We disclose the synthesis of 3-arylquinoxalin-2-ones from -phenylenediamines and readily available arylacetates. The method harnesses the selective oxidative property of elemental sulfur in the presence of amine base catalyst and DMSO. The reactions are operationally simple and tolerate a wide range of functional groups.

Stimuli-Induced Fluorescence Switching in Azine-Containing Fluorophores Displaying Resonance-Stabilized ESIPT Emission.

This article reports the synthesis, along with structural and photophysical characterization of 2-(2'-hydroxyphenyl)benzazole derivatives functionalized with various azaheterocycles (pyridine, pyrimidine, terpyridine). These compounds show dual-state emission properties, that is intense fluorescence both in solution and in the solid-state with a range of fluorescent color going from blue to orange. Moreover, the nature of their excited state can be tuned by the presence of external stimuli such as protons or metal cations.

Leveraging -tosylhydrazones as diazo surrogates for efficient access to pyrazolo-[1,5-]quinazolinone derivatives.

We developed a transition metal-free methodology for the construction of pyrazoloquinazolinone derivatives. The strategy involves a one-pot reaction wherein the -tosylhydrazone and its corresponding diazo derivative are generated , followed by an intramolecular 1,3-dipolar cycloaddition-ring expansion to provide the pyrazolo-[1,5-]quinazolinone motif. This approach enables straightforward access to a diverse range of highly functionalized N-heterocyclic compounds in good yields (up to 92%).

Photocatalytic Asymmetric Acyl Radical Truce-Smiles Rearrangement for the Synthesis of Enantioenriched α-Aryl Amides.

The radical Truce-Smiles rearrangement is a straightforward strategy for incorporating aryl groups into organic molecules for which asymmetric processes remains rare. By employing a readily available and non-expensive chiral auxiliary, we developed a highly efficient asymmetric photocatalytic acyl and alkyl radical Truce-Smiles rearrangement of α-substituted acrylamides using tetrabutylammonium decatungstate (TBADT) as a hydrogen atom-transfer photocatalyst, along with aldehydes or C-H containing precursors. The rearranged products exhibited excellent diastereoselectivities (7 : 1 to >98 : 2 d.

Chemical Investigation of the Calcareous Marine Sponge , Clathridine-A Related Derivatives Isolation, Synthesis and Osteogenic Activity.

As a result of screening a panel of marine organisms to identify lead molecules for the stimulation of endochondral bone formation, the calcareous sponge was identified to exhibit significant activity during endochondral differentiation. On further molecular networking analysis, dereplication and chemical fractionation yielded the known clathridine A-related metabolites and the homodimeric complex (clathridine A) Zn (), together with the new unstable heterodimeric complex (clathridine A-clathridimine)Zn (). With the presence of the zinc complexes annotated through the LC-MS analysis of the crude extract changing due to the instability of some metabolites and complexes constituting the mixture, we combined the isolation of the predicted molecules with their synthesis in order to confirm their structure and to understand their reactivity.

Experimental and theoretical comprehension of ESIPT fluorophores based on a 2-(2'-hydroxyphenyl)-3,3'-dimethylindole (HDMI) scaffold.

Excited-State Intramolecular Proton Transfer (ESIPT) emission is associated with intense single or multiple fluorescence in the solid-state, along with enhanced photostability and sensitivity to the close environment. As a result, ESIPT probes are attractive candidates for ratiometric sensing of a variety of substrates. A new family of ESIPT fluorophores is described herein, inspired by the well-known 2-(2'hydroxyphenyl)benzazole (HBX) organic scaffold.

Base- and sulfur-promoted oxidative lactonization of chalcone-acetate Michael adducts: access to pyran-2-ones.

A cost-effective, practical, straightforward and scalable synthesis of α-pyrones base- and sulfur-promoted annulation of phenylacetates and chalcones is reported. Generated from the starting components by using dbu as a base catalyst, the Michael adducts underwent a smooth oxidative cyclization into 3,4,6-triaryl-2-pyranones upon heating with DABCO and sulfur in DMSO. Extension to malonate in place of phenylacetates led to 4,6-diaryl-2-pyranone-2-carboxylates.

