C. autumnale

To the best of our knowledge few natural (-)-allocolchicinoids have been reported. As mentioned above, natural (-)-allocolchicine 1 was isolated from C. autumnale [3,4] and C. kesselringii [5]. 3-Demethyl-allocolchicine 6, identified previously as the methyl ester of 2-demethylcolchicinic acid, was also isolated from the latter plant [5], Other natural allocolchicinoids, also named dibenzocycloheptylamines, have been reported. Colchibiphenyline 7 was isolated from Colchicum ritchii R. Br. [28] and (—)-androbiphenyline 8 from Androcymbium palaestinum (Boiss.) Bak. [29], C. ritchii [28] and Colchicum decaisnei Boiss. [30]. The latter plant also produces (-)-jerusalemine 9, (-)-salimine and (-)-suhailamine [30], though the exact structure of salimine was later questioned [31] and suhailamine had a reported structure identical to that of allocolchicine. 

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 is obtained from the autumn crocus, Col-chicum autumnale, or the glory lily, Gloriosa superba. C. autumnale was first introduced for the treatment of gouty arthritis in 1763 by Von Storck. 

Animal toxicity is primarily related to ingestion of the plant C. autumnale. Colchicine is available as a pesticide for burrowing animals. The estimated toxic dose for cows is lOgkg with fresh leaves or 2 or 3gkg with dried leaves. Symptoms may include gait disorders, hypersalivation, bloody vomitus, and diarrhea. Death within 72 h has occurred secondary to shock. It is only slightly toxic to cold-blooded and hibernating animals. 

A survey of Yugoslavian Colchicum species revealed the presence of colchicine in C. arenarium, C. autumnale, C. bartolini, C. doerfleri, C. kochii, C. latifolium, C. macedonicum, and C. visianii,178 Unripe seeds of Colchicum plants were found to contain 40 % less colchicine than fully ripe ones. 

It is a relatively recent observation that Colchicum species contain numerous chemical constituents of diverse chemical properties. Recognition of this fact has led to more efficient methods of isolation. In addition to neutral, phenolic, and basic alkaloids, 0. autumnale contains fatlike substances which are removed by a preliminary ligroin extraction of the pulverized, dry material. From such an extraction of the flowers of C. autumnale, Santavy and Herout (293) have isolated a paraffin, Ca7-28H5g 58, m.p. 58-60° an alcohol, CaaH450H, m.p. 66-67° and a phytosterol, m.p. 139-140°. Benzoic, salicylic, and 2-hydroxy-6-methoxybenzoic acids may be separated from the alkaloid mixture by virtue of their solubility in ether and aqueous base (294). The alkaloids themselves may be separated into neutral, phenolic, or basic fractions by standard extraction techniques. Pure alkaloids may be obtained from each fraction by fractional crystallization and chromatography on... 

The minor alkaloids occurring with C. autumnale are not always removed completely in the preparation of U.S.P. colchicine. Colchicine of this purity has been reported to be contaminated with Substance B (315) and Substance C (316). 

From the seeds of C. autumnale, Santavy and Tala (298) isolated trace amounts of this material, m.p. 212-214°, [aj —140° (chloroform). No analytical data were given, but polarographic evidence suggested the presence of a tropolone ring. 

The flowers of C. autumnale afforded trace quantities of a basic, glycosidio material, C27H33NO11, m.p. 310-314°, which was designated Substance M (303). The material contains three methoxyl groups and one acetyl function. Acetylation afforded a pentaacetate, m.p. 302-304°, [o]o —244° (chloroform). Preliminary tests indicated the absence of a tropolone ring. 

Substance 0 was obtained from the flowers of C. autumnale by chromatographic separation of the mother liquors from the crystallization of colchicine (303). The material, m.p. 254 256°, [a]o —144° (chloroform), contains four methoxyl groups and one acetyl function. A carbon-hydrogen determination was not reported, but on the basis of the methoxyl and acetyl determination, a molecular formula, CgjHjjNOe, was proposed. The tropolone ring appears to be absent. 

This compound, m.p. 196-198°, was isolated from the corms of C. autumnale (294). No analytical data were presented, but a tropolone ring was indicated by a positive ferric chloride test after hydrolysis with dilute acid. 

The actual pathway used in the biosynthesis of colchicine was initially clarified by the tracer experiments of Leete (6, 58-60), Battersby (61-64), and co-workers. Both C. autumnale and G. byzantium were used in these studies, and similar trends in incorporation of various potential precursors were obtained by both groups. The incorporation data are shown in Table VI and the degradation schemes used to identify individual carbon atoms or groups of atoms are summarized in Fig. 1. 

The incorporation C. autumnale) of 0-methylandrocymbine (CXVII R = CH3, tritium label in the OCH3 at carbon 2) and CXVIII (i C at carbon 6) into colchicine (15 and 10% incorporation, respectively) with no randomization of label indicated the general correctness of the proposed scheme. Multiple labeling experiments with synthetic CXVIII have confirmed many details of the biosynthesis. CXIX was incorporated into colchicine with no change in the ratio, proving that... 

The term colchicine originated from the area known as CoZc/hs near Black Sea. However, C. autumnale grows wild in Europe and Africa, while Gloriosa sp. is distributed in Africa and Asia including foothills of Himalayas, Burma, Indmiesia, Malaya, etc. Table 16.1 gives a summary of the occurrence of colchicine reported since 1946. 

C. autumnale is the first plant species exploited for the production of colchicine in vitro. Hunault [15] reported successful induction of callus culture of C. autumnale on Linsmaier-Skoog medium containing 2,4-dichlorophenoxyacetic acid (2,4-D) and kinetin. Growth and colchicine accumulation were increased in MS media supplemented with 20-mM ammonium and 40-mM nitrate. Addition of sulfate (S04 ) also increased the accumulation of colchicine in C. autumnale [16]. 

Both the corm and the seed of colchicum (C. autumnale Linn.) contain the alkaloid colchicine (0 4 per cent and 0 3 to 0 6 per cent respectively) and are assayed similarly, so they can be considered together. Only the corm is official in the B.P. 

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