Phenol oxidative coupling in the biogenesis of the macrocyclic spermine alkaloids aphelandrine and orantine in Aphelandra sp.

A crucial step in the biosynthesis of the spermine alkaloid aphelandrine an d its diastereoisomer orantine is an intramolecular cyclization of the inte rmediate (S)-dihydroxyverbacine. In order to elucidate this step of the bio synthetic pathway, microsomes from the roots of Aphelandra squarrosa Nees w ere incubated with unlabeled and (D-8)-labeled (S)-dihydroxyverbacine. It w as shown that the microsomal fraction catalyzes the intramolecular coupling of (S)-dihydroxyverbacine to aphelandrine. This was proven by microsomal t ransformation of (D-8)-labeled (S)-dihydroxyverbacine to (D-8)-labeled aphe landrine. The reaction absolutely requires NAPDH and O-2. The underlying re action mechanism is probably an oxidative phenol coupling catalyzed by an a phelandrine synthase. This enzyme is proposed to be a cytochrome P-450 oxid ase. The intramolecular cyclization of (S)-dihydroxyverbacine represents an important point in the biogenesis of the aphelandrine-type alkaloids.