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Phorbol

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Phorbol[1]
Phorbol
Names
IUPAC name
1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5H-cyclopropa[3,4]benz[1,2-e]azulen-5-one
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.162.035 Edit this at Wikidata
  • InChI=1S/C20H28O6/c1-9-5-13-18(24,15(9)22)7-11(8-21)6-12-14-17(3,4)20(14,26)16(23)10(2)19(12,13)25/h5-6,10,12-14,16,21,23-26H,7-8H2,1-4H3/t10-,12+,13-,14-,16-,18-,19-,20-/m1/s1 ☒N
    Key: QGVLYPPODPLXMB-UBTYZVCOSA-N ☒N
  • InChI=1/C20H28O6/c1-9-5-13-18(24,15(9)22)7-11(8-21)6-12-14-17(3,4)20(14,26)16(23)10(2)19(12,13)25/h5-6,10,12-14,16,21,23-26H,7-8H2,1-4H3/t10-,12+,13-,14-,16-,18-,19-,20-/m1/s1
    Key: QGVLYPPODPLXMB-UBTYZVCOBR
  • OCC1=C[C@]([C@@](C(C)4C)([H])[C@]4(O)[C@H](O)[C@H]2C)([H])[C@]2(O)[C@@](C=C(C)C3=O)([H])[C@@]3(O)C1
Properties
C20H28O6
Molar mass 364.44 g/mol
Melting point 250 to 251 °C (482 to 484 °F; 523 to 524 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Phorbol is a natural, plant-derived organic compound. It is a member of the tigliane family of diterpenes. Phorbol was first isolated in 1934 as the hydrolysis product of croton oil, which is derived from the seeds of the purging croton, Croton tiglium.[2][3][4][5][6] The structure of phorbol was determined in 1967.[7][8] Phorbol is identified as the active constituent of the highly toxic New World tropical manchineel or 'beach apple' Hippomane mancinella.[9] It is very soluble in most polar organic solvents, as well as in water. In the manchineel, this leads to an additional exposure risk during rain, where liquid splashing from an undamaged tree may also be injurious.

Various esters of phorbol have important biological properties, the most notable of which is the capacity to act as tumor promoters through activation of protein kinase C.[10] They mimic diacylglycerols, glycerol derivatives in which two hydroxyl groups have reacted with fatty acids to form esters. The most common phorbol ester is 12-O-tetradecanoylphorbol-13-acetate (TPA), also called phorbol-12-myristate-13-acetate (PMA), which is used as a biomedical research tool in models of carcinogenesis. TPA, together with ionomycin, can also be used to stimulate T-cell activation, proliferation, and cytokine production, and is used in protocols for intracellular staining of these cytokines.[11]

Total synthesis

The total synthesis of phorbol has been reported. [12] [13] [14]

References

  1. ^ Merck Index, 11th Edition, 7306
  2. ^ Flaschenträger B, v. Wolffersdorff R (1934). "Über den Giftstoff des Crotonöles. 1. Die Säuren des Crotonöles". Helvetica Chimica Acta. 17 (1): 1444–1452. doi:10.1002/hlca.193401701179.
  3. ^ Flaschenträger B, Wigner G (1942). "Über den Giftstoff des Crotonöles. V. Die Gewinnung von Crotonharz, Dünnem Öl und Phorbol aus dem Crotonöl durch Alkoholyse". Helvetica Chimica Acta. 25 (3): 569–581. doi:10.1002/hlca.19420250315.
  4. ^ Kauffmann T, Neumann H, Lenhardt K (1959). "Zur Konstitution des Phorbols, I. Über die reduzierende Gruppe des Phorbols". Chemische Berichte. 92 (8): 1715–1726. doi:10.1002/cber.19590920802.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Kauffmann T, Eisinger A, Jasching W, Lenhardt K (1959). "Zur Konstitution des Phorbols, I. Über die reduzierende Gruppe des Phorbols". Chemische Berichte. 92 (8): 1727–1738. doi:10.1002/cber.19590920803.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Tseng S-S, van Duuren BL, Solomon JJ (1977). "Synthesis of 4aα-Phorbol 9-Myristate 9a-Acetate and Related Esters". J. Org. Chem. 42 (33): 3645–3649. doi:10.1021/jo00443a002.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Hecker E, Bartsch H, Bresch H, Gschwendt M, Härle B, Kreibich G, Kubinyi H, Schairer HU, v. Szczepanski C, Thielmann HW (1967). "Structure and Stereochemistry of the Tetracyclic Diterpene Phorbol from Croton tiglium L". Tetrahedron Letters. 8 (33): 3165–3170. doi:10.1016/S0040-4039(01)89890-7.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Pettersen RC, Ferguson G, Crombie L, Games ML, Pointer DJ (1967). "The Structure and Stereochemistry of Phorbol, Diterpene Parent of Co-carcinogens of Croton Oil". Chem. Commun. (London). 1967 (14): 716–717. doi:10.1039/C19670000716.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Adolf, W; Hecker, E (1984). "On the active principles of the spurge family. X. Skin irritants, cocarcingoens, and cryptic carcinogens from the latex of the manchineel tree". J Nat Prod. (47): 482–496. PMID 6481361.
  10. ^ Blumberg PM (1988). "Protein Kinase C as the Receptor for the Phorbol Ester Tumor Promoters: Sixth Rhoads Memorial Award Lecture" (pdf). Cancer Res. 48 (1): 1–8. PMID 3275491.
  11. ^ "Flow Cytometry Intracellular Staining Guide". eBioscience, Inc. Retrieved 2011-09-25.
  12. ^ Studies on tumor promoters. 8. The synthesis of phorbol Paul A. Wender, Hiroshi Kogen, Hee Yoon Lee, John D. Munger Jr., Robert S. Wilhelm, and Peter D. Williams Journal of the American Chemical Society 1989 111 (24), 8957-8958 doi:10.1021/ja00206a050
  13. ^ The First Formal Asymmetric Synthesis of Phorbol Paul A. Wender,*, Kenneth D. Rice, and, and Mark E. Schnute Journal of the American Chemical Society 1997 119 (33), 7897-7898 doi:10.1021/ja9706256
  14. ^ Nineteen-step total synthesis of (+)-phorbol Shuhei Kawamura,Hang Chu, Jakob Felding & Phil S. Baran Nature (2016) doi:10.1038/nature17153
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