We have designed and synthesized a series of bioinspired pyrano[2,3-f]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction. Antiviral assay of the synthesized compounds showed that compound 4 has moderate activity against HIV-1 on enzymes and poor activity on the cell model. A molecular docking study demonstrates a good correlation between in silico and in vitro HIV-1 reverse transcriptase (RT) activity of the compounds when docked to the nonnucleoside RT inhibitor binding site, and alternative binding modes of the considered analogs of Calanolide A were established.
A different type of MnO2-induced oxidative cyclization of dihydrotriazines has been developed. These dihydrotriazines are considered as a "formal" Schiff's base. This method provided easy access to naphthofuro-fused triazine via the C-C/C-O oxidative coupling reaction. The reaction sequence comprised the nucleophilic addition of 2-naphthol or phenol to 1,2,4-triazine, followed by oxidative cyclization. The scope and limitations of this novel coupling reaction have been investigated. Further application of the synthesized compound has been demonstrated by synthesizing carbazole-substituted benzofuro-fused triazines. The scalability of the reaction was demonstrated at a 40 mmol load. The mechanistic study strongly suggests that this reaction proceeds through the formation of an O-coordinated manganese complex.
Schiff Bases , Triazines , Cyclization , Manganese , Manganese Compounds , Oxides , Carbazoles , Phenols , Oxidative Stress
