A-Peltatin

The lignan constituents of the two roots are the same, but the proportions are markedly different. The Indian root contains chiefly podophyllotoxin (Figure 4.21) (about 4%) and 4 -demethylpodophyllotoxin (about 0.45%). The main components in the American root are podophyllotoxin (about 0.25%), p-peltatin (about 0.33%) and a-peltatin (about 0.25%). Desoxypodophyllotoxin and podophyllotoxone are also present in both plants, as are the glucosides of podophyllotoxin, 4-demethylpodophyllotoxin, and the peltatins, though preparation of the resin results in considerable losses of the water-soluble glucosides. 

A limited clinical trial of podophyllotoxin and a co-occurring lignan, a-peltatin, was carried out in the early 1950s, but although some short-lived responses were observed, the general toxicity of the two compounds precluded further studies. At about the same time (1954), the Swiss pharmaceutical company Sandoz embarked on a programme of chemistry directed towards the... 

Prisms from abs ethanol. Irritates the skin, Dec 238-241 (slight sintering begins at 234 ). [ ] — 122.9 (c = 0.578 in chloroform). Somewhat less sol than a-peltatin. Soly in water at 23° 13 mg/liter. 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. 

Considerable progress has also been made in elucidating the biosynthetic pathway leading to the podophyllotoxin series (scheme 2) [38,39]. Dewick et al. have shown that demethylyatein (15a) and yatein (15b) are precursors of demethylpodophyllotoxin (18a) and podophyllotoxin (18b) respectively. Furthermore, 4 -demethyl-deoxypodophyllotoxin (16a) and deoxypodophyllotoxin (16b) undergo aromatic hydroxylation to yield a-peltatin (17a) and p-peltatin (17b) respectively. They have also shown that (-)-matairesinol (13) is efficiently incorporated into 4 -demethylpodophyllotoxin (18a), podophyllotoxin (18b), a-peltatin (17a) and p-peltatin (17b). These facts have been interpreted as indicating that matairesinol is a common precursor of both the 3,4,5-trimethoxyphenyl and 4-hydroxy-3,5-dimethoxyphenyl series. 

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