Synthesis and Cytotoxic Activity of Benzopyranoxanthone Analogues of Benzo[b]acronycine and Psorospermine

Abstract

Condensation of 3-hydroxy-2-naphthalenecarboxylic acid with phloroglucinol afforded 1, 3-dihydroxy-12H-benzo[b]xanthen-12-one. Construction of an additional dimethylpyran ring onto this skeleton, by alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement, gave access to a series of benzo[b]pyrano[2, 3-i]xanthen-6-ones and benzo[b]pyrano[3, 2-h]xanthen-7-ones related to psorospermine and benzo[b]acronycine. In contrast with what is observed in the pyridoacridone and benzopyridoacridone series, the linear benzo[b]-pyrano[2, 3-i]xanthen-6-one derivatives were more potent than their angular benzo[b]pyrano[3, 2-h]xanthen-7-one isomers. cis-3, 4-Diacetoxy-5-methoxy-2, 2-dimethyl-3, 4-dihydro-2H, 6H-benzo[b]pyrano[2, 3-i]xanthen-6-one, the most active among the new compounds, was more potent than acronycine in inhibiting the proliferation of L1210 murine leukemia cells.