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Resiniferatoxin

Resiniferatoxin is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Resiniferatoxin rather than just read about it. In short: Resiniferatoxin (RTX) is a naturally occurring chemical found in resin spurge (Euphorbia resinifera), a cactus-like plant commonly found in Morocco, and in Euphorbia poissonii found in northern Nigeria. It is a potent functional analog of capsaicin, the active ingredient in chili peppers.

Resiniferatoxin — main illustration
Resiniferatoxin — illustration

Key takeaways

  • Resiniferatoxin belongs to chemistry; place it in that map before memorising details.
  • Learn the definition first, then one example that makes the definition concrete.
  • Connect Resiniferatoxin to a quantity you can measure, compute or draw — that is where exam questions come from.
  • Reproduce the core statement of Resiniferatoxin from memory before moving on to harder problems.

Reference excerpt

Resiniferatoxin (RTX) is a naturally occurring chemical found in resin spurge (Euphorbia resinifera), a cactus-like plant commonly found in Morocco, and in Euphorbia poissonii found in northern Nigeria. It is a potent functional analog of capsaicin, the active ingredient in chili peppers.

Biological activity Resiniferatoxin has a score of 16 billion Scoville heat units, making pure resiniferatoxin about 500 to 1000 times hotter than pure capsaicin. Resiniferatoxin activates transient vanilloid receptor 1 (TRPV1) in a subpopulation of primary afferent sensory neurons involved in nociception, the transmission of physiological pain. TRPV1 is an ion channel in the plasma membrane of sensory neurons and stimulation by resiniferatoxin causes this ion channel to become permeable to cations, especially calcium. The influx of cations causes the neuron to depolarize, transmitting signals similar to those that would be transmitted if the innervated tissue were being burned or damaged. This stimulation is followed by desensitization and analgesia, in part because the nerve endings die from calcium overload.

Total synthesis A total synthesis of (+)-resiniferatoxin was completed by the Paul Wender group at Stanford University in 1997. 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. 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 m-CPBA and converting the resulting hydroxy group to an oxyacetate, Structure 2 can be obtained. Structure 2 contains the first ring of the three-ring structure of RTX. It reacts through an oxidopyrylium cycloaddition when heated with DBU in acetonitrile to form Structure 4 by way of Intermediate 3. Several steps of synthesis are required to form Structure 5 from Structure 4, with the main goal of positioning the 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. 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.

Toxicity At 16 billion Scoville units, resiniferatoxin is toxic and can inflict chemical burns in minute quantities. The primary action of resiniferatoxin is to activate sensory neurons responsible for the perception of pain. It is currently the most potent TRPV1 agonist known, with a binding affinity for TRPV1 about 500 times higher than pure capsaicin, the active ingredient in hot chili peppers such as those produced by Capsicum annuum. It is 1000-10,000 times more potent than capsaicin for effects on thermoregulation and neurogenic inflammation. For rats, LD50 through oral ingestion is 148.1 mg/kg. It causes severe burning pain in sub-microgram (less than 1/1,000,000th of a gram) quantities when ingested orally.

Research The nerve desensitizing properties of RTX are thought to be useful to treat overactive bladder (OAB) by preventing the bladder from transmitting "sensations of urgency" to the brain, similar to how they can prevent nerves from transmitting signals of pain; RTX has never received Federal Drug Administration approval for this use. RTX has also previously been investigated as a treatment for interstitial cystitis, rhinitis, and lifelong premature ejaculation (PE).

See also Discovery and development of TRPV1 antagonists Iodoresiniferatoxin List of investigational analgesics Phenylacetylrinvanil Transient receptor potential Tinyatoxin

References

External links "Fiery Pepper May Hold Key to Easing Pain". Lauran Neergaard, Associated Press, 16 January 16, 2006. CID Resiniferatoxin from PubChem

Illustrations

Resiniferatoxin illustration
Resiniferatoxin: 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
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

Worked examples

Example 1 — a first encounter with Resiniferatoxin

Start with the simplest possible case. Write down what Resiniferatoxin claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Resiniferatoxin before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Resiniferatoxin ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Resiniferatoxin

In research
Resiniferatoxin appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry
Engineering practice reuses Resiniferatoxin in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom
Resiniferatoxin is common in secondary-school and first-year university syllabi. It links to neighbouring topics Analgesics, Benzyl compounds, Carboxylate esters, so understanding it makes those chapters shorter.
In everyday life
Look for Resiniferatoxin outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.
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How to study Resiniferatoxin in 20 minutes

  1. Read the reference excerpt below once, without taking notes.
  2. Close the page and write down what Resiniferatoxin means in your own words.
  3. Compare your version with the excerpt and mark what you missed.
  4. Work through the three examples above with pen and paper.
  5. Explain Resiniferatoxin out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Resiniferatoxin in simple terms?

Resiniferatoxin (RTX) is a naturally occurring chemical found in resin spurge (Euphorbia resinifera), a cactus-like plant commonly found in Morocco, and in Euphorbia poissonii found in northern Nigeria. It is a potent functional analog of capsaicin, the active ingredient in chili peppers.

Why does Resiniferatoxin matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Resiniferatoxin?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Resiniferatoxin.

Tags

  • Analgesics
  • Benzyl compounds
  • Carboxylate esters
  • Cyclopentenes
  • Heterocyclic compounds with 5 rings
  • Neurotoxins
  • Ortho esters
  • Plant toxins
  • Terpenes and terpenoids
  • Transient receptor potential channel modulators

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