RESUMO
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 â¼30 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.
RESUMO
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.
RESUMO
An efficient alkylcyanation of in situ generated arynes by N,N-disubstituted aminomalononitriles is described, enabling the direct synthesis of 2-substituted benzonitriles.