Colchicine and related alkaloid

Colchicum autumnale (autumn crocus) and other Colchicum species belong to the family known as the Colchicaceae, a proposed subdivision of the Liliaceae. They contain colchicine and related alkaloids. Other members of the Colchicaceae include Gloriosa species and Merendera species. C. autumnale (autumn crocus) is the traditional source of colchicine, which is covered in a separate monograph. 

Colchicine and Related Alkaloids.— The structure of speciosine (226) was deduced by spectroscopic methods and confirmed by synthesis from demecolcine and 2-bromomethylphenyl acetate. N-Formyldemecolcine is a new alkaloid found in Colchicum cornigerum ... 

The amide nitrogen of colchicine is not basic, and some have argued that colchicine is not a true alkaloid. However, as the precursors and the pathway leading to this compound are typical for those of alkaloids, colchicine is considered an alkaloid for present purposes. Although this compound is the best known of the group, more than 30 other tropolonic alkaloids occur in Colchicum autumnale and related plants (Capraro and Brossi, 1984). The physical constants and spectral data of colchicine and related alkaloids have been tabulated (Tojo, 1989). 

Alkaloids in the Plant by K. Mothes The Pyrrolidine Alkaloids by Leo Marion Senecio Alkaloids by Nelson J. Leonard The Pyridine Alkaloids by Leo Marion The Tropane Alkaloids by G. Fodor The Strychnos Alkaloids by J. B. Hendrickson The Morphine Alkaloids by Gilbert Stork Colchicine and Related Compounds by W. C. Wildman Alkaloids of the Amaryllidaceae by W. C. Wildman. ... 

Colchicine, pilocarpine, phytostigmine, echinulin and related alkaloids. 

Alkaloids are widespread in plants and include some very well-known poisons (notably coniine and strychnine), hallucinogens (morphine, cocaine and muscimol) and other potentially lethal compounds that are nevertheless used in medical practice (e.g. atropine, codeine, colchicine and morphine). As indicated by the preliminary snap-shot above, alkaloids typically have names ending in -ine and which are often related to the plant source or properties. Thus, morphine was named after Morpheus (the God of sleep) and coniine derives from Conium maculatum (hemlock), the plant used in the judicial murder of Socrates (399 BC). Various chemical tests for alkaloids are used as preliminary indicators of alkaloid presence in crude plant extracts. Finally, it should be noted that alkaloids can also exist as jVoxides of the alkaloid base. 

Caffeine and related purine alkaloids (AA) papaverine (AA) chelerythrine, sanguinarine, and related benzophenanthridine alkaloids (AA) colchicines (AA) infractine and related indole alkaloids (AA)... 

Even some or most of the common garden vegetables and fruits contain trace amounts of alkaloids as well as other potentially beneficial types of compounds. Our daily cups of coffee contain the alkaloid caffeine. Tobacco and some other plants contain the alkaloid nicotine, and there is ongoing research to determine beneficial medicinal properties for nicotine and related compounds, possibly even against cancer. The alkaloid colchicine is sometimes used as a treatment for gout, although it is a drug also used in horticulture to induce mutations in plant species. 

Phenethylisoquinoline alkaloids are classified into six major alkaloid groups based on structural differences, namely, simple 1-phenethyliso-quinoline (1), homomorphinandienone (2), bisphenethylisoquinoline (3), homoproaporphine (4), homoaporphine (5), and homoerythrina alkaloids (6). These alkaloids are related to the benzylisoquinoline alkaloids such as morphinandienone, bisbenzylisoquinoline, proaporphine, apor-phine, and erythrina alkaloids. Although colchicine and its derivatives also belong to the phenethylisoquinoline alkaloids group, these alkaloids are not included in this review as they have been reviewed earlier 1). 

Amaryllidaceae Alkaloids.—O-Methylnorbelladine (162) and vittatine (163) are implicated as intermediates in the biosynthesis of narciclasine (164). " Loss of the two-carbon bridge from the latter could plausibly occur by a retro-Prins reaction on 11-hydroxyvittatine (165) to give (166), as shown in Scheme 18, analogy for hydroxylation of (163) coming from the biosynthesis of the related alkaloid haeman-thamine.Strong support for this pathway to narciclasine (164) was obtained when it was shown that tritiated (165) was an efficient precursor for this alkaloid.It is to be noted that collapse of a similar j8-hydroxy-amine is proposed for the biosynthesis of colchicine. 

