Biosynthesis of antimalarial lignans from Holostylis reniformis

Radiolabelled precursor administrated experiments showed that lignans from Holostylis reniformis are derived from isoeugenol and that H. reniformis exhibits regioselective control of radical–radical coupling (isoeugenol radical). Regiospecific control over propenylphenol-derived lignan biosynthesis was observed, together with diastereoselective control of C2–C7′ bond for aryltetralone lignans (7′ R). Holostylis reniformis biosynthesizes 8-8′ linked lignans without 9,9′-oxygenation. To elucidate the biosynthetic pathways to these lignans, the reputed precursors [U- 14C]phenylalanine, [9- 3H 1]coniferyl alcohol, and [9- 3H 1]isoeugenol were administered to roots of the plant, which led to the incorporation of 3H and 14C 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.