FORMATION OF (-)-ARCTIGENIN IN FORSYTHIA-INTERMEDIA

Forsythia intermedia cell-free extracts were examined for their ability to catalyse the enantioselective and regiospecific O-methylation of matairesinol. In contrast to the enzymatic steps defined from (+)-pinoresinol to (-)-matairesinol, the conversion of matairesinol into arctigenin was not highly enantioselective; both (+)- and (-)- antipodes of matairesinol served as substrates for methylation, with the naturally occurring (-)-enantiomer slightly preferred. But the cell-free extracts also catalysed the synthesis of (+)- and (-)-isoarctigenins, with (-)-matairesinol again the preferred substrate. Thus the O-methylation of matairesinol, catalysed by F. intermedia cell-free extracts, is neither highly enantioselective nor regiospecific. No evidence that subsequent methylation of either arctigenin or isoarctigenin occurred to afford dimethyl matairesinol was obtained, i.e. the O-methyltransferase(s) only catalysed monomethylation. Taken together, it is proposed that post-coupling methylation does not proceed via regiospecific methylation of matairesinol to give arctigenin directly. Instead, regiospecific glucosylation first occurs to afford matairesinoside; subsequent methylation affords arctiin, which is then converted into arctigenin via action of a beta-glucosidase.