In order to find potential inhibitors of tyrosinase, two series of pyrrole derivatives A (1–17) and B (1–8) were synthesized and screened for their inhibitory activities on tyrosinase. Most of the 2-cyanopyrrole derivatives exhibited effective inhibitory activities. In particular, A12 exhibited the strongest inhibitory activities, with the IC50 values of 0.97 μM, which is ∼30 times stronger than the reference inhibitor kojic acid (IC50: 28.72 μM). The inhibitory mechanism analysis results revealed that A12 was a reversible and mixed-type inhibitor. Molecular docking experiments clarified the interaction between A12 with tyrosinase. Furthermore, A12 (100 μM) presented effective inhibitory effect on tyrosinase in B16 melanoma cells with inhibition of 33.48%, which was equivalent to that of Kojic acid (39.81%). Accordingly, compound A12 may serve as the lead structure for the further design of potent tyrosinase inhibitors. Molecular docking studies confirmed the interaction between the compound and tyrosinase.

The first total synthesis of (±)-furanether A, which exhibits good antifeedant activity, has been concisely achieved in 13 linear steps. Notably, the key rigid tetracyclic skeleton containing a 1-methyl-8-oxabicyclo[3.2.1]­octane moiety with two vicinal quaternary carbon centers was rapidly constructed in one step through a unique tandem C–H oxidation/oxa-[3,3] Cope rearrangement/aldol cyclization sequence.

An efficient alkylcyanation of in situ generated arynes by N,N-disubstituted aminomalononitriles is described, enabling the direct synthesis of 2-substituted benzonitriles.

The development of new synthetic methodology and reagent is always a hot topic in organic synthesis community. Among the strategies used, chemical property investigation of synthetic intermediates with multifunctional groups represents a direct and efficient way. In this paper, as a systematic continuation of α-aminomalononitrile based synthetic application studies, α-aminomalononitrile has been developed for the first time as a surrogate for carbamoyl anions and applied to the synthesis of tertiary amides via a copper-catalyzed decyanation reaction. This strategy features simple reaction conditions, scalability, and wide substrate scope. This work not only further enriches the reaction model of aminonitrile compounds, but also provides an alternative synthetic strategy for the synthesis of substituted amides from simple formamides. In this process, the substrates could be readily synthesized through the nucleophilic addition or substitution reaction of α-aminomalononitriles, and they would be converted to corresponding tertiary amide in the presence of CuF 2 in DMSO. As an example, the formal hydrocarbamoylation reaction of unsaturated bonds could be achieved. A general procedure for the strategy is as follows: α-aminomalononitrile derived from formamide is used to undergo nucleophilic addition or substitution reaction with electrophilic reagents. Next, the two cyano groups of the synthesized substrates could be removed under the catalysis of CuF 2 to form a C＝O double bond in situ, thereby achieving the synthesis of corresponding tertiary amide. During the reaction, the α-aminomalononitrile substrate (0.4 mmol), CuF 2 (5 mol%), DMSO (3 mL) were placed in a sealed reaction tube at 100 ℃ at an argon atmosphere for about 32 hours. Then, the reaction system was washed out with ethyl acetate, and the organic phase was washed with water to remove DMSO. Next, the aqueous phase was extracted with ethyl acetate. Finally all organic phases were combined, washed once with saturated brine. After drying the organic phase over anhydrous sodium sulfate, it was concentrated by a vacuum pump. Finally, the residue was purified by flash column chromatography to give amide product.

A synthesis of 1‐cyano‐bisindolylmethane analogues via an Al(OTf)3‐catalyzed tandem coupling reaction between N,N‐disubstituted aminomalonitriles and substituted arenes has been developed. This method not only provides an alternative synthetic strategy for the synthesis of corresponding functional molecules, but also enriches the volume of bisarylmethanes library to facilitate related functional studies.magnified image