Lactones podophyllotoxin

The resin product obtained by extraction of the dried roots and rhizomes of the North American plant Podophyllum peltatum L. (the American mandrake or mayapple) and of the related Indian species Podophyllum emodi Wall. Ex Royle is known as podophyllin and has long been known to possess medicinal properties. The major active substance in podophyllin is the lignan lactone podophyllotoxin (7) although a variety of other lignans and lignan glycosides have also been isolated from podophyllin. ... 

Another anti-cancer agent in clinical use is podophyllotoxin (3-59) this has an aryl tetrahydronaphthalene lignan lactone skeleton, and demonstrates potent tubulin-binding, anti-mitotic properties (Scheme 3.16) [30]. The Sherburn group [31] prepared this molecule by a tris(trimethylsilyl)silane promoted conversion of thionocarbonate 3-55 into the lactone 3-58, which proceeded with a yield of 38 %. As intermediates, the radicals 3-56 and 3-57 can be assumed. 

Podophyllotoxin 1-0-glucoside (= Podophyllinic acid lactone 1-0-glucoside) (lignan)... 

There has been much interest in the synthesis of lignan lactones of the aryl tetralin type, induced by the antitumour activity of podophyllotoxin relatives, and some short oxidative routes into the series have been pursued. In a typical reaction, in which both Cp—Cp and Cp—Car couplings occur, the cinnamyl cinnamate (297) was treated for 30 s with chromium trioxide-fluoroboric acid in acetonitrile. Three tetracyclic products were obtained, the lactones (298 19%) and (299 7%), and ( )-isopodophyllotoxone... 

Fig. (10). Modifications of podophyllotoxin involving opening of the lactone D-ring and introduction of unsaturation in the C-ring...

Fig. (11). Modifications of podophyllotoxin involving the A-ring and using the picropodophyllotoxin lactone configuration...

Podophyllotoxin is an aromatic lactone that arrests the metaphase activity in the DNA synthesis. 

Compounds structurally related to podophyllotoxin often have antimitotic activity. They arrest cultured cells at metaphase and bind to purified tubulin preparations. The lactone ring of podophyllotoxin is involved in this binding (MacRae and Towers, 1984). 

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