Ptaquiloside

Ptaquiloside

Names
IUPAC name (2R,3aR,7S,7aR)-7-hydroxy-2,5,7-trimethyl-3a-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-spiro[3,7a-dihydro-2H-indene-6,1'-cyclopropane]-1-one
Identifiers
CAS Number	87625-62-5=
Beilstein Reference	3632862
ChemSpider	10312775
Jmol interactive 3D	Image
KEGG	C19515
InChI InChI=1S/C20H30O8/c1-9-6-20(28-17-15(25)14(24)13(23)11(8-21)27-17)7-10(2)19(4-5-19)18(3,26)16(20)12(9)22/h7,9,11,13-17,21,23-26H,4-6,8H2,1-3H3/t9-,11-,13-,14+,15-,16-,17+,18+,20-/m1/s1
SMILES C[C@@H]1C[C@]2(C=C(C3(CC3)[C@@]([C@H]2C1=O)(C)O)C)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O
Properties
Chemical formula	C20H30O8
Molar mass	398.45 g·mol^−1
Melting point	85 to 89 °C (185 to 192 °F; 358 to 362 K)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Ptaquiloside is the major toxin of bracken, and was first isolated in 1983.^[2] Its chemical stereostructure was determined to be norsesquiterpene glucoside of illudane type by Yamada and co-workers.^[3]

The carcinogenicity of ptaquiloside was proven in 1984,^[4][5] and ptaquiloside was shown to be responsible for the characteristic biological effects of bracken, such as acute bracken poisoning, bright blindness in sheep, mutagenicity, clastogenic effects and genotoxicity.^[6]

In a weakly alkaline solution, ptaquiloside is gradually converted, with concomitant elimination of glucose, into an unstable compound “dienone”, which is the activated form of ptaquiloside and acts as a powerful alkylating agent. The “dienone” alkylates the purine bases (adenine and guanine) of DNA, and then the alkylated purine parts are spontaneously removed from DNA: subsequently the cleavage of DNA occurs (DNA damage).^[6] Prakash and co-workers suggested ptaquiloside-induced carcinogenesis was initiated by the activation of the H-Ras oncogene.^[7]

From the chemical and ecological viewpoints, quantitative analyses of ptaquiloside in bracken were intensively performed worldwide. The ptaquiloside content of bracken proved to vary: for example, concentrations of ptaquiloside in the dried fronds of bracken were 0.1-0.6%.^[6]

In 2004, Danish scientist Lars Holm Rasmussen released a study showing the chemical can leach from the plant into the water supply, which may explain an increase in the incidence of gastric and oesophageal cancers in humans in bracken-rich areas.^[8] In addition, livestock have been known to eat the young shoots and fronds, which can then cause cancer in the animals, especially when untreated. Ptaquiloside has been identified in the milk of cows and groundwater. Humans can be exposed by direct consumption of the plant, contaminated water or milk, and spore inhalation.^[9]

It has been suggested that selenium supplementation can prevent as well as reverse the immunotoxic effects induced by ptaquiloside.^[10]

References

1. Kimiaki Saitoa, T. N.; Nagao, T.; Takatsuki, S.; Koyama, K.; Natori, S. (1990). "The sesquiterpenoid carcinogen of bracken fern, and some analogues, from the pteridaceae". Phytochemistry 29 (5): 1475–1479. doi:10.1016/0031-9422(90)80104-O.
2. Niwa, Haruki; Ojika, Makoto; Wakamatsu, Kazumasa; Yamada, Kiyoyuki; Hirono, Iwao; Matsushita, Kazuhiro (1983). "Ptaquiloside, a novel norsesquiterpene glucoside from bracken, Pteridium aquilinum var. latiusculum". Tetrahedron Letters 24 (38): 4117–4120. doi:10.1016/S0040-4039(00)88276-3.
3. Niwa, Haruki; Ojika, Makoto; Wakamatsu, Kazumasa; Yamada, Kiyoyuki; Ohba, Shigeru; Saito, Yoshihiko; Hirono, Iwao; Matsushita, Kazuhiro (1983). "Stereochemistry of ptaquiloside, a novel norsesquiterpene glucoside from bracken, Pteridium aquilinum var. latiusculum". Tetrahedron Letters 24 (48): 5371–5372. doi:10.1016/S0040-4039(00)87871-5.
4. Hirono, I.; Aiso, S.; Yamaji, T.; Mori, H.; Yamada, K.; Niwa, H.; Ojika, M.; Wakamatsu, K.; Kigoshi, H.; Niiyama, K; Uosaki, Y. (October 1984). "Carcinogenicity in rats of ptaquiloside isolated from bracken". Gann 75 (10): 833–836. PMID 6510632.
5. Hirono, I.; Ogino, H.; Fujimoto, M.; Yamada, K.; Yoshida, Y.; Ikagawa, M.; Okumura, M. (November 1987). "Induction of tumors in ACI rats given a diet containing ptaquiloside, a bracken carcinogen". Journal of the National Cancer Institute 79 (5): 1143–1149. PMID 3479640.
6. Yamada, Kiyoyuki; Ojika Makoto; Kigoshi, Hideo (August 2007). "Ptaquiloside, the major toxin of bracken, and related terpene glycosides: chemistry, biology and ecology". Natural Product Reports 24 (4): 798–813. doi:10.1039/b614160a. PMID 17653360.
7. Shahin, Mahmood; Moore, Michael R.; Worrall, Simon; Smith, Barry L.; Seawright, Alan A.; Prakash, Arungundrum S. (September 1998). "H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: comparison of acute and chronic toxicity in rats". Biochemical and Biophysical Research Communications 250 (2): 491–497. doi:10.1006/bbrc.1998.9341. PMID 9753659.
8. Ravilious, Kate (September 9, 2004). "The fatal fern". The Guardian. Retrieved April 15, 2012.
9. Gomes, Joana; Magalhães, Ana; Michel, Valérie; Amado, Inês F.; Aranha, Paulo; Ovesen, Rikke G.; Hansen, Hans C. B.; Gärtner, Fátima; Reis, Celso A.; Touati, Eliette (March 2012). "Pteridium aquilinum and its ptaquiloside toxin induce DNA damage response in gastric epithelial cells, a link with gastric carcinogenesis". Toxicological sciences 126 (1): 60–71. doi:10.1093/toxsci/kfr329. PMID 22143989.
10. Latorre, A.O.; Caniceiro, B.D.; Wysocki H.L., Jr; Haraguchi, M.; Gardner, D.R.; Górniak, S.L. (February 2011). "Selenium reverses Pteridium aquilinum-induced immunotoxic effects". Food and chemical toxicology 49 (2): 464–470. doi:10.1016/j.fct.2010.11.026. PMID 21112370. Cite uses deprecated parameter |coauthors= (help)