Dihydroxyverbacine is the terminal precursor in the biosynthesis of aphelandrine and orantine

Polyamine alkaloids

“…The biogenesis of the macrocyclic spermine alkaloids aphelandrine and its diastereomer orantine, isolated from different Aphelandra species (Acanthaceae), was carefully studied, and the results obtained so far are summarized in Scheme 8. 70 Scheme 8 Biogenetic relationships of aphelandrine, orantine and open-chain precursors proposed by Nezbedová et al 70 The investigations suggest that N 1 -cinnamoyl spermine might cyclize enantioselectively to (S)-protoverbine in an aza-Michael reaction. The enzyme responsible to connect the N( 14)-atom of spermine with the b-C-atom of the acid moiety seems to be the same in all plants that produce aphelandrine and chaenorhine type alkaloids, because all of these compounds are (S)-configured at the respective stereogenic center.…”

Biomimetic Formation of Macrocyclic Spermine Alkaloids

“…In an additional step, prelandrine has to be transformed into (S)-dihydroxyverbacine ((S)-10). Another possibility is the formation of buchnerine (14) from 11c, after aza-Michael addition, its further acylation to [(E)-4-methoxycinnamoyl]buchnerine (15), followed by transformation to 10. It is also possible that 10 is formed by an aza-Michael addition of the N,N'-dicoumaroylspermine (16) [9].…”

“…Prelandrine (13) was detected in the roots of A. squarrosa [14]. The formation of aphelandrine (1) was realized after microsome-assisted oxidation of (S)-dihydroxyverbacine ((S)-10) and its D 8 -labeled analogue [15] [16].…”

“…There are several types of heme proteins that contain the iron protoporphyrin IX group ± hemoglobins and myoglobins that are responsible for the storage and the transport of O 2 , and cytochromes that are involved in the transfer of electrons. The ability of cytochrome P-450 to promote the oxidative phenol coupling of 10 to aphelandrine (1) has recently been demonstrated [15]. Although, to the best of our knowledge, neither hemin (see Scheme 5) nor any analogous heme protein has been used for oxidative phenol coupling, it seemed appropriate to apply it as reagent in H 2 O 2 oxidation experiments.…”