Title: Colchicine
CAS Registry Number: 64-86-8
CAS Name: N-[(7S)-5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]acetamide
Molecular Formula: C22H25NO6
Molecular Weight: 399.44
Percent Composition: C 66.15%, H 6.31%, N 3.51%, O 24.03%
Literature References: A major alkaloid of Colchicum autumnale L., Liliaceae. Extraction procedure: Chemnitius, J. Prakt. Chem. [II] 118, 29 (1928); F. E. Hamerslag, Technology and Chemistry of Alkaloids (New York, 1950) pp 66-80. Structure: Dewar, Nature 155, 141 (1945); King et al., Acta Crystallogr. 5, 437 (1952); Horowitz, Ullyot, J. Am. Chem. Soc. 74, 487 (1952). Crystal structure: L. Lessinger, T. N. Margulis, Acta Crystallogr. B34, 578 (1978). Total synthesis: Schreiber et al., Helv. Chim. Acta 44, 540 (1961); Van Tamelen et al., Tetrahedron 14, 8 (1961); Nakamura, Chem. Pharm. Bull. 8, 843 (1960); Sunagawa et al., ibid. 9, 81 (1961); 10, 281 (1962); Scott et al., Tetrahedron 21, 3605 (1965); Woodward, Harvey Lectures, Ser. 59 (Academic Press, New York, 1965) p 31; Kotani et al., Chem. Commun. 1974, 300; D. A. Evans et al., J. Am. Chem. Soc. 103, 5813 (1981). Biosynthesis: Leete, Tetrahedron Lett. 1965, 333; Battersby et al., J. Chem. Soc. 1964, 4257; Hill, Unrau, Can. J. Chem. 43, 709 (1965). Tubulin-binding activity: J. M. Andreu, S. N. Timasheff, Proc. Natl. Acad. Sci. USA 79, 6753 (1982). Toxicity: S. J. Rosenbloom, F. C. Ferguson, Toxicol. Appl. Pharmacol. 13, 50 (1968); R. P. Beliles, ibid. 23, 537 (1972). Clinical evaluations in cirrhosis of the liver: M. M. Kaplan et al., N. Engl. J. Med. 315, 1448 (1986); D. Kershenobich et al., ibid. 318, 1709 (1988). Bibliography of early literature: Eigsti, Lloydia 10, 65 (1947). Monograph: O. J. Eigsti, P. Dustin, Jr., Colchicine in Agriculture, Medicine, Biology and Chemistry (Iowa State College Press, Ames, Iowa, 1955). Reviews: Fleming, Selected Organic Syntheses (John Wiley, London, 1973) pp 183-207; G. Lagrue et al., Ann. Med. Interne 132, 496-500 (1981); F. D. Malkinson, Arch. Dermatol. 118, 453-457 (1982). Comprehensive description: D. K. Wyatt et al., Anal. Profiles Drug Subs. 10, 139-182 (1981).
Properties: Pale yellow scales or powder, mp 142-150°. Darkens on exposure to light. Has been crystallized from ethyl acetate, pale yellow needles, mp 157°. [a]D17 -429° (c = 1.72). [a]D17 -121° (c = 0.9 in chloroform). pK at 20°: 12.35; pH of 0.5% soln: 5.9. uv max (95% ethanol): 350.5, 243 nm (log e 4.22; 4.47). One gram dissolves in 22 ml water, 220 ml ether, 100 ml benzene; freely sol in alcohol or chloroform. Practically insol in petr ether. Forms two cryst compds with chloroform, B.CHCl3 or B.2CHCl3, which do not give up their chloroform unless heated between 60 and 70° for considerable time. LD50 in rats (mg/kg): 1.6 i.v. (Rosenbloom, Ferguson); in mice (mg/kg): 4.13 i.v. (Beliles).
Melting point: mp 142-150°; mp 157°
pKa: pK at 20°: 12.35; pH of 0.5% soln: 5.9
Optical Rotation: [a]D17 -429° (c = 1.72); [a]D17 -121° (c = 0.9 in chloroform)
Absorption maximum: uv max (95% ethanol): 350.5, 243 nm (log e 4.22; 4.47)
Toxicity data: LD50 in rats (mg/kg): 1.6 i.v. (Rosenbloom, Ferguson); in mice (mg/kg): 4.13 i.v. (Beliles)
Use: In research in plant genetics (for doubling chromosomes).
Therap-Cat: Gout suppressant. Treatment of Familial Mediterranean Fever.
Therap-Cat-Vet: Has been used as an antineoplastic.
Keywords: Antigout. |