Indole alkaloids Aspidosperma group

Terpenoid indole alkaloids This group of alkaloids is very large and contains more than 3000 compounds. Three types of nucleus occur here the corynanthe, iboga, and aspidosperma ... 

The Ziegler group has described a creative approach to mitomycin derivatives and the related alkaloid FR-900482 that involves use of indoles as radical acceptors (Eq. 28) [62]. The key step involves cyclization of aziridinyl bromide 98 to 99 which was carried on to (+)-desmethoxymitomycin A. This reaction surely illustrates the unusual bond constructions that can be accomplished using free-radical chemistry. Interesting approaches to other indole alkaloid substructures have been reported as illustrated in Eqs. (29) [63] and (30) [64]. The former was developed in an approach to lysergic acid while the later is a model study for the synthesis of aspidosperma alkaloids. Neither of these interesting approaches has been brought to fruition. A synthesis of carbazomycin that involves an aryl radical cyclization for construction of the C3-C3a bond of an indole has also been described [65]. 

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...

The Aspidosperma alkaloids are a group of more than 100 monomeric and dimeric monoterpene indole alkaloids with aspidospermidine (228) representing a key member of the class and sometimes considered to be the parent [68]. Numerous total syntheses of this pentacyclic compound have been reported. Our own contributions in the area were prompted by the discovery of a new method for preparing indoles via a palladium-catalysed Ullmann cross-coupling reaction that proceeds especially efficiently at close to room temperature [69] and which we felt could serve as the centrepiece in developing a new synthesis of compound 228 and, in the longer term, syntheses of dimeric members of the indole alkaloid class such as the clinically significant alkaloids vinblastine and vincristine. 

Other groups of alkaloids that coincidentally have this ring structure will be discussed under better known groupings [e.g., the alkaloids of Aspidosperma (indole alkaloids. Chapter 34), Erythrina (benzylisoquinoline alkaloids. Chap-... 

Rauwolfia alkaloids a group of about 50 structurally related indole alkaloids firom the roots and rhizomes of various species of Rauwolfa, Aspidosperma and Corynanihe. All R. a. contain a -carbolene skeleton they are classified into 3 types 1. yohimbine (cory-nanthine), 2. ajmaline, 3. serpentine. The large number of R. a. is due to the existence of stereoisomers. Thus Rauwolfia contains seven stereoisomers of yohimbine. 

The monoterpenoid origin of the indole alkaloids has now been established. VIhile the Cp.io unit of the indole alkaloids is of mevalonoid origin, geraniol is a precursor of representative examples of the Corjynanthe, Iboga and Aspidosperma groups of bases which collectively account for the majority of indole alkaloids. 5 5... 

Isomunchnone dipoles generated by the cyclization of rhodium carbenoid intermediates with adjacent amido groups have also been shown to undergo cycloaddition with both electron-rich and certain heteroaromatic 7i-bonds. For example, the catalytic decomposition of diazoimide 12 provided dipole 13 which subsequently added across the indole 7i-bond to give a cycloadduct possessing the aspidosperma alkaloid skeleton (Scheme 4) (95JOC6258). 

The photo-Fries reaction of AT-acylindoles has been applied to the synthesis of alkaloids possessing the Strychnos, Aspidosperma, Schizo-zygane, and Eburnamine skeletons [37]. The key intermediate in these syntheses was the nine-membered lactam 12, which is prepared in 90% yield from photolysis of the AT-acylindole 13. It was demonstrated that this reaction proceeds via the unstable indolenine intermediate 14, which is intercepted by the amine side chain, as shown in Scheme 5. The high yield of this reaction is in part due to the fact that the acyl group in 13 is tethered so that it cannot rearrange to the indole 4 and 6 positions. 

Scheme 17.12. Stepwise decompositions of protonated Aspidosperma alkaloid occurring by either (a) stereochemical D ring cleavage yielding loss of acetamide neutral or (b) ion-dipole complex formation by A-benzyl bond cleavage of the protecting group of the indolic system decomposing into odd-electron product ions. (Adapted with permission from Ref 61.)...

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