Reaction mechanism and chemotaxonomy in the formation of the type I indole alkaloids derived from secologanin

Abstract

The history of biomolecules is written into the structure of their educts and products. The group of indole alkaloids derived from secologanin and tryptamine has more than 2000 individual compounds isolated mainly from the Rubiaceae, Loganiaceae, and Apocynaceae plant families and having strictosidine as a common precursor. To detect their history in its main lines, the compounds isolated from the same or closely related species were ordered as intermediates into reaction sequences according to the principles of basic organic reaction mechanisms. The analysis is restricted to the main lines of the monomeric alkaloids having one un-rearranged secologanin subunit (type I) closed to N-4 atom and one tryptamine subunit in intact or cleaved form. Deglucosylation of strictosidine opens the way for different types of cyclizations. Subsequent key bond-braking and bond-making reactions involve bond C-5-C-6 in the tryptamine subunit, bond C-15-C-16 in the secologanin subunit, and bond C-3-C-7 at the attachment of the two subunits, and indicate the crucial importance of a strong long-range through-bond interaction between the two nitrogen atoms. With a few principles it was possible to interpret such important biogenetic-type steps, as the formation of the akuammidan and akuammilan bridges, the transition from the vincosan into the strychnan and further to the aspidospermatan skeleton, the breaking and transformation of the side-chain of the triptamine subunit and the cleavage of the strategic bond C-15-C-16 toward the formation of the formation of type II and type III alkaloids.

Molecular evolutionary lines in the formation of indole alkaloids derived from secologanin

“…13 Namely, the relation of the secologanin subunit and the N-4 atom corresponds in 37 to the corynanthean skeleton (11), in 47 to the malindan skeleton (10) (scheme 3).…”

“…Type I skeleton 5 contains the carbon frame in its original, type II 6 and type III 7 in a rearranged form. 11 The generation starts with strictosidine corresponding to vincosan 8 i. e. to the basic skeleton of the type I α indole alkaloids in which C-3 (analogous to C-7 in secologanin) is attached to α position (C-2) of the indole ring. After deglucosylation, the hypothetic aglucone (represented as all-oxo aglucone 4 in scheme 1) undergoes several types of cyclizations and subsequent transformations.…”

Klassiker Organikum

“…The indole framework is a component of several classes of bioactive natural compounds 1. The introduction of a β‐aminoethyl group at the C3 position of the indole ring brings us to the tryptamine family, which includes melatonin and serotonin 2. The simple and effective modification of bioactive tryptamines remains an important task in modern organic chemistry because of their highly beneficial effects for medical treatment.…”

Rigorous Biogenetic Network for a Group of Indole Alkaloids Derived from Strictosidine

“…The primarily formed aglucone 5 cannot be isolated, as it undergoes many types of isomerizations (which are represented in the trioxo form 6 in Scheme 1 ) [ 23 ]. Subsequent cyclizations and further transformations provide a high number of type I α alkaloids, whose formation was discussed previously [ 13 ].…”

“…The internal consistance was further supported by the mechanism of chirality transfer at C-15 and C-3 in the type I class of indole alkaloids, and some stereoselectivity could be demonstrated even in the type II and III classes as well [ 11 , 12 ]. Extended biogenetic networks could be established by studies in the large group of type I alkaloids [ 13 ] and in the small but highly specific group of Melodinus alkaloids [ 14 ]. In addition, a long evolutionary line was constructed for the formation of ellipticine from ajmalicine (corynanthean skeleton) and an analogous line postulated for olivacine from isodihydrocadambine (malindan skeleton) [ 15 ].…”