Alkaloids Structure and Pharmacological Properties

Jerome Kluza, Philippe Marchetti, Christian Bailly 7.1 

Modem Alkaloids Structure, Isolation, Synthesis and Biology. Edited by E. Eattorusso and O. Taglialatela-Scafati Copyright 2008 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31521-5 

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The Erythrophleum alkaloids represent a clearly defined class, both as regards their chemical structure and pharmacological properties. They are alkamine esters of monocarboxylic acids of the diterpene series and possess remarkable cardiac activity of the digitalis type coupled with very intense local anesthetic action. 

Alkaloids thus represent one of the largest groups of natural products, with over 10,000 known compounds at present, and they display an enormous variety of structures, which is due to the fact that several different precursors find their way into alkaloid skeletons, such as ornithine, lysine, phenylalanine, tyrosine, and tryptophan (38-40). In addition, part of the alkaloid molecule can be derived from other pathways, such as the terpenoid pathway, or from carbohydrates (38-40). Whereas the structure elucidation of alkaloids and the exploration of alkaloid biosynthetic pathways have always commanded much attention, there are relatively few experimental data on the ecological function of alkaloids. This is the more surprising since alkaloids are known for their toxic and pharmacological properties and many are potent pharmaceuticals. 

The most important natural sources of minor tobacco alkaloids are from Nicotiana species, and at least eight minor tobacco alkaloids are shown in Figure 1. Since the chemical structures and physical properties of these minor tobacco alkaloids are similar to that of nicotine, some of them are shown to exhibit similar pharmacological activities as those of nicotine, although with a much lower potency. Table 2 shows their relative molar potency in some pharmacological systems. When nornicotine or anabasine was applied to the cat cervical ganglion, initial stimulation was followed by paralysis. On the autonomic ganglion and neuromuscular junction, nornicotine is only one-fifth to one-tenth as active as nicotine. Both nornicotine and anabasine have vaso-depressor action and affect the respiratory system. 

Structure Activities and Pharmacological Properties of the Opium Alkaloids... 

The tropane alkaloids are a well-recognized group of structurally related natural products. Long before elucidation of the structures, the mydriatic and anesthetic action of several compounds was exploited (6). The very extensive literature covering the pharmacological properties of the tropane alkaloids will be considered only briefly in this chapter. Readers with a deeper interest in the subject are referred to other publications (7-14) and to the references given in Section VII. 

Bisbenzylisoquinoline alkaloids. Comprehensive tabulation of literature for 1978-1981 (Chemical Abstracts Volumes 88-95), with 164 references. Covers structure revisions, additional (mainly spectral) data on known alkaloids, new sources of known alkaloids, structures, properties, summarized confirmatory reactions of new alkaloids, and biosynthetic evidence. Alkaloids are tabulated by botanical sources and pharmacological activity. A section on methods (CD, luminescence spectra, specific rotation, TLC) is included. 

II. Structure, Pharmacological, and Toxicological Properties of the Papaveraceae Alkaloids... 

Many Erythrina alkaloids possess curare-like action. Alkaloidal extracts from different parts of Erythrina species have been used in indigenous medicine, particularly in India (176). Many pharmacological effects, including astringent, sedative, hypotensive, neuromuscular blocking, CNS depressant, laxative, and diuretic properties, have been recorded for total alkaloid extracts, although not all these properties can be associated with the ery-thrinane structure alone (38, 177, 178). 

The diterpenoid alkaloids, isolated mainly from Aconitum and Delphinium species (Ranunculaceae), have been of great interest since the early 1800s because of their pharmacological properties. Extracts of Aconitum species were used in ancient times for treatment of gout, hypertension, neuralgia, rheumatism, and even toothache. Extracts have also been used as arrow poisons. Some Delphinium species are extremely toxic and constitute a serious threat to livestock in the western United States and Canada. Delphinium extracts also manifest insecticidal properties. In the last 30 to 40 years, interest in the diterpenoid alkaloids has increased because of the complex structures and interesting chemistry involved. 

Alkaloids of Aconitum kusnezojfii Reichb.—Researchers in the Peoples Republic of China have reported studies on the alkaloids of Aconitum kusnezojfii Reichb. that had been collected in Inner Mongolia.29 The pharmacological effects of extracts of these plants were studied in several animal systems.30 The known alkaloids aconitine (55), mesaconitine (56), hypaconitine (57), and deoxyaconitine (79) were identified on the basis of comparison of their physical and chemical properties with those of authentic samples. In addition, a new base, beiwutine (C33H45N012 m.pt 196—198 °C), was reported. This base formed a perchlorate salt (m.pt 255—257 °C) and a tetra-acetate derivative (m.pt 242—244 °C). From the H and 13C n.m.r., i.r., and mass-spectral data, structure (80) was proposed for beiwutine. 

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