Isoflavonoid biosynthesis: concerning the aryl migration

Abstract

Feeding experiments with 13C- or 2H-labelled precursors in CuCl2-treated red clover (Trifolium pratense) seedlings have demonstrated that the isoflavone formononetin (6) and the pterocarpan phytoalexins medicarpin (10) and maackiain (11) are biosynthesized from 2′,4,4′-trihydroxychalcone by a rearrangement process involving an intramolecular migration of the cinnamate-derived aromatic ring. In all three compounds, this is accompanied by retention of the chalcone's β-hydrogen but loss of the α-hydrogen. During the formation of maackiain from formononetin, an NIH shift of 2H as a result of aromatic hydroxylation ortho to the methoxy group was observed. Experiments with 7-hydroxy-4′-methoxy[2-2H2]isoflavanone indicate that this compound may be converted into medicarpin without loss of 2H, thus confirming the existence of a metabolic grid of isoflavones and isoflavanones. The results are best explained in terms of an oxidative process in which a chalcone is converted into an isoflavone as the first-formed isoflavonoid derivative.