Indole alkaloids, class

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

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. 

The neutral enamine cascade product 6 is hydrolyzed to restore the carbonyl functionality, return the catalyst, and deliver the desired intermediate product 7 in good yield (85%) and excellent selectivity (99% de and 99% ee). Subsequently, the cascade product can be transformed to enf-dihydrocorynantheol in a Wit-tig/reduction/hydrogenation sequence. The final product is obtained in 38% yield over four steps as the antipode of the natural product, which belongs to the archetypal indole alkaloid class of corynantheines that display attractive antiparasitic, antiviral. 

The ninth type, tacaman (class III skeleton) has been added by Verpoorte and van Beek in order to account for the isolation of a few tacamines (see below), new indole alkaloids which until now were found only in Tabernaemontana eglandulosa. 

This overall biosynthetic scheme is summarized in Scheme 7, and it is well to remember that C. roseus is almost alone as a plant in which this whole pathway can be viewed in its entirety, for most indole alkaloid-containing plants produce only one or two of the major alkaloid classes, and not all four. In addition, C. roseus is without doubt the most economically important of the indole alkaloid-containing plants, and thus studies were, and continue to be, driven by the goal of increasing the availability of the commercially significant alkaloids ajmalicine (39), vinblastine (1), and vincristine (2). 

Synthesis of the anti-arrhythmic drug ajmaline from Rauvolfia plants, an efficient source of several alkaloid types used in therapy, represents an even more advanced study of the total enzymatic synthesis of terpenoid indole alkaloids. Ajmaline is a class I anti-arrhythmic alkaloid because of its activity as heart muscle sodium channels antagonist [35],... 

Vinblastine (4 in Chart 1) and its congeners are dimeric indole alkaloids derived from Catharanthus (Vinca) roseus. Nowadays, the vinca alkaloids constitute an important class of widely and successfully used anticancer agents that inhibit tubulin polymerization [8],... 

Just as terpenes could be viewed as being formed from isoprene units, alkaloids can be viewed as being derived from amino acids. Four amino acids give rise to important classes of alkaloids. As shown in Table 28.1, the pyrrolidine alkaloids are derived from the amino acid ornithine (not one of the 20 standard amino acids), the piperidine alkaloids from lysine, the isoquinoline alkaloids from tyrosine, and the indole alkaloids from tryptophan. 

Indole alkaloids represent a fundamental class of natural products and have important biological properties. Therefore, a large number of different methods for indole... 

A major class of amphibian alkaloids was recently discovered in frogs of the myobatrachid genus Pseudophryne (86,119). These represent the unidentified indolic compounds first noted by Erspamer and co-workers in 1976 (169). Isolation of two of these indole alkaloids from partially purified extracts of Pseudophryne coriacea allowed structure elucidation of pseudophrynaminol (XIV) and pseudophrynamine A (XV) by nuclear magnetic resonance spectral analysis (119). Methoxide cleavage of pseudophrynamine A yielded pseudophrynaminol and a methyl ester... 

---