THE FORMATION OF BENZOPHENANTHRIDINE ALKALOIDS

Isoquinoline alkaloids are a major group of pharmacologically important compounds. The universal precursor to the majority of this alkaloid class is (S)-reticuline. The biosynthesis of this important intermediate starting from the primary metabolite, L-tyrosine, has been completely solved at the enzyme level. One of the most diverse structures in the class of isoquinoline alkaloids are the benzo[c]phenanthridines. The most highly oxidized member is macarpine, an alkaloid produced in considerable quantity in cell suspension cultures of Eschscholtzia californica. This plant source was used to isolate all of the enzymes involved in this pathway. Twelve steps are necessary for the transformation of (S)-reticuline to macarpine, eleven of these are enzyme catalyzed, one is spontaneous.