Synthesis and bioactivity of erythro-nordihydroguaiaretic acid, threo-(-)-saururenin and their analogues

Abstract

Full details of the total syntheses of erythro-nordihydroguaiaretic acid, threo-(-)-saururenin and their analogues are presented. The syntheses were based on a unified synthetic strategy involving the Stobbe Reaction, alkylation to construct the skeleton of lignans and resolution of the threo- and erythro-isomers. The syntheses were achieved in eight to nine steps from simple aromatic precursors, and by this route 13 lignans were obtained. Among the synthesized lignans, seven lignans were natural products; moreover three of the seven natural products were synthesized for the first time. The effect of 13 lignans was examined on HIV Tat transactivation in human epithelial cells, HSV-1 gene and human leukemic, liver, prostate, stomach and breast cancer cell. Bioactivity results indicated that one product showed activity against the HIV gene and five compounds exhibited anti-HSV activity.