Investigation of colchicine, the major alkaloid of Colchicum and related genera, and its congeners has attracted a great amount of interest for many years. The long-established use of colchicine in the... 

The policy adopted in this ninth volume of The Alkaloids is once again to furnish a comprehensive annual survey of the alkaloid literature. As a result of unavoidable omissions in the eighth volume, a two-year coverage is provided of tropane alkaloids and, within the isoquinoline group (Chapter 8), of the chemistry of emetine and related bases, dibenzopyrrocolines, benzophenanthridines, and colchicine. The chapter on Miscellaneous Alkaloids also surveys the literature of the period July 1976— June 1978 purines are no longer included. 

Their occurrence is limited to the Liliaceae, e. g., Col-chicum, Kreysigia, anAAndrocymbium species (see table). They are readily soluble in water, chloroform, and ethanol. Colchicine is one of the few natural tropolone derivatives, see, e. g., fomentariol. It occurs together with other, structurally related alkaloids (colchamine, colchicoside, colchiceine, colchiciline, colchifoline) in meadow saffron (autumnal crocus, naked lady, Col-chicum aummnale). Colchicine is a highly potent mi-... 

The approximately 100 alkaloids of this series occur in the family Amaryllidaceae. This family is considered closely related to the Liliaceae and some taxonomists (e.g., Cron-quist, 1981) have merged the two into one large family. The alkaloids of the Amaryllidaceae are similar to colchicine and other related alkaloids of the Liliaceae in that both phenylalanine and tyrosine are involved in their synthesis. All Amaryllidaceae alkaloids, however, are derived from a single intermediate, norbelladine (4). The three major structural types are found at times in individuals of the same species. 

The observation that the aromatic ring of phenylalanine is incorporated into the mesembrine system via phenylpropanoid intermediates, when considered in conjunction with the demonstrated role involving the intact incorporation of iV-methyltyramine, led to the investigation of Ar—C3—N—C2—Cg compounds as precursors. This possibility seemed attractive because precedent exists for the utilization of such compounds in the phenethyltetrahydroisoquinoline alkaloids and related bases, such as colchicine, where experimental data has shown that these compounds are biosynthesized from a phenylalanine-derived Ar—C3 fragment and tyrosine-derived Cg—C2—N unit (75). Such a scheme seemed to possess a further advantage in that utilization of an Ar—C3—N—C2—Cg unit allows the construction of a general biosynthetic scheme (see Scheme 45) which encompasses all extant structural classes of Sceletium alkaloids. 

Actually there are no good definitions of alkaloids (Bate-Smith and Swain, 1966) since each one is either too narrow or too broad. Even in the restricted Winterstein and Trier definition, at least five alkaloid families exist that can be derived from different amino acids consequently, there is a need to establish the proper biosynthetic pathways to permit the application of the alkaloid character to chemotaxonomy, It has been mentioned above that canadine (berberidine) may be found in plants of six partially unrelated botanical families. This fact is not surprising when considered in relation to the biochemical investigations of canadine biosynthesis. Many reactions are necessary to convert tyrosine into canadine consequently, one might even wonder why the distribution of this alkaloid is so limited. In contrast, other plants (and even some that produce canadine) can produce many alkaloids that are derived from tyrosine but have a marked difference in structure. Tyrosine serves as the key precursor of alkaloids of the isoquinoline type, but other types of alkaloids, such as colchicine and the Amaryllidaceae and the Erythrina alkaloids, may be synthesized from this amino acid. The nucleus of an alkaloid molecule can arise from different precursors thus the indole nucleus in Erythrina alkaloids arises from tyrosine, while in brucine it comes from tryptophan (Figure 1.5). The alkaloids cinchonamine and cinchonine differ in that cinchonamine has an indole nucleus, while cinchonine (like quinine) has a quinoline nucleus however, they exist in a precursor-product relationship (that is, the quinoline type is derived from the indole type in a one-step reaction). 

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