Other Indole Alkaloids

In addition to the molecules described above, a number of other reports have appeared in the literature detailing applications of direct and/or long-range 2D NMR 

Wang and Ganesan [92], in the process of synthesizing a series of fumiquinazoline alkaloids, reported the extensive use of long-range H- i N 

Chemical shift data for analogs of 66 are collected in Table 14.4, while the chemical shifts for the one product, 67, for which they were reported are shown on the structure. The original report also contains chemical shift data for a number of synthetic intermediates to which the interested reader is referred. 

The authors also reported chemical shift assignments for one additional compound [92]. Refluxing the t-butyl substituted precursor of 66 in CH2CI2 with triphenylphosphine, iodine, and triethylamine led to the formation of the substituted p-carboline, 68 

Later in 2001, Clark and coworkers [97] reported the isolation and structure characterization of an indolopyridoquinazoline alkaloid, 3-hydroxyrutaecarpine, (75) from Leptothyrsa sprucei. This study was particularly interesting in that the authors reported the substructural fragments 76-78, which were assembled prior to the final determination of the structure of 75. Long-range and H- 

1 Structure and Solvent Effects on the and Shifts of Indoloquinoline Alkaloids 

In 2007, Marek and coworkers [57] reported a study of the assignment of the shifts of members of the indoloquinohne alkaloid family that have demonstrated activity in the control of the organism Plasmodium falciparum the most dangerous of the Plasmodium sp. responsible for causing malaria. Usefully, the authors reported the measured long-range couphngs for 

Chemical shifts are reported relative to liquid ammonia and all data were acquired in DMSO-d unless otherwise specified [57], 

The review by Marek and coworkers [57] also reported chemical shifts calculated using DFT methods with several different basis sets, which affords an interesting opportunity to contrast observed, neural network calculated, and DFT-calculated chemical shifts from a number of the alkaloids in this study (see Table 6). 

Dictyodendrin alkaloids have been described as the first telomerase inhibitors of marine origin and hence represent potential lead compounds in the quest for small molecule inhibitors of the tumor-marker enzyme. In a 2009 study, Fiirstner et al. [58] reported the synthesis of several members of the series, making use of FI—HMBC data. 

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J. Other indole alkaloids (including andranginine, adina bases, and cinchona... 

The structure of callichiline, apart from recognition of its chromo-phoric moiety which must include the carbonyl and methoxy groups, is practically unknown it has no W-methyl and is apparently not identical with any of the other indole alkaloids (about a dozen) with the same UV-spectra. If the functional group analyses are correct, biogenetic considerations would suggest that the formula be revised to C21H22-24N2O3. 

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... 

Melinonine G (flavopereirine) has considerable biogenetic interest because it lacks the two or three carbon atoms which in most other indole alkaloids are attached at the asterisked position (see XLIV). Thus, this alkaloid may be regarded as a partly degraded system or, on more recent views (67, 68), the three-carbon unit may never have been attached. 

Oxaline (143) was isolated in 1974 by Nagel et al. (183,184) from cultures of the toxicogenic fungus Penicillium oxalicum. The compound may be classified as an indole alkaloid, but it is one of the three indole alkaloids known at present that also contains an imidazole substituent the other indole alkaloids being roquefortine (144) and neoxaline (145). The structure of oxaline was deduced from physicochemical data and confirmed by single-crystal X-ray analysis. It has been suggested that in the biosynthesis of oxaline, nature makes use of the amino acids tryptophan and histidine (184). 

Aconitine and related diterpene alkaloids (A) veratridine, zygadenine, and related steroidal alkaloids (A) ajmaline, vincamine, ervatamine, and other indole alkaloids (AA) dicentrine and other aporphine alkaloids (AA) gonyautoxin (AA) paspalitrem and related indoles (AA) phalloidin (AA) quinidine and related quinoline alkaloids (AA) sparteine and related quinolizidine alkaloids (AA) saxitoxin (AA) strychnine (AA) tetrodotoxin (AA)... 

One other indole alkaloid, reminiscent in structure of the pseudophrynamines, has been isolated from amphibians, namely, chimonanthine 14) (XVII). Chimonanthine was accompanied in the dendrobatid poison-dart... 

Ehrlich s reagent reacts with a wide range of controlled substances and other indole alkaloids. A positive reaction does not therefore prove the presence of a specific drug. This is why it is necessary to carry out an additional confirmatory test. 

Deglucosylation of strictosidine, a key reaction in the formation of the many types of indole alkaloids, is carried out by a specific glucosidase, strictosidine-(3-D-glucosidase (SGD) (Fig. 2.9). The protein and cDNA have been isolated from C. roseus and a number of other indole alkaloid-containing plants of the Apocynaceae. The specific glucosidase is involved in an essential initial reaction that leads to a complex sequence of events and a series of highly reactive intermediates. When glucose is split off, the hemiacetal opens and exposes... 

Dyer et al. oxidized a furanoside derivative by the DMSO-DCC-pyridinium phosphate method, and Albright and Goldman applied the Pfitzner-Moffatt procedure successfully for oxidation of yohimbine and other indole alkaloids. Suscep-... 

Hydroxy-17-decarbomethoxy-16-dihydro-epiajmalicine (87), Q9H24N2O2, mp 185°C, is a new natural product encountered in the bark of Hunteria zeylanica, a plant endemic to Sri Lanka (78). Structural proof involved the semisynthesis of 87 by oxymercuration of corynantheal. Other indole alkaloids belonging to this class isolated from H. zeylanica included yohim-bol (88) and the new natural product epiyohimbol (89), C19H24N2O, mp 257°C, whose structures were confirmed by comparison with NaBfL reduction products of yohimbone. The fruits of Alstonia macrophylla have... 

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]. 

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. 

Other cell suspension cultures of Catharanthus roseus synthesize and accumulate substantial amounts of both serpentine (8) and ajmalicine (7). Serpentine (8), the principal alkaloid of some cell cultures of Catharanthus roseus, is derived from ajmalicine (7) in contrast to some other indole alkaloids, serpentine is located inside the vacuole (Deus-Neumann and Zenk, 1984 Zenk et al 1985). Serpentine... 

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