Thiosuccinimide enabled S-N bond formation to access N-sulfenylated sulfonamide derivatives with synthetic diversity.

A thiosuccinimide enabled S-N cross-coupling strategy has been established for the intermolecular N-sulfenylation of clinically approved sulfa drugs under additive-free conditions. This approach features simple operation, high chemoselectivity for sulfenylating the phenylamino group of sulfonamides, wide substrate scope, and easy scale production, affording N-sulfenylated products in moderate to excellent yields (up to 90%). In addition, we also found that this transformation can be realized in a one-pot manner by employing readily available thiols as starting materials, and the obtained sulfonamide derivatives are capable of various late-stage functionalizations, including oxidation, arylation, benzylation, and methylation.

O1-conotoxin Tx6.7 cloned from the genomic DNA of Conus textile that inhibits calcium currents.

Background: Conotoxins exhibit great potential as neuropharmacology tools and therapeutic candidates due to their high affinity and specificity for ion channels, neurotransmitter receptors or transporters. The traditional methods to discover new conotoxins are peptide purification from the crude venom or gene amplification from the venom duct. Methods: In this study, a novel O1 superfamily conotoxin Tx6.7 was directly cloned from the genomic DNA of Conus textile using primers corresponding to the conserved intronic sequence and 3' UTR elements. The mature peptide of Tx6.7 (DCHERWDWCPASLLGVIYCCEGLICFIAFCI) was synthesized by solid-phase chemical synthesis and confirmed by mass spectrometry. Results: Patch clamp experiments on rat DRG neurons showed that Tx6.7 inhibited peak calcium currents by 59.29 ± 2.34% and peak potassium currents by 22.33 ± 7.81%. In addition, patch clamp on the ion channel subtypes showed that 10 µM Tx6.7 inhibited 56.61 ± 3.20% of the hCaV1.2 currents, 24.67 ± 0.91% of the hCaV2.2 currents and 7.30 ± 3.38% of the hNaV1.8 currents. Tx6.7 had no significant toxicity to ND7/23 cells and increased the pain threshold from 0.5 to 4 hours in the mouse hot plate assay. Conclusion: Our results suggested that direct cloning of conotoxin sequences from the genomic DNA of cone snails would be an alternative approach to obtaining novel conotoxins. Tx6.7 could be used as a probe tool for ion channel research or a therapeutic candidate for novel drug development.

Two new phenolic glucosides from marine-derived fungus Aspergillus sp.

Two new phenolic glucosides, including a new O-glycoside (1) and a new C-glycoside (2), were isolated from a marine-derived fungus Aspergillus sp. The structures of new compounds were elucidated through interpretations of spectroscopic evidence and high-resolution electrospray ionization mass spectrometry. The hexose unit of 1 was identified as ß-D-glucose by comparison with an authentic sample via HPLC after acid hydrolysis and derivatization. All compounds were evaluated for their ability to inhibit LPS-induced NO production in RAW264.7 macrophages, but none of them displayed significant activity.

Substrate-Controlled Cu(OAc)2-Catalyzed Stereoselective Semi-Reduction of Alkynes with MeOH as the Hydrogen Source.

A substrate-controlled stereoselective semi-reduction of alkynes with MeOH as the hydrogen source has been developed, and readily available Cu(OAc)2 (copper acetate) is utilized as an optimal catalyst. The detailed investigation of the mechanism revealed distinct catalytic processes for the (Z)- and (E)-alkenes, respectively. As a result, a diversity of alkynes (including terminal, internal alkynes etc.) were compatible under the mild reaction conditions. Furthermore, the high proportion of deuterium in Z-alkenes (up to 96%) was obtained using d 4-methanol as a solvent.

Piperazine-2,5-dione derivatives and an α-pyrone polyketide from Penicillium griseofulvum and their immunosuppression activity.

Four undescribed piperazine-2,5-dione derivatives designated janthinolides C-F, and an α-pyrone-containing polyketide namely trichopyrone C, were isolated from the extract of the fungus Penicillium griseofulvum along with four known products. Among them, janthinolide C represents the first naturally occured piperazine-2,5-dione analogue featuring a cleavaged piperazinedione ring with an oxime group, while the structure of janthinolide D possesses a rare N-methoxy group in natural products. Their structures and absolute stereochemistry were elucidated based on spectroscopic data, theoretical NMR and ECD calculations, Snatzke's method, and modified Mosher's method. All compounds were evaluated for in vitro immunosuppression activity in murine splenocytes stimulated by anti-CD3/anti-CD28 mAbs, of which janthinolides B and C showed potential inhibitory activity with IC50 values at 9.3 and 1.3 µM, respectively.

