Biosynthesis of antimalarial lignans from Holostylis reniformis

Holostylis reniformis biosynthesizes 8-8' linked lignans without 9,9'-oxygenation. To elucidate the biosynthetic pathways to these lignans, the reputed precursors [U-(14)C]phenylalanine, [9-(3)H(1)]coniferyl alcohol, and [9-(3)H(1)]isoeugenol were administered to roots of the plant, which led to the incorporation of (3)H and (14)C into ten 2,7' linked-lignans (aryltetralone lignans) and two 7,7'-epoxylignans (furan lignans). These administration experiments demonstrated that the lignans were propenylphenol-derived and that H. reniformis can exhibit regioselective control over radical-radical coupling (via isoeugenol radicals). Regiospecific control over propenylphenol-derived lignan biosynthesis was observed, together with diastereoselective control of C2-C7' bond formation for the aryltetralone lignans (7'R). These experiments provide evidence that isoeugenol is a biosynthetic intermediate to the aryltetralone and furan lignans.