Podophyllum hexandrum

The plant. Podophyllum hexandrum (Podophyllaceae Berberidaceae), produces podophyllotoxin (3) and its glycoside, both of which are effective anticancer agents. Commercial production of podophyllotoxin from... 

Figure 3-11. Biosynthesis of podophyllotoxinin in Podophyllum hexandrum, according to Broomhead et al. (1991). The dotted arrow refers to a series of reactions that have not yet been fully elucidated formation of a methylene dioxybridge, and hydroxylation and methylation reactions.

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. 

Callitris drummondii, Juniperus sabina, J. virginiana, Diphylleia grayi, D. sinensis, Podophyllum hexandrum, E peltatum, P. pleianthum (Podophyllaceae) [rhizome] Podophyllum hexandrum,... 

R peltatum, R pleianthum (Podophyllaceae) [rhizome] Podophyllum hexandrum,... 

Coniferin (the (3-D-glucoside of coniferyl alcohol) is accumulated prior to lignin formation as well as in lignan-s)mthesizing cell cultures (e.g. Berlin et al, 1986 Van Uden et al., 1991 Smollny et al, 1998). Coniferin and lignan contents were found to be inversely correlated in cell cultures. However, there is no direct proof for a transformation of stored coniferin to lignans. Feeding of coniferin resulted in an enhanced podophyllotoxin accumulation in cell cultures of Podophyllum hexandrum (Van Uden et al, 1990). 

Heyenga, A.G., Lucas, J.A. and Dewick, P.M. (1990) Production of tumour-inhibitory lignans in callus cultures of Podophyllum hexandrum. Plant Cell Rep., 9, 382-5. 

Jackson, D.E. and Dewick, P.M. (1984) Biosynthesis of Podophyllum lignans. II. Interconversions of aryltetralin lignans in Podophyllum hexandrum. Phytochemistry, 23, 1037-12. 

Van Uden, W., Pras, N. and Malingre, T.M. (1990) On the improvement of the podophyllotoxin production by phenylpropanoid precursor feeding to cell cultures of Podophyllum hexandrum Royle. Plant Cell Tiss. Org. Cult., 23, 217-24. 

Sharma, K.D., Singh, B.M., Sharma, T.N., Katoch, M. and Guleria, S. (2000). Molecular analysis of variability in Podophyllum hexandrum Royle- an endangered medicinal herb of north western Himalaya. Plant Gen. Res. Newsletter, 124 57-61. 

Podophyllum hexandrum Royle. Podophyllaceae Bankakri Fruit and Seed Used in wounds/cuts, tuberculosis and constipation... 

The broad-band decoupled and DEPT spectra of podophyllotoxin, C22H22OS, isolated from Podophyllum hexandrum, are shown. Although the molecule contains 22 carbons, only 18 signals are visible in the broad-band C-NMR spectrum. This would obviously mean that some of these signals represent more than one carbon. Pairs of C-lO/C-14, C-ll/C-13, and ll-OCHs/lS-OCHj are magnetically equivalent while C-6 and C-7 could show accidental overlap. With this information, assign chemical shifts to various carbon atoms in the molecule. 

Fraser, F.C. 1981. Letter to the editor. Mod. Med. Can. 36 1508. Gupta, M.L., P.K. Agrawala, P. Kumar, et al. 2008a. Modulation of gamma radiation-inflicted damage in Swiss albino mice by an alcoholic fraction of Podophyllum hexandrum rhizome. J. Med. Food ll(3) 486-492. 

Gupta, M.L., S. Sankhwar, S. Verma, et al. 2008b. Whole body protection to lethally irradiated mice by oral administration of semipurified fraction of Podophyllum hexandrum and post irradiation treatment of Picrorhiza kurroa. Tokai. Exp. Clin. Med. 33(1) 6-12. 

Lata, M., J. Prasad, S. Singh, et al. 2009. Whole body protection against lethal ionizing radiation in mice by REC-2001 A semi-purified fraction of Podophyllum hexandrum. Phytomedicine 16(l) 47-55. 

Sajikumar, S., and H.C. Goel. 2003. Podophyllum hexandrum prevents radiation-induced neuronal damage in postnatal rats exposed in utero. Phytother. Res. 17(7) 761-766. 

Podophyllum peltatum root Podophyllum hexandrum root Ruta graveolens herb Tanacetum vulgare herb Thuja occidentalis leaves... 

Iris versicolor rhizome and root Iris virginica rhizome and root Lobelia inflata herb Lobelia siphilitica herb Melia azedarach fruit, root bark Podophyllum peltatum root Podophyllum hexandrum root Sanguinaria canadensis root... 

Jackson, D. E. and P. M. Dewick, Cinnamic acid precursors of podophyllotoxin in Podophyllum hexandrum, Phytochemistry, 23. 1029-1035 (1984). 

Very recently Dewick has begun a thorough investigation of podophyllotoxin biosynthesis in Podophyllum hexandrum. Cinnamic and ferulic acids are each incorporated equally into both halves of the molecule, the carbon of the 0-methyl group of ferulic acid being retained by both ring A and ring C (Scheme 4). ... 

Ranuncul Ranuncul Berberid Podophyllum hexandrum BerPodhex... 

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