Total Synthesis of Palytoxin Armstrong, R.W., Beau, J. M: Cheon, S H; Christ, H;kaloka,H:Ham,WH.Hawkins,LD; Jir WJ McWhorter, w.w., Jr. Mizuno, M, Nakata, M Stutz, A.E., Talamas, F.X.: Taniguchi, M: Tino J.A., Ueda, K, Uenishi, J, White, J B, Yonaga OH M.JAm. Chem. Soc., 1989, 111, 7525: Armstrong, OH JM. Fujioka, H, Ham, W.H., Hawkins, L D; Jin, H Kang, S.H., Kishi, Y, Martinelli, MJ McWhorter, w.w., Jr, Mizuno, M: Nakata, M Me Stutz, A.E., Talamas, F.X.: Taniguchi, M, Ti HO\ J.A., Ueda, K. Uenishi, J: White, J B: Yo M. ibid, 1989, 111, 7530, Suh, E.M., Kishi, Y. ibid. OH 1994,116,11205; Kishi,Y.Chem,Scr.1987,27, OH 573, Kishi,Y. Pure Appl Chem, 1989, 61, 313 HO OH Me oh Me OH OH OH OH OH OH Y Kishi OH OH OH OH HO Chris Hupp Cem852
Total Synthesis of Palytoxin Total Synthesis of Palytoxin O NH2 OH O O OH OH O HO OH OH OH OH OH OH OH HO OH O Me OH OH OH O OH HO OH OH H O OH OH OH HO O O Me O N H N H HO OH OH Me OH H HO OH OH Me OH HO Me OH OH OH HO OH OH O O OH Me OH Me OH Armstrong, R.W.; Beau, J.M.; C heon, S.H.; C hrist, W.J.; F ujioka, H.; Ham, W.H.; Hawkins, L.D.; Jin, H.; Kan g, S.H.; Kishi, Y.; Martinelli, M.J.; McWhorter, W.W., Jr.; Mizuno, M.; Nakata, M.; Stutz, A.E.; Talamas, F.X.; Taniguchi, M.; Tino, J.A.; Ueda, K.; Uenishi, J.; W hite, J.B.; Yonaga, M. J.Am.Chem.Soc., 1989, 111, 7525; Armstrong, R.W.; Beau, J.M.; C heon, S.H.; C hrist, W.J.; F ujioka, H.; Ham, W.H.; Hawki ns, L.D.; Jin, H.; Kan g, S.H.; Kishi, Y.; Martinelli, M.J.; McWhorter, W.W., Jr.; Mizuno, M.; Nakata, M.; Stutz, A.E.; Talamas, F.X.; Taniguchi, M.; Tino, J.A.; Ueda, K.; Uenishi, J.; W hite, J.B.; Yonaga, M. ibid, 1989, 111, 7530; S u h, E.M.; Kishi, Y. ibid, 1994, 116, 11205; Kishi, Y. Chem,Scr. 1987, 27, 573; Kishi, Y. Pure & Appl. Chem, 1989, 61, 313. Y.Kishi Y.Kishi O NH2 OH O O OH OH O HO OH OH OH OH OH OH OH HO OH O Me OH OH OH O OH HO OH OH H O OH OH OH HO O Me O O N H N H HO OH OH Me OH H HO OH OH Me OH HO Me OH OH OH HO OH OH O O OH Me OH Me OH Chris Hupp CEM 852 Hupp CEM 852
What is Palytoxin? One of the most toxic non-peptidic natural products known to man vasoconstrictor Hemolysis agent Lethal dose for a human=<5ug
What is Palytoxin? What is Palytoxin? One of the most toxic non-peptidic natural products known to man! Vasoconstrictor Hemolysis agent Lethal dose for a human = <5µg
vasoconstriction and hemolysis Normal blood flow Restricted blood flow R,0 ENG WADAM. http://www.nlm.nih.gov/medlineplus/ency/imagepages/8983.htm http://www.physiology.rwth-aachen.de/user/martin/duunddeinblut/bl- Terminologie-d. html
Vasoconstriction and Hemolysis Vasoconstriction and Hemolysis http://www.nlm.nih.gov/medlineplus/ency/imagepages/8983.htm http://www.physiolog y.rwth-aachen.de/user/martin/Du U n dDeinBlut/BlTer minologie-d.html
What is Palytoxin? One of the most toxic non-peptidic natural products known to man! Vasoconstrictor a hemolysis agent Lethal dose for a human=<5ug Comes from the soft coral species palythoa Toxica found in a small tidal pool in maui http:/www.rockefeller.edu/pubinfo/012103ph
What is Palytoxin? What is Palytoxin? One of the most toxic non-peptidic natural products known to man! Vasoconstrictor Hemolysis agent Lethal dose for a human = <5µg http://www.rockefeller.ed u/pubinfo/012103.ph p Comes from the soft coral species Palythoa Toxica found in a small tidal pool in Maui
From the Tidal pool to the lab The gross structure was first reported by two groups Hirata--Japanl a Moore--Hawaii2 64 stereogenic centers a 115 carbon backbone One of the longest contiguous carbon chains in a natural product a There are about 27 different stereoisomers Y Kishi succeeded in elucidating the complete structure of palytoxin in 1982 and then completed the synthesis in 1994 Jremura, D. Ueda, K, Hirata, Y; Naoki, H, Iwashita, T. Tetrahedron Lett. 1981, 22, 2781 2Moore. R.E.: Bartolini. G. J J. Am. Chem. Soc. 1981. 103. 2491 Ishi et
From the Tidal Pool to the Lab From the Tidal Pool to the Lab The gross structure was first reported by two groups: The gross structure was first reported by two groups: Hirata —Japan 1 Moore —Hawaii 2 64 stereogenic centers stereogenic centers 115 carbon backbone carbon backbone ⇒ One of the One of the longest longest contiguous carbon chains in a natural product contiguous carbon chains in a natural product There are about There are about 271 different stereoisomers different stereoisomers Y. Kishi succeeded in elucidating the complete Y. Kishi succeeded in elucidating the complete structure of structure of palytoxin palytoxin in 1982 and then completed the in 1982 and then completed the synthesis in 1994 synthesis in 1994 3 1Ure mura, D.; Ueda, K.; Hirata, Y.; Naoki, H.; Iwashita, T. Tetrahedron Lett. 1981, 22, 2781 2Moore, R.E.; Bartolini, G. J. J. Am. Chem. Soc. 1981, 103, 2491 3Kishi et al