Biosynthesis of linear furanocoumarins

Abstract

Labelling experiments with 14C and 3H have shown that linear furanocoumarins of Ammi majus, Angelica archangelica, Heracleum lanatum (Umbelliferae), and Ruta graveolens (Rutaceae) are formed from umbelliferone via the dihydrofuranocoumarin, marmesin. The unsubstituted furanocoumarin psoralen is formed first, and hydroxylation and O-methylation then lead to methoxy-substituted derivatives, with other alkylated psoralens assumed to be formed analogously. No evidence was obtained for oxygenation of the coumarin nucleus before attachment of a side chain, since oxygenated umbelliferones were poorly utilized for furanocoumarin biosynthesis. A detailed biosynthetic route to linear furanocoumarins, consistent with known stereochemistry, is proposed.A separation of furanocoumarins by column partition chromatography on formamide-impregnated silica, and syntheses of [3-14C]umbelliferone, [2-14C]- and [3-14C]skimmin, [3-14C]daphnetin, [2-14C]-7-hydroxy-8-methoxycoumarin, and [2-14C]5-methoxy-7-hydroxycoumarin are described.