Alkaloids chemical classification

As with most attempts at chemical classification, some alkaloids do not fall satisfactorily into any of the preceding groups, and others can be classified under more than one group. 

Using this type of chemical classification is useful, and such a classification is used predominantly in this book. However, this approach also encounters some challenges. For example, autumnaline and (S)-reticuline are typical isoquinoline alkaloids, whereas colchicine and morphine, which... 

Presently, alkaloids are classified into three main categories as shown in Fig. 8.2 [6]. This chemical classification of alkaloids is universally adapted and mainly depends on the type of heterocyclic ring structure present (Fig. 8.3). Alkaloids are further classified according to the amino acids (or their derivatives) from which they originate (Fig. 8.4) [6]. The most important classes are derived from the amino acids, ornithine and lysine, or from the aromatic amino acids, phenylalanine and tyrosine, or from tryptophan and a moiety of mavelonoid origin. A number of alkaloid-based compounds are also derived from anthranilic acid or from nicotinic acid. 

The idea that alkaloids are without value for taxonomic purposes was firmly upheld until about a decade or two ago because organic chemists and plant taxonomists had difficulty communicating with each other. Around the turn of the century, the chemical classification of alkaloids was based on readily distinguishable degradation products, and the following classes... 

The bisbenzylisoquinoline alkaloids are represented by over 225 different compounds which have been isolated from plants in 14 different plant families (Guha et al. 1979, Schiff Jr. 1983). It is the purpose of this presentation to review the distribution, chemical classification and major reactions of importance in structure elucidation of these alkaloids. In addition, a tabular summary of new alkaloids isolated and identified in the last several years will be presented. 

Thus, cholinergic receptor classification can be considered in terms of three stages of development. Initially, Dale [2] distinguished nicotinic and muscarinic receptor subtypes with crude alkaloids. Then, chemical synthesis and structure-activity relationships clearly revealed that nicotinic and muscarinic receptors were heterogeneous, but chemical selectivity could not come close to uncovering the true diversity of receptor subtypes. Lastly, analysis of subtypes came from molecular cloning, making possible the classification of receptors on the basis of primary structure (Fig. 11-2). 

In this series, three earlier reviews on carbazole alkaloids were published by Kapil (1), Husson (2), and Chakraborty (3) in the Volumes 13,26, and 44, respectively. The present chapter introduces a new classification of carbazole alkaloids and summarizes the recent synthetic efforts. The nomenclature of carbazole alkaloids used in this review is that of Chemical Abstracts. As shown in Scheme 1.1, the conventional tricyclic ring system of carbazole 1 is denoted by A, B, and C, and the numbering starts from ring A. The term carbazole generally refers to a 9H-carbazole. 

The presence of pavines and isopavines has been used to provide assistance for taxonomic classifications, and to determine intergeneric and phylogenic relationships in the genera Papaver and Argemone. The results of extensive chemical research on Papaver species demonstrated that morphologically distinct sections are also chemically distinguishable by virtue of their alkaloidal profile (170). Out of nine well-defined sections of Papaver, the Section Scapiflora, which displays... 

In an attempt to use the chemical constituents of the Quararibea-Matisia complex as an aid in their classification, these simple testing procedures were applied to 20 Central American samples representing either of the two genera. The highly odorous furanones, as well as positive alkaloid tests, were noted in 13 of these samples and absent in seven. The suggestion is that the former represent... 

There are several peptide alkaloids which do not fit the above described classification, namely, pandamine (56), pandaminine (57), hymenocardine (58), and lasiodine-A (59). The determination of their structures has already been referred to (3, 4) and is briefly outlined here. It was largely consequent upon chemical degradation in part because the mass spectral fragmentation patterns had not been worked out and in part because such analyses of the alkaloids or their derivatives do not, or only partly, lend themselves to the study of such fragmentation schemes as are described in Section VII. 

The family of the Papaveraceae includes 31 genera and approximately 700 species (2). The alkaloids contained therein are derivatives of the 1-benzyltetrahydroisoquinoline alkaloid reticuline (1). For the classification and chemical data of the described alkaloids (3-5) as well as for the pharmacodynamic properties of morphine and codeine (6, 7) see reviews. Some pharmacological aspects have been dealt with by Shamma (5) and Krueger et al. (8). 

In a very recent examination of C. manii Hook., a new antitumor alkaloid was isolated but found to be structurally unrelated to the usual Cephalotaxus alkaloids. In view of the chemical results the botanical classification of the plant is being reexamined (96). 

