Resiniferatoxin

Source: Wikipedia, the free encyclopedia.
For other uses, see RTX.
Resiniferatoxin
Names
IUPAC name
[(1R,2R,6R,10S,11R,13R,15R,17R)-13-Benzyl-6-hydroxy-4,17-dimethyl-5-oxo-15-(prop-1-en-2-yl)-12,14,18-trioxapentacyclo[11.4.1.01,10.02,6.011,15]octadeca-3,8-dien-8-yl]methyl 2-(4-hydroxy-3-methoxyphenyl)acetate
Identifiers
3D model (
JSmol
)
ChEMBL
ChemSpider
IUPHAR/BPS
MeSH resiniferatoxin
UNII
  • InChI=1S/C37H40O9/c1-21(2)35-17-23(4)37-27(33(35)44-36(45-35,46-37)19-24-9-7-6-8-10-24)14-26(18-34(41)30(37)13-22(3)32(34)40)20-43-31(39)16-25-11-12-28(38)29(15-25)42-5/h6-15,23,27,30,33,38,41H,1,16-20H2,2-5H3/t23-,27+,30-,33-,34-,35-,36-,37-/m1/s1 ☒N
    Key: DSDNAKHZNJAGHN-MXTYGGKSSA-N checkY
  • C[C@@H]1C[C@]2([C@H]3[C@H]4[C@]1([C@@H]5C=C(C(=O)[C@]5(CC(=C4)COC(=O)Cc6ccc(c(c6)OC)O)O)C)O[C@](O3)(O2)Cc7ccccc7)C(=C)C
Properties
C37H40O9
Molar mass 628.718 g·mol−1
Density 1.35 ± 0.1 g/cm3
insoluble in water and hexane, soluble in ethyl acetate, ethanol, methanol, acetone, chloroform, and dichloromethane.
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 ?)
Resiniferatoxin
HeatAbove peak (highly toxic from pungency as defined by TRPV1 activation)
Scoville scale16,000,000,000 SHU

Resiniferatoxin (RTX) is a naturally occurring chemical found in resin spurge (

chili peppers.[2]

Biological activity

Resiniferatoxin has a score of 16 billion

analgesia, in part because the nerve endings die from calcium overload.[7][8]

Total synthesis

Figure 1. A partial synthesis of a resiniferatoxin derivative based on the method put forth by the Wender group of Stanford University. This partial synthesis shows how to create the three-ring backbone of RTX

A total synthesis of (+)-resiniferatoxin was completed by the Paul Wender group at Stanford University in 1997.[9] The process begins with a starting material of 1,4-pentadien-3-ol and consists of more than 25 significant steps. As of 2007, this represented the only complete total synthesis of any member of the daphnane family of molecules.[10]

One of the main challenges in synthesizing a molecule such as resiniferatoxin is forming the three-ring backbone of the structure. The Wender group was able to form the first ring of the structure by first synthesizing Structure 1 in Figure 1. By reducing the ketone of Structure 1 followed by oxidizing the furan nucleus with

allylic branch of the seven-membered ring in a trans conformation. Once this conformation is achieved, zirconocene-mediated cyclization of Structure 5 can occur, and oxidizing the resulting hydroxy group with TPAP will yield Structure 6. Structure 6 contains all three rings of the RTX backbone and can then be converted to resiniferatoxin through additional synthesis steps attaching the required functional groups.[9]

An alternative approach to synthesizing the three-ring backbone makes use of radical reactions to create the first and third rings in a single step, followed by the creation of the remaining ring. It has been proposed by the Masayuki Inoue group of the University of Tokyo.[11][12]

Toxicity

At 16 billion Scoville units, resiniferatoxin is rather toxic and can inflict

LD50 through oral ingestion is 148.1 mg/kg.[13]
It causes severe burning pain in sub-microgram (less than 1/1,000,000th of a gram) quantities when ingested orally.

Research

Sorrento Therapeutics has been developing RTX as a means to provide pain relief for forms of advanced cancer.[14][15]

The nerve desensitizing properties of RTX were once thought to be useful to treat

FDA approval for this use.[4] RTX has also previously been investigated as a treatment for interstitial cystitis, rhinitis, and lifelong premature ejaculation (PE).[15][16]

See also

References

  1. ^ Euphorbia poissonii in BoDD – Botanical Dermatology Database
  2. PMID 8709128
    .
  3. ^ National Institutes of Health, Clinical Center Department of Perioperative Medicine Chemical from cactus-like plant shows promise in controlling surgical pain, while leaving touch and coordination intact, rat study shows News release December 21, 2017, retrieved 28 February 2018.
  4. ^
    ISBN 978-1449631130
    .
  5. S2CID 24829016
    .
  6. PMID 2174484
    .
  7. S2CID 9429182
    .
  8. PMID 11124944
    .
  9. ^
    doi:10.1021/ja972279y
    .
  10. ^ Seiple, I.B. (March 17, 2007). "Daphnane, Tigliane, Ingenane and Lathyrane Diterpenes" (PDF). scripps.edu.
  11. ^ "Resiniferatoxin– A Radical Approach – Chemical Science Blog". blogs.rsc.org.
  12. doi:10.1039/C3SC50329A
    .
  13. ^ "Material Safety Data Sheet for resiniferatoxin, 2009" (PDF).
  14. PMID 27529257
    .
  15. ^ a b "Resiniferatoxin - Sorrento Therapeutics - AdisInsight". adisinsight.springer.com. 2019-01-24.
  16. S2CID 23297142
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Resiniferatoxin&oldid=1193635155"