A preparative synthesis of lapachol and related naphthoquinones

Article abstract of DOI:10.1016/S0040-4039(98)01880-2

The lithium salt of 2-hydroxy-1,4-naphthoquinone was prepared in situ by addition of lithium hydride to the frozen solution of the quinone in dimethyl sulfoxide. As the solution thawed, the lithium quinone was slowly formed and was then alkylated with 3,3-dimethylallyl bromide. Lapachol was thus obtained in 40% yield. When treated with m-chloroperoxybenzoic acid it was converted into its epoxide, that was cyclized with boron trifluoride etherate to 3- hydroxy-β-lapachone in 67% overall yield. Esters of the latter were prepared by condensation with carboxylic acid derivatives using 1,1 '- carbonyldiimidazole and DBU as condensing agents.