Synthesis and Characterization of a [1,2,6]Diazaphosphonine Oxide: An Example of a Photoswitchable Phosphorus-Containing Cyclic Azobenzene.

We report herein the synthesis and characterization of a phosphorus-containing cyclic azobenzene as a new photoswitchable scaffold. This backbone reveals high bidirectional photoswitching yields and high thermal stability for both isomers, with > 90 days at 60 °C. Both - and -isomers have been characterized by UV-vis spectroscopy and X-ray crystallography.

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.

Crystal structure of poly[hexa-μ-bro-mido-bis{2-[1-(py-ri-din-2-yl)ethyl-idene-amino]ethanol-ato}tetracopper(II)].

The reaction of the Schiff base 2-[1-(pyridin-2-yl)ethyl-idene-amino]-ethanol (H), which is formed by reaction of 2-amino-ethanol and 2-acetyl-pyridine with CuBr in ethanol results in the isolation of the new polymeric complex poly[hexa-μ-bromido-bis-{2-[1-(pyridin-2-yl)ethyl-idene-amino]-ethano-lato}tetra-copper(II)], [CuBr(CHNO)] or [CuBr ]. The asymmetric unit of the crystal structure of the polymeric [CuBr ] complex is composed by four copper (II) cations, two monodeprotonated mol-ecules of the ligand, and six bromide anions, which act as bridges. The ligand mol-ecules act in a tridentate fashion through their azomethine nitro-gen atoms, their pyridine nitro-gen atoms, and their alcoholate O atoms.

Sodium sulfide-promoted regiodefined redox condensation of -nitroanilines with aryl ketones to benzo[]phenazines and quinoxalines.

Inexpensive sodium sulfide trihydrate was found to promote unprecedented 6e-regio-predefined redox condensation of -nitroanilines with α-tetralones to benzo[]phenazines. The method was also successfully extended to acetophenones and higher homologs as reducing partners to provide 2-phenylquinoxalines. Compared to traditional approaches toward benzo[]phenazine and quinoxaline cores starting with -phenylenediamines, the present strategy could afford these heterocycles with well-defined regiochemistry based on the structure of starting -nitroanilines.

Enantioselective and Regiodivergent Synthesis of Dihydro-1,2-oxazines from Triene-Carbamates via Chiral Phosphoric Acid-Catalysis.

Conjugated trienes are fascinating building blocks for the rapid construction of complex polycyclic compounds. However, limited success has been achieved due to the challenging regioselectivity control. Herein, we report an enantio- and diastereoselective process allowing to regioselectively control the functionalization of H-triene-carbamates.

Sulfur- and Amine- Promoted Multielectron Autoredox Transformation of Nitromethane: Multicomponent Access to Thiourea Derivatives.

Thiourea derivatives are in-demand motifs in organic synthesis, medicinal chemistry and material science, yet redox methods for the synthesis that start from safe, simple, inexpensive and readily available feedstocks are scarce. In this article, we disclose the synthesis of these motifs using elemental sulfur and nitromethane as the starting materials. The method harnesses the multi-electron auto-redox property of nitromethane in the presence of sulfur and amines, delivering thiourea products without any added oxidant or reductant.

Functional and structural insights into the multi-step activation and catalytic mechanism of bacterial ExoY nucleotidyl cyclase toxins bound to actin-profilin.

ExoY virulence factors are members of a family of bacterial nucleotidyl cyclases (NCs) that are activated by specific eukaryotic cofactors and overproduce cyclic purine and pyrimidine nucleotides in host cells. ExoYs act as actin-activated NC toxins. Here, we explore the Vibrio nigripulchritudo Multifunctional-Autoprocessing Repeats-in-ToXin (MARTX) ExoY effector domain (Vn-ExoY) as a model for ExoY-type members that interact with monomeric (G-actin) instead of filamentous (F-actin) actin.