Using a set of 40 naphthyl-isoquinoline alkaloids, Bringmann and Rummey (56) compared two different methods of generating alignments automatically. Typically, data are divided into a training set used to optimize the parameters of the model and a test set that does not influence the model in any way but is used for evaluation of the predictive abilities of the final model. In this study, all available compounds were used for model development, and given that the researchers synthesized and tested new compounds on a continuous basis, the test set consisted of newly synthesized chemical compounds. When seven newly synthesized compounds were evaluated and predictions were made, a poor correlation was seen between actual and predicted IC50 values (r 0.279). If instead, the results are evaluated as a classification of active or inactive, five of the seven structures are predicted correctly. 

Because of the difficulties associated with the Delphinium classification, the diterpene alkaloid content was assessed as an aid to determining the chemical taxonomic diversity of the toxic larkspur species [59]. Plant samples were collected from 18 different locations in five western states in the US. The crude methanolic extracts were analyzed for diterpene alkaloids using FI-ESI-MS. The data from the individual ESI mass spectra were statistically analyzed using canonical discriminant analysis and analysis of variance. In brief, the sample (100 mg) was extracted by mechanical shaking at room temperature with methanol (5mL) for 16h. Reserpine (500 p.g) was added as an internal reference standard and the sample mixed for 5 min and then centrifuged. An aliquot (30 jxL) of the supernatant was then diluted with of 1 1 methanol/1 % acetic acid (1.0 mL) and an aliquot (20 jjlL)... 

The classification of the larkspur species using the chemical alkaloid profiles was in complete agreement with the molecular genomic data [63]. 

Less commonly, NMBAs are classified based on their chemical nature to include namral alkaloids and their congeners (e.g. d-tubocurarine), aminosteroids (e.g. cisatracurium, vecuronium) and benzylisoquinolines (e.g. succinylcholine). This classification scheme also relates to mechanism of actions and associated effects. 

In a space of six years the number of alkaloids isolated in this family has swelled from the 15 reported by Cook and Loudon in Chapter 11, Volume II, to more than 70. During this period chemical studies have established the structures of approximately half of the alkaloids, and many of the ambiguities and eontradictions of the earlier literature have been clarified. The previous classification of all AmaryUidaceae alkaloids in the phenanthridine group has proved to be an oversimplification... 

The details of the classifications and chemical structures of four types of natural phthalides are illustrated in Figs. (2-6). Most of the isolated natural phthalides belong to the 3-substituted phthalide type, which accounts for about 61% of the total known naturally occurring phthalides, and of these, non-alkaloid phthalides constitute the most important subtype due not only to their abundance in nature (75 compounds identified) but also their extensively reported pharmacological activities. The pharmacological activities of individual phthalides are discussed in the following Biological Activity Section. 

The alkaloids discussed under this heading do not lend themselves readily to classification with those of any of the previous groups. The chemical constitution of many of them has not yet been determined and, in many cases, the uterine actions have not been studied extensively. None of these alkaloids has attained clinical importance as an oxytocic. 

Forty four alkaloids were newly isolated from the 22 lupin plants and the structures were elucidated in our recent study. The structures were determined by spectroscopic investigations, in particular, by extensive 2D-NMR experiments in the recent works, and by chemical transformation. Biosynthetic pathways are also proposed, in some cases, by the preparation of isolated enzymes and by in vitro cell culture system. Chemotaxonomic relationships of the lupin plants are discussed based on the structural classification of alkaloids. 

There is no uniform classification for the A. In the literature divisions according to origin (examples Aconitum, Amaryllidaceae, Aspidosperma, cactus, Catharanthus, Cephalotaxus, Cinchona, coca, Corydalis, curare, Dendrobates, ergot, Erythrina, Iboga, Lycopodium, Maytenus, opium, Rauvol-fia, Senecio, Strychnos, tobacco, Vinca alkaloids, salamander, Solanum, Veratrum steroid alkaloids) in addition to divisions according to chemical structure (examples aporphine, benzylisoquinoline, bis-benzylisoquinoline, berberine, carboline, diterpene, inudazole, indole, indolizidine, isoquinoline, lupinane, macrocyclic, morphine, peptide, / -phenyl-ethylamine, piperidine, purine, pyridine, pyrrolidine, pyrrolizidine, quinoline, quinolizidine, quinucli-dine, spermine, spermidine, steroid, terpene, tro-pane, tropolone alkaloids) are used. 

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