Efficient Synthesis of Alkoxypyrazole- or Pyrazolone-Fused 1,4-Naphthoquinones via Ullmann Cyclization and Evaluation of Their Cytotoxicity

초록

A series of novel 3-alkoxypyrazole- and pyrazolone-fused 1,4-naphthoquinone derivatives were successfully synthesized through an intramolecular Ullmann-type cyclization, using 1,4-dihydroxy-2-naphthoic acid as the starting material. Subsequent regioselective N- or O-alkylation followed by CAN-mediated oxidation afforded the desired quinones in moderate to good yields. The molecular structures of the selected N-substituted derivatives were unambiguously confirmed by single-crystal X-ray diffraction. Preliminary cytotoxicity against RAW264.7 cells revealed that biological activity varied depending on the nature of substitution, with certain compounds exhibiting potent effects (LD50 < 5 mu M). These findings highlight the potential of fused heterocycles as promising lead structures for anticancer drug development.

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