Amide Iridium Complexes As Catalysts for Transfer Hydrogenation Reduction of N-sulfonylimine.

Sulfonamide moieties widely exist in natural products, biologically active substance, and pharmaceuticals. Here, an efficient water-soluble amide iridium complexes-catalyzed transfer hydrogenation reduction of N-sulfonylimine is developed, which can be carried out under environmentally friendly conditions, affording a series of sulfonamide compounds in excellent yields (96-98%). In comparison with organic solvents, water is shown to be critical for a high catalytic transfer hydrogenation reduction in which the catalyst loading can be as low as 0.001 mol %. These amide iridium complexes are easy to synthesize, one structure of which was determined by single-crystal X-ray diffraction. This protocol gives an operationally simple, practical, and environmentally friendly strategy for synthesis of sulfonamide compounds.

Cyclometalated Iridium Complex-Catalyzed N-Alkylation of Amines with Alcohols via Borrowing Hydrogen in Aqueous Media.

This paper develops a methodology for cyclometalated iridium complex-catalyzed N-alkylation of amines with alcohols via borrowing hydrogen in the aqueous phase. The cyclometalated iridium catalyst-mediated N-alkylation of amines with alcohols displays high activity (S/C up to 10,000 and yield up to 96%) and ratio of amine/imine (up to >99:1) in a broad range of substrates (up to 46 examples) using water as the green and eco-friendly solvent. Most importantly, this transformation is simple, efficient, and can be performed at a gram scale, showcasing its potential for industrially synthesizing N-alkylamine compounds.

Structurally Diverse Meroterpenoids from a Marine-Derived Aspergillus sp. Fungus.

Three new meroterpenoids, asperaustins A-C (1-3), and seven known analogues (4-10) were isolated from a marine-derived Aspergillus sp. fungus. The structures and absolute configurations of these new compounds were unequivocally determined by extensive spectroscopic analyses and single-crystal X-ray diffraction analyses. Asperaustin A (1) possesses an unusual spiro[4.5]deca-3,6-dien-2-one moiety with a unique 5/6/6/6/5 pentacyclic skeleton. The absolute configurations of austinoneol A (7) and precalidodehydroaustin (9) were determined by single-crystal X-ray diffraction analyses using Cu Kα radiation for the first time.

Phenolic C-Glycosides and Aglycones from Marine-Derived Aspergillus sp. and Their Anti-Inflammatory Activities.

A chemical investigation of the secondary metabolites of a marine-derived Aspergillus sp. led to the isolation and characterization of 13 phenolic compounds, including 10 new compounds (1-10). Seven new compounds (1-7) are unusual phenolic C-glycosides, while the other new compounds (8-10) are structurally related aglycones. The chemical structures of these new compounds were elucidated by 1D and 2D NMR and HRESIMS spectroscopic analyses. The absolute configurations of these new C-glycosides were determined by comparison of experimental electronic circular dichroism spectra with those of calculated ones. In addition, the anti-inflammatory activities of these compounds were evaluated, and compound 9 significantly inhibited nitric oxide production with an IC50 value of 6.0 ± 0.5 µM in lipopolysaccharide-induced RAW264.7 cells. Moreover, compound 9 also showed anti-inflammatory activity by inhibiting the NF-κB-activated pathway.

Three New Indole Diketopiperazine Alkaloids from Aspergillus ochraceus.

Asperochramides A - D (1 - 4), a new natural product and three new indole diketopiperazine alkaloids, along with seven known analogs (5 - 11), were isolated from the ethyl acetate extract of Aspergillus ochraceus. Their structures were elucidated by extensive spectroscopic analyses, ECD calculation, and single-crystal X-ray diffraction analysis. Compounds 3 and 4 represent a rare group of indole diketopiperazine alkaloid with a 3-hydroxyl-2-indolone moiety. The in vitro anti-inflammatory effects of compounds 1 and 3 - 11 were investigated by using LPS-stimulated murine macrophage RAW 264.7 cells. Compounds 1, 8, 10, and 11 showed potential anti-inflammatory activities.

2-[(5,7-Dibromo-quinolin-8-yl)-oxy]-N-(2-meth-oxy-phen-yl)acetamide.

In the title compound, C(18)H(14)Br(2)N(2)O(3), an intra-molecular N-H⋯N hydrogen bond forms an eight-membered ring. The dihedral angle between the planes of the quinoline system and the benzene ring is 41.69 (1)°. The crystal packing is stabilized by inter-molecular C-H⋯O hydrogen bonds and short Br⋯O inter-actions [3.0079 (19) Å].