5-Alkylresorcinols from Hakea trifurcata That Cleave DNA

A dichloromethane extract of Hakea trifurcata that mediated relaxation of ϕX174 replicative form DNA at micromolar concentrations in the presence of Cu²⁺ was resolved into six active components by bioassay-guided fractionation. Five of the active principles were characterized structurally and shown to be 5-alkylresorcinol derivatives. These included 1,3-dihydroxy-5-tridecylbenzene (1), 1,3-dihydroxy-5-(cis-8’-pentadecenyl)benzene (2), 1,3-dihydroxy-5-[14‘-(3“,5”-dihydroxyphenyl)-cis-6’-tetradecenyl]benzene (3), 1,3-dihyroxy-5-[14‘-(3“,5”-dihydroxyphenyl)tet-radecyl]benzene (4), and 1,3-dihydroxy-5-[16‘-(3“, 5”-dihydroxyphenyl)-cis-8‘-hexadecenyl]benzene (5). The structures of these five natural principles were confirmed by total synthesis; compounds 1—5 were accessible from 3,5-dimethoxybenzaldehyde in overall yields of 59%, 27%, 15%, 16%, and 13%, respectively.