Synthesis and anticancer properties of new (dihydro)pyranonaphthoquinones and their epoxy analogs

1,4-Dihydroxy-2-naphthoic acid was used as a substrate for a straightforward five-step synthesis of 3-substituted 1H-benzo[g]isochromene-5,10-diones, with a Michael addition of N-acylmethylpyridinium ylides across 2-hydroxymethyl-1,4-naphthoquinone and a subsequent acid-mediated dehydratation of intermediate hemiacetals as the key steps. The obtained benzo[g]isochromene-5,10-diones were subsequently deployed for further synthetic elaboration to produce new 3,4-dihydrobenzo[g]isochromene-5,10-diones and (3,4-dihydro-)4a,10a-epoxybenzo[g]isochromene-5,10-diones. All compounds were screened for their cytotoxic and antimicrobial effects, revealing an interesting cytotoxic activity of 1H-benzo[g]isochromene-5,10-diones against different cancer cell lines.