Catalyst-controlled directing group translocation in the site selective C-H functionalization of 3-carboxamide indoles and metallocarbenes.

Complementary methods toward the selective functionalization of indole and oxindole frameworks employing an alternative strategy in heteroaryl C-H functionalizations are presented herein. This work focuses on a catalyst-controlled, site selective C-H activation/functionalization of 3-acyl indoles, wherein an amide serves as a robust and versatile directing group capable of undergoing concomitant 1,2-acyl translocation/C-H functionalization in the presence of a Rh/Ag co-catalysts to provide the cross-coupled adducts in high yields. In contrast, the use of Ir/Ag catalysts subverted the 1,2-acyl migration to afford the corresponding C2-functionalized products in good to excellent yields.

Streptolysin S targets the sodium-bicarbonate cotransporter NBCn1 to induce inflammation and cytotoxicity in human keratinocytes during Group A Streptococcal infection.

Group A (GAS, ) is a Gram-positive human pathogen that employs several secreted and surface-bound virulence factors to manipulate its environment, allowing it to cause a variety of disease outcomes. One such virulence factor is Streptolysin S (SLS), a ribosomally-produced peptide toxin that undergoes extensive post-translational modifications. The activity of SLS has been studied for over 100 years owing to its rapid and potent ability to lyse red blood cells, and the toxin has been shown to play a major role in GAS virulence .

Generation of Functionalized Azepinone Derivatives via a (4 + 3)-Cycloaddition of Vinyl Ketenes and α-Imino Carbenes Derived from -Sulfonyl-triazoles.

An intermolecular Rh-catalyzed, formal (4 + 3)-cycloaddition between vinyl ketenes and -sulfonyl-1,2,3-triazoles for the construction of azepinone products is described. Employing vinyl ketenes as a 1,4-dipolar surrogate, instead of the more commonly used dienyl moieties, allows for the intermolecular and selective formation of azepinone products over a potential (3 + 2)-cycloadduct under mild reaction conditions allows for the generation of azepinone products in up to 98% yield.

Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System.

Deregulation of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) plays a significant role in developmental brain defects, early-onset neurodegeneration, neuronal cell loss, dementia, and several types of cancer. Herein, we report the discovery of three new classes of N-heterocyclic DYRK1A inhibitors based on the potent, yet toxic kinase inhibitors, harmine and harmol. An initial in vitro evaluation of the small molecule library assembled revealed that the core heterocyclic motifs benzofuranones, oxindoles, and pyrrolones, showed statistically significant DYRK1A inhibition.

Ionic liquid enables highly efficient low temperature desalination by directional solvent extraction.

Seawater desalination plays a critical role in addressing the global water shortage challenge. Directional Solvent Extraction (DSE) is an emerging non-membrane desalination technology that features the ability to utilize very low temperature waste heat (as low as 40 °C). This is enabled by the subtly balanced solubility properties of directional solvents, which do not dissolve in water but can dissolve water and reject salt ions.

Diverting β-Hydride Elimination of a π-Allyl Pd Carbene Complex for the Assembly of Disubstituted Indolines via a Highly Diastereoselective (4 + 1)-Cycloaddition.

A Pd-catalyzed formal (4 + 1)-cycloaddition approach to 2,3-disubstituted dihydroindoles is described. The diastereoselective formation of dihydroindoles that is highlighted by a carbene migratory insertion/reductive elimination sequence proceeding via a π-allyl Pd-species compliments existing methods of indoline assembly.