Iboga Indole alkaloids

Iboga ibogaine, 768 Ignatius beans, 553 llligera spp., 319 Imperialine, 732 Indaconitine, 673, 684 Indole alkaloids, 484 Indolizine, 16 Insularine, 362, 370... 

In China, the bark and leaves are used for the treatment of fractures. The roots are used in Malaysia to recover from childbirth and exhaustion, and a paste of the plant is used to treat orchitis. The plant contains indole alkaloids such as conodurinine, 19 (S) hydroxyconoduramin, 19 (S)-hydroxyervahanine A, and related iboga alkaloid congeners, and like the species mentioned earlier, and in fact the genera Ervatamia, in general, would be worth investigating for serotoninergic activities (17). 

The synthesis of tacamonine, an indole alkaloid of the Iboga type, was accomplished in both racemic and homochiral forms, by incorporating a classical 6-exo-trig radical cyclization in the key step of the synthesis (Reaction 7.57) [52], The cyclization produced piperidinone in a 72% yield as a diaster-eomeric mixture. 

L-tyrosine Tyrosine-derived alkaloids Indole alkaloids Quinoline alkaloids /3-carboline alkaloids Pyrroloindole alkaloids Ergot alkaloids Iboga alkaloids Corynanthe alkaloids Aspidosperma alkaloids Protoalkaloids Terpenoid indole alkaloids True alkaloids... 

Tacamonine, an indole alkaloid of the Iboga type, isolated from Tabermemontana eglandulosa, the root of which is used to treat snake bites in Zaire, bears structural similarity to the Hunteria alkaloids, eburnamonines, which possess vasodilator and hypotensive activities. Its synthesis in racemic and homochiral form was accomplished by incorporating a classic 6-exo-trig radical cyclization in the key step of the synthesis (Scheme 6)71. The radical precursor 6 was constructed in a 7-step synthesis by starting from racemic or chiral propane-1,3-diol. The radical cyclization of 6 produced the piperidinone in 72% yield as a diastereomeric mixture, which was then transformed into tacamonine. 

Further variants on the terpenoid indole alkaloid skeleton (Figure 6.82) are found in ibogaine from Tabemanthe iboga, vincamine from Vinca minor, and ajmaline from Rauwolfia serpentina. Ibogaine is simply a C9 Iboga type alkaloid, but is of interest as an experimental drug to treat heroin addiction. In a number of European countries, vincamine is used clinically as a vasodilator to increase cerebral blood flow in cases of senility, and ajmaline for cardiac arrhythmias. Ajmaline... 

Another all-carbon Diels-Alder reaction is proposed for the biosynthesis of the indole alkaloids tabersonine 1-6 and catharanthine 1-7 of the Aspidosperma and Iboga family [28-31]. The compounds are formed via strictosidine 1-3, the first nitrogen-containing precursor of the monoterpenoid indole alkaloids, and stemmadenine 1-4, which is cleaved to give the proposed intermediate dehy-drosecodine 1-5 with an acrylate and a 1,3-butadiene moiety (Scheme 1-1). 

The mode of biosynthesis of none of these alkaloids is known but, in the case of the iboga group, some guesses have been made (39, 63, 64), all of which start from the amino acids, tryptophan and dihydroxy-phenylalanine, and involve a fission of the latter s aromatic ring. A more sophisticated approach (65), starting from precursors of the aromatic amino acids, namely shikimic and prephenic acids, is apparently not in agreement with recent work on other indole alkaloids (66). The genesis of most indole alkaloids appears to stem from tryptophan and three... 

Eburnamine-Vincamine Alkaloids.—So far most of the effort on indole alkaloid biosynthesis has been concentrated on the Corynanthe, Aspidosperma, and Iboga systems. It is welcome, therefore, to see the preliminary results of an investigation of the biosynthesis of vincamine (10).6 Comparable incorporations were observed for [ar-3H]tryptophan, [ar-3H]stemmadenine (5), and [ar-3H]taber-sonine (9). These results support the proposal7 that vincamine is a transformation... 

Since the last review on Picralima alkaloids was written (for Volume X) activity in this field has considerably abated and in consequence there is comparatively little new work to be reported. The main features of indole alkaloid biosynthesis have now been elucidated and the reader is referred to Battersby (1) for an authoritative summary of this fascinating topic. Preakuammicine (1) appears to be involved in the direct pathway to the Strychnos, Aspidosperma, and Iboga alkaloids, and although it has not been isolated from Picralima it is appropriate to include it here, and to note that its presence in very young seedlings of Vinca rosea has been established (2). Preakuammicine is almost certainly the precursor of akuammicine (2), a transformation which can also be achieved by treatment with base (2). 

Two new indole alkaloid skeleta have been obtained from Tabernanthe iboga Baillon and T. subsessilis Stapf in the form of the alkaloids ibophyllidine and iboxyphylline (109). 

Table II tabulates the plant species which contain the complex indole alkaloids. The letters in this table correspond to the various structural types as coded in Figs. 2 and 3. Types I, II, and III are the major variations of the Cfl-Ci 0 unit which, in combination with tryptamine, formally elaborate the three significantly different groups of complex indole alkaloids Corynanthe, Iboga, and Aspidosperma. Such initial classification follows the outline set by Battersby [3, 3a) and others (2, 4, 5). The...

It is now quite certain that the iboga alkaloids originate from tryptophan or its equivalent and two mevalonate residues (2). The latter are linked head-to-tail since geraniol can also function as a precursor of the hydroaromatic portion (3). These results along with incorporation of the same precursors in other indole alkaloids (4) confirm the earlier hypothesis (5) which was based solely on the classic method of recognizing similar units within apparently dissimilar natural products. 

Of the three major indole alkaloid classes (i) the iboga system appears to have the narrowest distribution (d). 

As a consequence of a study of the reactivity of the j3-position of the indole moiety a route to the iboga ester alkaloids has been developed (35). Treatment of ibogaine with <-butyl hypochlorite yielded 7j3-chloro-7 -ibogaine (mp 90°-92°), lithium aluminum hydride reduction of which regenerated ibogaine. The chloroindolenine reacted slowly in aqueous... 

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