An Accesss to 4,5,6-Trisubstituted Pyrimidines from 2H-Azirines and α-Isocyanoacetates or α-Isocyanoacetamides Enabled by 1,3-Dipolar [3 + 2] Cycloaddition/Ring-Expanding/Oxidative Aromatization Process.

The products containing pyrimidine scaffolds exhibit various important physiological and biological activities. To date, the strategies to generate 4,5,6-trisubstituted pyrimidines were not reported. Here, a copper-catalyzed reaction of 2H-azirines with α-isocyanoacetates or α-isocyanoacetamides has been developed, rapidly preparing 4,5,6-trisubstituted pyrimidines. The mechanistic results reveal that this strategy underwent a formal 1, 3-dipolar [3 + 2] cycloaddition/ring-expanding/oxidative aromatization procedure to construct the desired pyrimidines.

One-pot formal [3 + 2] annulation of 2-pyridinyl-substituted p-quinone methides and arynes for the synthesis of 3-aryl pyrido[1,2-a]indoles.

An efficient and metal-free method for the synthesis of 3-aryl pyrido[1,2-a]indoles from aryne intermediates and 2-pyridinyl-substituted p-QMs was successfully developed under ambient conditions. The reaction offered a novel and practical protocol to access some diverse functional molecules in good to excellent yields. The proposed mechanism indicated that the reaction proceeded via a formal [3 + 2] cycloaddition step.

DMSO-promoted direct δ-selective arylation of p-quinone methenylpiperidine bearinides to generate fuchsones under metal-free conditions by employing p-QMs themselves or substituted phenols as aryl sources.

Fuchsones have wide applications in modern society. Present methods for generating fuchsones have many disadvantages and there are significant limitations for further exploration of fuchsone applications. Herein, we describe a DMSO-promoted direct δ-selective arylation of p-QMs to synthesize symmetrical and unsymmetrical fuchsones under metal-free conditions by employing p-QMs themselves or substituted phenols as aryl sources. As unprecedented methods, these novel strategies present a great advantage and significance for further exploration of fuchsones and the development of new applications.

Natural manganese sand activates sodium hypochlorite to enhance ionic organic contaminants removal: Optimization, modeling, and mechanism.

Although sodium hypochlorite acting as an oxidant has been investigated for the role it plays in the degradation of organic contaminants, little attention has been paid to its activation and efficient utilization. In this study, natural manganese sand (NMS) was verified to be effective for activation of sodium hypochlorite (NaClO). Due to the generation of O2-, the removal efficiency of ionic organic contaminants in NMS/NaClO system was 1.9-4.1 times higher than that in NMS or NaClO alone. Hence, NMS activated NaClO system performed ~96.6 % contaminants removal efficiency at a wide pH range (pH 5-9). Kinetic modeling yielded that the NMS dosage was more important than NaClO dosage. Long-term stability was observed in the presence of various salts (bicarbonate, sulfate, phosphate, and chloride). Characterization results revealed that electron transfer among NMS, NaClO, and organic contaminants was responsible for NaClO activation. Then NaClO-based Fenton-like process was proposed by tracing the degradation intermediates of methyl orange (MO) and generations of reactive oxygen species in the MO/NMS/NaClO system. This study presents the potential of NMS to activate NaClO and enhance ionic organic contaminants removal from aquatic environments.

Synthesis and structure-activity relationship of non-phosphorus-based fructose-1,6-bisphosphatase inhibitors: 2,5-Diphenyl-1,3,4-oxadiazoles.

With the aim of discovering a novel class of non-phosphorus-based fructose-1,6-bisphosphatase (FBPase) inhibitors, a series of 2,5-diphenyl-1,3,4-oxadiazoles were synthesized based on the hit compound (1) resulting from a high-throughput screening (HTS). Structure-activity relationship (SAR) studies led to the identification of several compounds with comparable inhibitory activities to AMP, the natural allosteric inhibitor of FBPase. Notably, compound 22 and 27b, bearing a terminal carboxyl or 1H-tetrazole, demonstrated remarkable inhibition to gluconeogenesis (GNG). In addition, both inhibition and binding mode to the enzyme were investigated by enzymatic kinetics and in silico experiments for representative compounds 16 and 22.