O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization.

A one-pot three-component Biginelli synthesis of dihydropyrimidinones/thiones/selenones via acetic acid or solvent-free Yb(OTf)-catalyzed tandem reaction of β-ketosulfone (dihydro-2-thiopyran-3(4)-one-1,1-dioxide), an appropriate urea, and arylaldehyde has been developed. The reaction proceeds with high chemo- and regioselectivity to give diverse DHPMs in reasonable yields up to 95%. Moreover, an SO-containing analogue of anticancer drug-candidate enastron (SO vs C=O) was obtained by using the here reported method in gram scale.

Calcium Modulating Effect of Polycyclic Cages: A Suitable Therapeutic Approach Against Excitotoxic-induced Neurodegeneration.

Neurodegenerative disorders pose a significant challenge to global healthcare systems due to their progressive nature and the resulting loss of neuronal cells and functions. Excitotoxicity, characterized by calcium overload, plays a critical role in the pathophysiology of these disorders. In this review article, we explore the involvement of calcium dysregulation in neurodegeneration and neurodegenerative disorders.

Recent advances in visible light-induced C( )-N bond formation.

Synthetic chemists have long focused on selective C( )-N bond-forming approaches in response to the high value of this motif in natural products, pharmaceutical agents and functional materials. In recent years, visible light-induced protocols have become an important synthetic platform to promote this transformation under mild reaction conditions. These photo-driven methods rely on converting visible light into chemical energy to generate reactive but controllable radical species.

Visible Light-Induced Pd-Catalyzed Alkyl-Heck Reaction of Oximes.

A visible light-induced palladium-catalyzed oxidative C-H alkylation of oximes has been developed. This mild protocol allows for an efficient atom economical C-C bond construction of alkyl-substituted oximes. A broad range of primary, secondary, and tertiary alkyl bromides and iodides, as well as a range of different formaldoximes, can efficiently undergo this transformation.

Targeting a Cryptic Pocket in a Protein-Protein Contact by Disulfide-Induced Rupture of a Homodimeric Interface.

Interference with protein-protein interfaces represents an attractive as well as challenging option for therapeutic intervention and drug design. The enzyme tRNA-guanine transglycosylase, a target to fight Shigellosis, is only functional as a homodimer. Although we previously produced monomeric variants by site-directed mutagenesis, we only crystallized the functional dimer, simply because upon crystallization the local protein concentration increases and favors formation of the dimer interface, which represents an optimal and highly stable packing of the protein in the solid state.

Open and rearranged norbornane derived polycyclic cage molecules as potential neuroprotective agents through attenuation of MPP- and calcium overload-induced excitotoxicity in neuroblastoma SH-SY5Y cells.

The neuroprotective effects of closed polycyclic cage molecules such as NGP1-01, memantine and amantadine have been extensively explored. These effects are mostly linked to the antagonism of the N-methyl-d-aspartate (NMDA) receptor- and the blockage of voltage gated calcium channels (VGCC). The synthesis of structurally related open and rearranged cage derivatives has been studied in depth.

The formation of the salt and neutral molecule cocrystal from equimolar solution of heliamine and bicyclo[2.2.1]hept-5-ene-endo-2,3-dicarboxylic acid.

The possible interaction of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (heliamine) with bicyclo[2.2.1]hept-5-ene-endo-2,3-dicarboxylic acid anhydride has been studied.

Unique metabolites protect earthworms against plant polyphenols.

All higher plants produce polyphenols, for defence against above-ground herbivory. These polyphenols also influence the soil micro- and macro-fauna that break down plant leaf litter. Polyphenols therefore indirectly affect the fluxes of soil nutrients and, ultimately, carbon turnover and ecosystem functioning in soils.