A revision of the generally accepted pathway for the biosynthesis of the benzyltetrahydroisoquinoline alkaloid reticuline

The label from (S)‐[1‐13C]norcoclaurine and (S)‐[1‐13C]co‐claurine was highly and nonrandomly incorporated into (S)‐reticuline in benzyltetrahydroisoquinoline‐producing plant cell cultures of Berberis stolonifera, Eschscholtzia californica and Peumus boldus. From the intermediates observed in vivo we conclude that (S)‐norcoclaurine is stereoselectively metabolized to (S)‐reticuline via (S)‐coclaurine, (S)‐N‐methylcoclaurine and (S)‐3′‐hydroxy‐N‐methylcoclaurine. These results confirm a revised pathway to the benzylisoquinoline alkaloids.