Biosynthesis of aristolochic acid

Abstract

The incorporation of tyrosine, (3,4-dihydroxyphenyl)alanine, nororientaline, orientaline, prestephanine, and stephanine into aristolochic acid in Aristolochic bracteata has been studied; specific utilisation of nororientaline has been demonstrated. The evidence strongly supports the hypothesis that the oxidative coupling of orientaline gives prestephanine, which is converted into stephanine; oxidative cleavage of stephanine then furnishes aristolochic acid. An experiment with doubly labelled nororientaline showed its incorporation intact into the product, and confirmed the view that the methylenedioxy-group in aristolochic acid originates from an o-methoxyphenol precursor. Parallel feedings of (–)- and (+)-orientaline confirmed that stereospecificity is maintained in the biosynthesis of aristolochic acid from the 1-benzyltetrahydroisoquinoline precursors.