57444-62-9 Usage
Description
Resiniferatoxin (57444-62-9) is an ultrapotent TRPV1 activator with a Ki value of 43 pM. It is 100-10,000 times more potent than capsaicin for most responses and exhibits a distinct spectrum of activity compared to capsaicin. Resiniferatoxin is also a potent sensory neuron excitotoxin and has been shown to induce long-lasting analgesia in a rodent model of burn pain. It is a white to off-white solid and should be handled with care due to its severe irritant properties.
Uses
Used in Pharmaceutical Research:
Resiniferatoxin is used as an agonist to transient receptor potential vanilloid 2 (TRPV2) for complex preparation. This application is crucial for cryo-electron microscopy structural studies, which help in understanding the molecular mechanisms of TRPV2 and its role in various physiological processes.
Used in Immunological Studies:
Resiniferatoxin is employed to test its effect on immune responses to Pseudomonas aeruginosa in sensory neurons associated with the cornea. This application aids in understanding the role of TRPV2 in immune responses and its potential as a therapeutic target for treating infections caused by P. aeruginosa.
Used in Neurological Research:
Resiniferatoxin is used to study its effects in the denervation of peripheral sensory nerves in psoriatic mice. This application helps in understanding the role of TRPV1 activation in the pathophysiology of psoriasis and the potential of resiniferatoxin as a therapeutic agent for this condition.
Hazard
A poison.
Biological Activity
Ultrapotent analog of capsaicin that is an agonist at vanilloid receptors (K i = 43 pM). Like capsaicin, it acts as a selective modulator of primary afferent neurons. Also available as part of the Vanilloid TRPV1 Receptor Tocriset? .
Biochem/physiol Actions
Resiniferatoxin (RTX) is an analog of capsaicin. It effectively ablates corneal sensory neurons by activating transient receptor potential vanilloid 1 (TRPV1) channels. RTX facilitates corneal bacterial clearance. It also elicits protective functionality towards cardiac function in a rat model with congestive heart failure (CHF).
References
1) Szolcsanyi et al. (1990), Resiniferatoxin: an ultrapotent selective modulator of capsaicin-sensitive primary afferent neurons; J. Pharmacol. Exp. Ther., 255 923
2) Szallasi and Blumberg (1998), Resiniferatoxin and its analogs provide novel insights into the pharmacology of the vanilloid (capsaicin) receptor; Life Sci. 47 1399
3) Winter et al. (1990) Cellular mechanism of action of resiniferatoxin: a potent sensory neuron excitotoxin; Brain Res. 520 131
4) Salas et al. (2017) Local Resiniferatoxin Induces Long-Lasting Analgesia in a Rat Model of Full Thickness Thermal Injury; Pain Med. 18 2453
Check Digit Verification of cas no
The CAS Registry Mumber 57444-62-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,7,4,4 and 4 respectively; the second part has 2 digits, 6 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 57444-62:
(7*5)+(6*7)+(5*4)+(4*4)+(3*4)+(2*6)+(1*2)=139
139 % 10 = 9
So 57444-62-9 is a valid CAS Registry Number.
InChI:InChI=1/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
57444-62-9Relevant articles and documents
Total Synthesis of Resiniferatoxin Enabled by Radical-Mediated Three-Component Coupling and 7-endo Cyclization
Hashimoto, Satoshi,Katoh, Shun-Ichiro,Kato, Takehiro,Urabe, Daisuke,Inoue, Masayuki
, p. 16420 - 16429 (2017/11/22)
Resiniferatoxin (1) belongs to a daphnane diterpenoid family and has strong agonistic effects on TRPV1, a transducer of noxious temperature and chemical stimuli. The densely oxygenated trans-fused 5/7/6-tricarbocycle (ABC-ring) of 1 presents a daunting challenge for chemical synthesis. Here we report the development of a novel radical-based strategy for assembling 1 from three components: A-ring 9, allyl stannane 18b, and C-ring 17b. The 6-membered 17b, prepared from d-ribose derivative 19, was designed to possess the caged orthoester structure with α-alkoxy selenide as a radical precursor. Upon treatment of 17b with 18b, 9, and V-40, the potently reactive α-alkoxy bridgehead radical was generated from 17b and then sequentially coupled with 9 and 18b to yield 16b. This first radical reaction formed the hindered C9,10-linkage between the A and C-rings and extended the C4-chain on the A-ring in a stereoselective fashion. After derivatization of 16b into 15, the remaining 7-membered B-ring was cyclized in the presence of n-Bu3SnH and V-40 by utilizing the xanthate on the C-ring as the radical precursor and the allylic dithiocarbonate as the terminator. The second radical reaction thus enabled not only the 7-endo cyclization but also construction of the C8-stereocenter and the C6-exo olefin. Tricycle 14 was elaborated into the targeted 1 by a series of highly optimized chemoselective reactions. The present total synthesis of 1 demonstrates the advantages of radical reactions for linking hindered bonds within carbocycles without damaging preexisting functionalities, thereby offering a new strategic design for multistep target-oriented synthesis.
