Podophyllotoxin type lignans

Nur-e-Alam M, Yousuf M, Qureshi S, Baig I, Nasim S, Atta-ur-Rahman., Choudhary MI (2003) A novel dimeric podophyllotoxin type lignan and a new withanolide from Withania... 

In conclusion, two kinds of 1-hydroxyphenyltetralin-type lignans, epipodophyllotoxin (12) and podophyllotoxin (11), were obtained from desoxypodophy-llotoxin (3), which is available in large quantities from the seeds of Hernandia ovigera L.. 

The lignans are a large group of plant phenolics, biosynthesized from the union of two phenylpropane molecules e.g., both matairesinol (Centaurea species, family Asteraceae) and podophyllotoxin Podophyllum peltatum, family Berberidaceae) are formed from the phenylpropane coniferyl alcohol. Lignans are essentially cinnamoyl alcohol dimers, though further cyclization and other structural modifications result in various structural types, e.g. dibenzylbutyrolactone and epoxy lignan. 

The first chemical constituent was isolated from podophyllin in 1880 and named podophyllotoxin (97). A structure was proposed in 1932 and after some fine-tuning (98) was shown to be the lignan (60). As might be expected, the crude resin contains a variety of chemical types, including the flavonols quercetin and kaempferol (99). Although these other constituents undoubtedly have biological activity, it is the lignans that have received most attention and to which we shall devote the remainder of this section. 

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... 

It is not possible in this article to give detailed consideration to the various physiological activities of lignans. Fortunately, a comprehensive review has recently appeared. Most of the known types of activity of lignans are listed in Table I. Although the list looks large it is, in fact, minimal. The activity one finds is a function of the activity one looks for, and no series of lignans has ever been comprehensively tested. Podophyllotoxin and its... 

---