Iboga alkaloids oxidation

Iboga alkaloids devoid of the 19-hydroxy group are significantly more stable toward oxidation than are the corresponding hydroxy bases. Abstraction of the hydroxy proton of 7-hydroxyindolenines by bases leads to concomitant carbon migration and formation of pseudoindoxyls. In some cases the rearrangement is better accomplished by warm HC1. The interrelationship among indoles, 7-hydroxyindolenines, and pseudoindoxyls has been exhaustively treated by Cordell (see Ref. 6). 

From Stemmadenia donnell-smithii, besides iboga alkaloids and voac-amine, the indole (+ )-quebrachamine (L), mp 147°—149°, [a]D +111° (CHCI3), and the indole stemmadenine (LIV, a— x or a— y bond), mp 199°-200° (dec.), [ ]D + 324° (pyridine), were isolated (11). The latter alkaloid also occurs in Diplorrhynchus condylocarpon (43) along with condylocarpine, shown (43a), to be LV (rather than LVI), and into which it was converted by potassium permanganate oxidation (44). Stem-... 

Details have been published of the total syntheses of velbanamine, isovel-banamine, cleavamine, 18/3-carbomethoxycleavamine, and catharanthine. Rosen-mund s route to the iboga alkaloids has now been appropriately modified to yield ibogamine and ibogaine, in addition to epi-ibogamine, and details of this work are also available. Hydroboration-oxidation of (227), presumably obtained by a thio-Claisen rearrangement [cf. (200)- (201)] affords the alcohol (228) which is a key intermediate in a Kutney-type synthesis of cleavamine however, details of the synthesis are not yet available. ... 

In support of an ingenious scheme for the biosynthesis of vinca and iboga alkaloids proposed by Wenkert is an interesting synthesis accomplished by Kutney, Brown, and Piers by transannular cyclization of carbomethoxydihydrocleavamine (I), accomplished by oxidation with mercuric acetate in acetic acid at room temperature. Chromatography afforded as the main product the vinca alkaloid vincadifformine. 

Oxidation and rearrangement products of parent bases D, Some other bases isolated with the iboga alkaloids ... 

The iboga alkaloids behave differently from the vincadifformine group on photochemical oxidation iboxyphylline is rapidly oxidised at C-16 to give a hydroxy-indolenine, but only in the presence of oxygen and in the absence of cyanide. 

These alkaloids are considered to be formed by the coupling of the iboga alkaloid catharanthine and the Aspidosperma alkaloid vindoline, both of them derived from tryptophan. The other parts of both alkaloids are derived from a secoiridoid (Cjo) unit, and strictosidine is the primary precursor of both alkaloid units (Section 2.9) [8]. Mangeney et al. [9] succeeded in the syntheses ofVLB andVCR by the coupling of catharanthine and vindoline. VLB can be oxidized under controlled conditions to VCR. 

Coronaridine subtype alkaloids are widely spread in Tabernaemontana. The iboga skeleton is particularly susceptible to oxidation at aminomethylenes C-3 and C-5 and at benzylic C-6. Very often, the fundamental compounds are accompanied by the oxidation products at these positions. 

Although the isolation of the principal alkaloid, ibogaine, of Taber-nanthe iboga was described at the turn of the present century (1), it was not until the early 1950 s that serious work on its structure was begun. It had been shown to contain a methoxy group and, by means of color reactions (19) and by measurement of its UV-spectrum, to be an indole (20), but it was not recognized to be a methoxyindole until permanganate oxidation was found to afford 5-methoxy-A-oxalylanthranilic acid (21). 

If the C-15, C-16 bond is oxidatively cleaved, the secodine skeleton results (the proposed progenitor of the Aspidosperma and the iboga systems) through alternative Diels-Alder type cyclizations to afford tabersonine and catharanthine. The bisindole alkaloids of Catharanthus roseus reflect the union of vindoline and catharanthine to afford anhydrovinblastine modification affords the clinically significant alkaloids, vinblastine (VLB) and vincristine (VCR Fig. 39). The alkaloids, particularly VCR, are important as anticancer agents and have led to the development of the semisynthetic derivatives vindesine and vinorelbine (Fig. 40). Synthetic approaches are available to join the monomeric precursors. The enzymatically controlled sequence of reactions from tabersonine to vindoline has been elucidated. 

Rearrangements of Iboga and Aspidosperma Types. It is possible to envisage the biological rearrangements of the monoterpene-tryptamine alkaloid skeleta as proceeding via a common intermediate (132), reversibly derivable, at least on paper (see below) from each of the skeletal types, providing that a structure at the correct oxidation level is chosen. Thus tabersonine (133) (aspidosperma). 

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