Palytoxin

Structural formula
General
Surname	Palytoxin
Molecular formula	C 129 H 223 N 3 O 54
Brief description	hygroscopic solid
External identifiers / databases
CAS number 11077-03-5 77734-92-0 (C 52-55 hemiacetal) 77734-91-9 (C 51-55 hemiacetal) EC number 634-569-7 ECHA InfoCard 100.162.538 PubChem 11105289 ChemSpider 9280425 Wikidata Q425134
properties
Molar mass	2680.13 g mol −1
Physical state	firmly
Melting point	> 300 ° C
solubility	soluble in water, pyridine and DMSO insoluble in acetone and chloroform
safety instructions
GHS labeling of hazardous substances danger H and P phrases H: 300-310-330 P: ?
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Palytoxin is a toxin from the dinoflagellate Ostreopis siamensis , some zoanthids of the genus Palythoa and cyanobacteria of the genus Trichodesmium , which is also extracted from plankton by some animals such as the soft coral Palythoa toxica or crust anemones and used to protect against predators. Until the discovery and structural elucidation of maitotoxin Palytoxin was the non-polymeric largest and not from amino acids built up natural products with the longest continuous carbon chain (115 chain links).

history

Palytoxin has long been used as a poison for spears by the indigenous people of Hawaii . Its complex structure and absolute configuration could be clarified in the years 1981–1982. A first total synthesis of palytoxin was reported in 1994 by a group headed by Yoshito Kishi . To this day, the synthesis of this natural product with its 64 stereogenic centers is considered to be one of the greatest achievements in chemical synthesis.

toxicity

With an LD ₅₀ ( house mouse , intravenous ) of less than 150  ng per kg body weight, palytoxin is one of the most toxic organic substances; only maitotoxin and a number of proteins have a higher acute toxicity. The poison effect is due to a serious interference in active cellular transport systems for ions from the group of ATPases . Palytoxin changes the configuration of the Na-K-ATPase ( K _d = 20 pM ) in such a way that the directional specificity of the pumping action (for three Na ⁺ ions pumped out of the cell, two K ⁺ ions are transported into the cell with hydrolysis of one molecule of ATP ) and the ion pump becomes an ion channel . This leads to a decrease in the concentration gradient between the extra- and intracellular space, thus of the osmotic pressure , the membrane potentials ( depolarization ) etc. with the corresponding effects on the cells or the organism. The symptoms of poisoning can be deduced from the mode of action: hemolysis , rhabdomyolysis , severe muscle spasms , bronchospasm , arterial hypertension , pathologically changed ECG . The symptoms of poisoning set in very quickly and can lead to rapid death within a few minutes.

Accidents

In 2018 there was an accident in Steventon , United Kingdom , in which a family ingested palytoxin in the air after cleaning an aquarium.

Individual evidence

1. ↑ ^{a b c d} Entry on palytoxin. In: Römpp Online . Georg Thieme Verlag, accessed on December 29, 2014.
2. ↑ There is not yet a harmonized classification for this substance . A labeling of Palytoxin from palythos caribaerum in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on May 28, 2019, is shown, which is derived from a self-classification by the distributor .
3. ↑ ^{a b c d e} J. Patocka, RC Gupta, QH Wu, K. Kuca: Toxic potential of palytoxin. In: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. Volume 35, Number 5, October 2015, pp. 773-780, doi : 10.1007 / s11596-015-1506-3 , PMID 26489638 .
4. ↑ P. Ciminiello, C. Dell'Aversano, E. Dello Iacovo, M. Forino, L. Tartaglione, M. Pelin, S. Sosa, A. Tubaro, O. Chaloin, M. Poli, G. Bignami: Stereoisomers of 42-hydroxy palytoxin from Hawaiian Palythoa toxica and P. tuberculosa: stereostructure elucidation, detection, and biological activities. In: Journal of Natural Products. Volume 77, Number 2, February 2014, pp. 351-357, doi : 10.1021 / np4009514 , PMID 24512352 .
5. ^ RE Moore, G. Bartolini: Structure of palytoxin. In: J. Am. Chem. Soc. 103: 2491 (1981).
6. ↑ D. Uemura, K. Ueda, Y. Hirata: Further studies on palytoxin. II. Structure of palytoxin. In: Tetrahedron Letters 22, 2781 (1981).
7. ^ RE Moore, G. Bartolini, J. Barchi, AA Bothner-By, J. Dadok, J. Ford: Absolute stereochemistry of palytoxin. In: J. Am. Chem. Soc. 104: 3776 (1982).
8. ↑ RW Armstrong, JM Beau et al .: Total synthesis of palytoxin carboxylic acid and palytoxin amide. In: J. Am. Chem. Soc. 111: 7530 (1989).
9. ↑ Y. Kishi: Natural products synthesis: palytoxin In: Pure Appl. Chem. 61, 313 (1989).
10. ↑ EM Suh, Y. Kishi: Synthesis of Palytoxin from Palytoxin Carboxylic Acid. In: J. Am. Chem. Soc. 116: 11205 (1994).
11. ↑ Tomáš Hudlický, Josephine W. Reed: The way of synthesis: evolution of design and methods for natural products. Wiley, 2007, ISBN 978-3-527-32077-6 . Pp. 891-905.
12. ^ Cleaning this fish tank almost killed an entire family . In: The Independent . April 6, 2018 ( independent.co.uk [accessed April 10, 2018]).