Phosphoric Acid Catalyzed N-Addition/ C-Addition Reaction of 3-Vinyl Indoles with Pyrazole/Pyrazolone to Construct Pyrazole-Substituted 3-(1-Heteroarylethyl)-indole Scaffolds.

Developing a highly efficient atom-economic method for the preparation of 3-(1-heteroarylethyl)-indole scaffolds is of significant value in pharmaceutical and agricultural chemistry. Herein, a phosphoric acid-catalyzed N-addition reaction of 3-vinyl indoles with pyrazoles and C-addition reaction of 3-vinyl indoles with pyrazolones were developed. A series of pyrazole-substituted 3-(1-heteroarylethyl)-indole scaffolds were synthesized in excellent yields (up to 99% yield) under mild reaction conditions. A reasonable reaction mechanism was proposed to explain the experimental results.

Thiopental sodium attenuates hypoxia/reoxygenation-induced injury in osteoblasts by modulating AKT signaling.

Thiopental sodium (TPTS) is a barbiturate general anesthetic, while its effects on hypoxia/reoxygenation (H/R)-induced injury are still unclear. This study aimed to investigate whether TPTS exerts protective effects against the H/R-induced osteoblast cell injury and explore the underlying mechanisms. Osteoblast cell injury model was induced by the H/R condition, which was treated with or without TPTS. Cell viability and lactate dehydrogenase (LDH) release were determined by the corresponding commercial kits. The levels of oxidative stress were determined in the experimental groups. Cell apoptosis and Caspase-3 activities were determined by propidium iodide staining and substrate-based assay, respectively. Western blotting and qRT-PCR were performed to measure the mRNA and protein levels, respectively. Treatment with TPTS was able to increase cell viability and reduce LDH release in H/R-induced osteoblasts. Additionally, TPTS regulated oxidative stress in H/R-induced osteoblasts by suppressing malondialdehyde (MDA) and reactive oxygen species (ROS) as well as boosting superoxide dismutase (SOD). TPTS was able to suppress cell apoptosis by suppressing Caspase-3 activity and cleavage. TPTS exerted protective effects against cell injury and apoptosis induced by the H/R conditions, which were associated with its regulation of Akt signaling. Moreover, TPTS induced osteoblast differentiation under the H/R condition. In summary, TPTS attenuates H/R-induced injury in osteoblasts by regulating AKT signaling.

Rh(II)/Pd(0) Dual Catalysis: Interception of Ammonium Ylide with Allyl Palladium to Construct 2,2-Disubstituted Tetrahydroquinoline Derivatives.

New synthetic methods to construct 2,2-disubstituted tetrahydroquinoline derivatives are of significant value in pharmaceutical chemistry. Herein, a Rh(II)/Pd(0) dual-catalyzed diazo α-aminoallylation reaction has been developed between allylpalladium(II) and ammonium ylides derived from the Rh2(OAc)4-mediated intramolecular N-H bond insertion reaction of diazo compounds, affording various 2,2-disubstituted tetrahydroquinoline derivatives in good yields up to 93% with high chemoselectivities under mild reaction conditions. A substrate scope investigation reveals broad ester substituent tolerance, and control experiments provide the basis for a proposed reaction mechanism.

Rearrangement of N-tert-Butanesulfinyl Enamines for Synthesis of Enantioenriched α-Hydroxy Ketone Derivatives.

Treating chiral N-tert-butanesulfinyl ketimines with potassium hexamethyldisilazide (or potassium tert-butoxide) and methyl triflate gives N-methylated N-tert-butanesulfinyl enamine intermediates that undergo stereoselective [2,3]-rearrangement to afford α-sulfenyloxy ketones with excellent enantiopurities. This cascade of enamination-N-methylation-rearrangement was even used to generate acyclic tertiary α-hydroxy ketones bearing two α-substituents showing negligible differences in bulkiness, such as methyl and ethyl groups.

Aldol Reaction of N-tert-Butanesulfinyl Imidates under Basic Conditions for Diastereoselective Synthesis of anti-Aldols.

Diastereoselective aldol reaction of N-tert-butanesulfinyl imidates under typical hard enolization conditions is reported. Potassium bis(trimethylsilyl)amide (KHMDS) effectively promotes the aldol reaction of α-aryl- and α-alkyl-substituted imidates, providing anti-aldol adducts in high yields with good to excellent diastereoselectivities. In the case of α-aryl imidates, high conversion depends on adding trimethylsilyl chloride (TMSCl) to the reaction mixture. In the presence of a suitable Lewis acid, cyclohexanone is a good electrophile in the aldol reaction of imidates.