Process for preparing pure podophyllotoxin

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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C07D30777

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053150163

ABSTRACT:
A process for preparing crystalline, anhydrous podophyllotoxin from a podophyllotoxin product comprises dissolving the product in a non-aromatic and non-halogenated solvent which has a boiling point at atmospheric pressure not exceeding 130.degree. C., and which contains at the most about 1% v/v of water, cooling the solution to precipitate crystals of podophyllotoxin, isolating the crystals and drying them at a temperature which during the drying procedure is increased but is always such that it is below the temperature at which the crystals sinter or melt, the drying being continued until the melting point is in a range of 183.degree.-184.degree. C. and the residual amount of solvent is at the most 500 ppm. When the starting material contains complexed or adsorbed organic solvent, an initial azeotropic evaporation treatment is performed to remove this solvent. The yield of pure podophyllotoxin is greatly increased by adding water to the crystallization mixture.

REFERENCES:
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patent: 5057616 (1991-10-01), Jennings et al.
Beutner et al., "Treatment of Genital Warts", Seminars in Dermatol., vol. 9, Jun. 1990, pp. 148-151.
Issell, "The Podophyllotoxin Derivatives VP16-213 and VM26", Cancer Chemother Pharmacol, vol. 7, 1982, pp. 73-80.
Buchardt et al., "Thermal Chemistry of Podophyllotoxin in Ethanol and a Comparison of the Cytostatic Activity of the Thermolysis Products", Journal of Pharmaceutical Sciences, vol. 75, No. 11, Nov. 1986, pp. 1076-1080.
Schrecker, et al., "Components of Podophyllotoxin", XVIII. Polymorphic Modifications of Podophyllotoxin, Journal Org. Chem., vol. 21, 1956, pp. 288-291.
Andersen, et al., "Inclusion Complexes with Podophyllotoxin, Structural Characterization and Chiral Recognition", J. Chem. Soc., Perkin Trans., vol. 2, 1990, pp. 1871-1979.
Dunstan, et al., "A Chemical Investigation of the Constituents of Indian and American Podophyllum (Podophyllum emodi and Podophyllum peltatum)", J. Chem. Soc., vol. LXXIII, 1898, p. 209.

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