Regioselective C3Alkylation of Indoles for the Synthesis of Bis(indolyl)methanes and 3-Styryl Indoles.

Herein, we describe an efficient transition-metal-free regioselective C3alkylation of indoles for the synthesis of bis(indolyl)methanes and 3-styryl indoles. Nitrobenzene is employed as the oxidant to oxidize the alcohols in the presence of a strong base and the reaction avoids the use of transition metals such as Ru and Mn. The protocol provides a favorable route to access biologically active compounds such as arundine, vibrindole A, and turbomycin B.

Oxidant/Solvent-Controlled I2-Catalyzed Domino Annulation for Selective Synthesis of 2-Aroylbenzothiazoles and 2-Arylbenzothiazoles under Metal-Free Conditions.

A simple and practical domino protocol for the selective synthesis of 2-aroylbenzothiazoles and 2-aryl benzothiazoles catalyzed by I2 is developed under metal-free conditions. The reaction outcomes are exclusively controlled by the reaction oxidant/medium. With DMSO employed as both the solvent and the oxidant, an oxidation of aromatic methyl ketones takes precedence over the condensation with 2-aminobenzenethiols. On the other hand, when the reaction was carried out in PhNO2 or in 1,4-dioxane containing PhNO2, the condensation of aromatic methyl ketones with 2-aminobenzenethiols has priority to form imines which is followed by an oxidation of the methyl group from ketones to afford 2-arylbenzothiazoles as a sole product. The PhNO2/I2 co-catalytic system is proposed first time.

Sustainable Four-Component Annulation for the Synthesis of 2,3,4,6-Tetraarylpyridines.

A one-pot, four-component annulation of 2,3,4,6-tetraarylpyridines from aromatic aldehydes, methyl ketones, diaryl ethanones, and ammonium acetate is described. The reaction features high functional group compatibility in air under solvent-free conditions without any additive and only water as the nontoxic byproduct, providing a strategy for the facile, economical, and eco-friendly construction of multiaryl-substituted pyridines from simple and readily available reactants.

Synthesis of 1,2-dihydro-1,3,5-triazine derivatives via Cu(II)-catalyzed C(sp3)-H activation of N,N-dimethylethanolamine with amidines.

1,2-Dihydro-1,3,5-triazines and symmetrical 1,3,5-triazines were obtained in up to 81% yields from amidines and N,N-dimethylethanolamine catalyzed by CuCl2. The reaction involves three C-N bond formations during the oxidative annulation process and the mechanism was proposed. This efficient synthesis of 1,2-dihydro-1,3,5-triazines was developed for the first time.

Combined effects of aging and low temperature, long time heating on pork toughness.

The combined effects of aging and low temperature, long time heating (LTLT) on meat toughness were investigated. Pork loins were heated at 53 or 58 °C for up to 20 h, and shear force values, cooking loss, moisture content, collagen solubility, electrophoresis of myofibrillar proteins were determined. Structural changes in perimysium were also observed by light microscopy and scanning electron microscopy (SEM). Results showed that aging and LTLT cooking independently affected meat toughness, and higher temperature or longer time were required to decrease toughness of one-day aged meat to the same level as in 10-day aged meat. Collagen solubilization is suggested as the main reason for the tenderization effect of LTLT. Myofibrillar proteolysis might not occur during LTLT cooking, and will not be contributing to meat tenderness.

Novel 1,3,4-Selenadiazole-Containing Kidney-Type Glutaminase Inhibitors Showed Improved Cellular Uptake and Antitumor Activity.

Kidney-type glutaminase [KGA/isoenzyme glutaminase C (GAC)] is becoming an important tumor metabolism target in cancer chemotherapy. Its allosteric inhibitor, CB839, showed early promise in cancer therapeutics but limited efficacy in in vivo cancer models. To improve the in vivo activity, we explored a bioisostere replacement of the sulfur atom in bis-2-(5-phenylacetamido-1,2,4-thiadiazol)ethyl sulfide and CB839 analogues with selenium using a novel synthesis of the selenadiazole moiety from carboxylic acids or nitriles. The resulting selenadiazole compounds showed enhanced KGA inhibition, more potent induction of reactive oxygen species, improved inhibition of cancer cells, and higher cellular and tumor accumulation than the corresponding sulfur-containing molecules. However, both CB839 and its selenium analogues show incomplete inhibition of the tested cancer cells, and a partial reduction in tumor size was observed in both the glutamine-dependent HCT116 and aggressive H22 liver cancer xenograft models. Despite this, tumor tissue damage and prolonged survival were observed in animals treated with the selenium analogue of CB839.