L. Nezbedova et al., Phenol oxidative coupling in the biogenesis of the macrocyclic spermine alkaloids aphelandrine and orantine in Aphelandra sp., PLANTA, 213(3), 2001, pp. 411-417
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.