7546. Podophyllotoxin

Nomenclature

CAS number: 518-28-5
(5R,5aR,8aR,9R)-5,8,8a,9-Tetrahydro-9-hydroxy-5-(3,4,5-trimethoxyphenyl)furo[3′,4′:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one; 1-hydroxy-2-hydroxymethyl-6,7-methylenedioxy-4-(3′,4′,5′-trimethoxyphenyl)-1,2,3,4-tetrahydronaphthalene-3-carboxylic acid lactone; podophyllinic acid lactone; podofilox; Condyline (Nycomed); Condylox (Oclassen); Wartec (Kabi); Warticon (Perstorp).
C22H22O8; mol wt 414.41.
C 63.76%, H 5.35%, O 30.89%.

Description and references

Precursor of antineoplastics etoposide, teniposide, q.q.v. Found in the rhizomes of North American Podophyllum peltatum L., Podophyllaceae: V. Podwyssotski, Arch. Exp. Pathol. Pharmakol. 13, 29 (1880); also in P. emodi Wall.: von Wartburg et al., Helv. Chim. Acta 40, 1331 (1957); in Juniperus virginiana L., Cupressaceae: Kupchan et al., J. Pharm. Sci. 54, 659 (1965). Structure and absolute configuration: Schrecker, Hartwell, J. Org. Chem. 21, 381 (1956). Crystal structure: T. J. Petcher et al., J. Chem. Soc. Perkin Trans. 2 1973, 288. Synthesis: Gensler, Gatsonis, J. Am. Chem. Soc. 84, 1748 (1962); T. Kaneko, H. Wong, Tetrahedron Lett. 28, 517 (1987). Asymmetric total synthesis: R. C. Andrews et al., J. Am. Chem. Soc. 110, 7854 (1988); E. J. Bush, D. W. Jones, Chem. Commun. 1993, 1200. Toxicity data: F. S. Phillips et al., Fed. Proc. 7, 249 (1948). ELISA determn in plants: K.-J. Yoo, J. R. Porter, J. Nat. Prod. 56, 715 (1993). Clinical evaluation for treatment of genital warts: A. Lassus, Lancet 2, 513 (1987); K. R. Beutner et al., ibid. 1, 831 (1989). Review of early literature: Hartwell, Schrecker in Fortschr. Chem. Org. Naturst. 15, 98-121 (1958). Review of chemistry and antineoplastic activity: I. Jardine, Anticancer Agents Based on Natural Product Models, J. M. Cassady, J. D. Douros, Eds. (Academic Press, New York, 1980) pp 319-351. Review of syntheses: R. S. Ward, Synthesis 1992, 719-730. Review: D. L. Sackett, Pharmacol. Ther. 59, 163-228 (1993).

Chemical structure

Properties

Solvated crystals. mp 114-118° (effervescence). Several polymorphic modifications. After drying: mp 183.3-184.0°. [α]D20 -132.7° (chloroform). Soly in water at 23°: 120 mg/l. Sol in alcohol, chloroform, acetone, warm benzene, glacial acetic acid. LD50 in rats (mg/kg): 8.7 i.v.; 15 i.p. (Phillips).

Derivative

Podophyllotoxin-β-d-glucoside.
C28H32O13; mol wt 576.55.
C 58.33%, H 5.59%, O 36.08%.

Properties

Hygroscopic amorphous white flakes, mp 152-154°. [α]D20 -76.4° (c = 0.576 in methanol); [α]D20 -117.0° (c = 0.668 in pyridine).

Derivative

Picropodophyllin.

Nomenclature

CAS number: 477-47-4
Picropodophyllinic acid lactone.
C22H22O8; mol wt 414.41.
C 63.76%, H 5.35%, O 30.89%.

Description and references

Found in resin podophyllum, a dried alcoholic extract of Podophyllum peltatum L., Berberidaceae but not in the fresh plant. 5aS-Isomer of podophyllotoxin. Isoln from resin podophyllum: Sp"ath et al., Ber. 65, 1545 (1932). Structure: Schrecker, Hartwell, J. Am. Chem. Soc. 76, 752 (1954). Synthesis: Gensler, Wang, J. Am. Chem. Soc. 76, 5890 (1954); Gensler et al., ibid. 82, 1714 (1960).

Properties

Crystals from acetone. Irritates the skin. mp 214°. Higher-melting modification from abs ethanol, mp 228°. [α]D20 +9.4° (c = 0.7 in chloroform). Soly in water at 25° ≈100 mg/l. Fairly sol in chloroform, hot ethanol, acetic acid, acetone, dil caustic; less sol in benzene, ether, carbon tetrachloride, propylene glycol. Practically insol in petr ether.

Therapeutic Category

Antiviral (topical).

Keywords

Antiviral