Deoxypodophyllotoxin

Podophyllotoxin (Fig. 4), a non-alkaloid toxin lignan, is a laxative, anti-tumor and antirheumatic agent. Cell cultures of Linum flavum were shown to be able to convert deoxypodophyllotoxin, a lignan isolated from Anthriscus sylvestris, into podophyllotoxin. ... 

Dysosma pleiantha (Hance) Woodson Pa Jiao Lian (rhizome) Podophyllotoxin, astragalin, peltatin, etoposide, hyperin, deoxypodophyllotoxin.33 Treat condyloma acuminata, exophytic warts. 

China Anthriscus aemula (Woron.) Schischk. A. sylvestris (L.) Hoffm. Anthricin, deoxypodophyllotoxin, isoanthricin, luteolin.50 Antitumor, glandular tumors, corns, warts. 

Synthesis of podophyllotoxin (3.86) in cell culture of Linum album results in yields comparable to those of the most efficient tissue cultures of Podophyllum hexandrum. In order to further improve L. album cultures, Seidel et al. (2002) investigated the biosynthesis of podophyllotoxin (3.86). They fed a number of labeled compounds that to L. album cell cultures to identify which of these compounds could be used as precursors to podophyllotoxin. They determined that the substitution pattern on the benzene ring is critical. The substitution has to be either 3-methoxy, 4-hydroxy, as in ferulic acid (3.33), or, alternatively, 3,4-methylenedioxycinnamic acid (3.90) can serve as precursor. The precursor of podophyllotoxin in L. album appears to be deoxypodophyllotoxin (3.83), based on the higher level of isotope incorporation in the latter compound. This means that 7-hydroxymatairesinol, the precursors of 5-methoxypodophyllotoxin in L. flavum (Xia et al., 2000), is not a precursor of podophyllotoxin in L. album. 

Podophyllotoxin-related cyclolignans include the important antitumour antimitotic podophyllotoxin ((MD)Phe(Phe) ] C40L) from Podophyllum species (Podophyllaceae) that inhibits topoisomerase and binds to tubulin. Podophyllotoxin-related compounds with antimitotic, cytotoxic and antitumour activity include 4 -demethylpodophyllotoxin, 4 -demethyldeoxypodophyllotoxin and deoxypodophyllotoxin. A variety of other kinds of cyclolignans and polycyclic neolignans have been characterized. 

Figure 4.11 Proposed biosynthetic steps involved in the biosynthesis of podophyllotoxin(-glucoside) and 6-methoxypodophyllotoxin(-glucoside). Steps catalyzed by yet unidentified enzymes are shown with dashed arrows. Enzymes involved are as follows (1) deoxypodophyllotoxin 7-hydroxylase, (2) deoxypodophyllotoxin...

Federolf, K., Alfermann, A.W. and Fuss, E. (2007) Aryltetralin-lignan formation in two different cell suspension cultures of Linum album Deoxypodophyllotoxin 6-hydroxylase, a key enzyme for the formation of 6-methoxypodophyllotoxin. Phytochemistry, 68,1397-A06. 

Molog, G.A., Empt, U., Kuhlmann, S., Van Uden, W., Eras, N., Alfermann, A.W. and Petersen, M. (2001) Deoxypodophyllotoxin 6-hydroxylase, a cytochrome P450 monooxygenase from cell cultures of Linum flavum involved in the biosynthesis of cytotoxic lignans. Planta, 214, 288-94. 

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