4368-28-9 Usage
Description
Tetrodotoxin (TTX) is a highly potent, nonprotein, heat-stable toxin that acts as a selective sodium channel blocker. It is found in the liver and sex organs of certain marine animals, such as pufferfish, porcupine fish, ocean sunfish, and toadfish, as well as some amphibians, octopuses, and shellfish species. TTX is produced by certain bacteria, such as Pseudomonas and Vibrio, and can be toxic to humans, interfering with nerve-to-muscle signal transmission and causing paralysis. Its mechanism of action involves binding to voltage-gated sodium channels in nerve cell membranes, blocking the passage of sodium ions into the nerve cell, and inhibiting the firing of action potentials in nerves.
Uses
Used in Pharmaceutical and Biomedical Research:
Tetrodotoxin is used as a chemical tool in physiological and pharmacological laboratories for its channel-blocking action. It has been investigated for potential therapeutic uses, including suppressing pain in cancer patients, preventing ischemic brain damage following a stroke, relieving withdrawal symptoms in opiate addicts, and serving as an anesthetic agent.
Used in Neurological Applications:
TTX is employed as a highly selective, reversible sodium channel blocker, making it valuable in studying the function and behavior of voltage-gated sodium channels in the nervous system. This application aids in understanding various neurological disorders and developing targeted treatments.
Used in Marine Biology and Ecology:
Tetrodotoxin is used as a biomarker for the presence of specific marine species and bacteria that produce or accumulate the toxin. This information is crucial for understanding the distribution, ecology, and potential risks associated with TTX-containing organisms in the marine environment.
Used in Drug Development:
TTX is utilized in the development of drugs targeting voltage-gated sodium channels, which are implicated in various diseases, including chronic and breakthrough pain in advanced cancer patients. By studying the interactions between TTX and these channels, researchers can develop more effective and safer medications for pain management and other conditions.
References
https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750019.html
https://en.wikipedia.org/wiki/Tetrodotoxin
Biological Activity
Selective inhibitor of Na + channel conductance. Binding is reversible and of high affinity (K d = 1-10 nM). Blocks in a use-dependent manner.
Safety Profile
Poison by ingestion,
intraperitoneal, subcutaneous, and
intravenous routes. When heated to
decomposition it emits toxic fumes of Nox.
Toxicity evaluation
TTX is a selective sodium channel blocker that can block nerve
and muscle conductions; action potentials are blocked while
resting membrane potentials and resting membrane resistance
are not affected. TTX blocks axonal transmission by lowering
the conductance of sodium at nodes of Ranvier. Vomiting
occurs because the toxin can act directly at or near the
chemoreceptor trigger zone. Respiratory depression is caused
by either a specific action of tetrodotoxin on the brain’s respiratory
center or because paralysis of respiratory nerves and
muscles occurs.
Check Digit Verification of cas no
The CAS Registry Mumber 4368-28-9 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 4,3,6 and 8 respectively; the second part has 2 digits, 2 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 4368-28:
(6*4)+(5*3)+(4*6)+(3*8)+(2*2)+(1*8)=99
99 % 10 = 9
So 4368-28-9 is a valid CAS Registry Number.
InChI:InChI=1/C11H17N3O8/c12-8-13-6(17)2-4-9(19,1-15)5-3(16)10(2,14-8)7(18)11(20,21-4)22-5/h2-7,15-20H,1H2,(H3,12,13,14)/t2-,3-,4-,5+,6-,7+,9+,10-,11+/m1/s1
4368-28-9Relevant articles and documents
Total Synthesis of (?)-Tetrodotoxin and 11-norTTX-6(R)-ol
Maehara, Tomoaki,Motoyama, Keisuke,Toma, Tatsuya,Yokoshima, Satoshi,Fukuyama, Tohru
supporting information, p. 1549 - 1552 (2017/02/05)
The enantioselective total synthesis of (?)-tetrodotoxin [(?)-TTX] and 4,9-anhydrotetrodotoxin, which are selective blockers of voltage-gated sodium channels, was accomplished from the commercially available p-benzoquinone. This synthesis was based on efficient stereocontrol of the six contiguous stereogenic centers on the core cyclohexane ring through Ogasawara's method, [3,3]-sigmatropic rearrangement of an allylic cyanate, and intramolecular 1,3-dipolar cycloaddition of a nitrile oxide. Our synthetic route was applied to the synthesis of the tetrodotoxin congeners 11-norTTX-6(R)-ol and 4,9-anhydro-11-norTTX-6(R)-ol through late-stage modification of the common intermediate. Neutral deprotection at the final step enabled easy purification of tetrodotoxin and 11-norTTX-6(R)-ol without competing dehydration to their 4,9-anhydro forms.
First asymmetric total synthesis of tetrodotoxin
Ohyabu, Norio,Nishikawa, Toshio,Isobe, Minoru
, p. 8798 - 8805 (2007/10/03)
Tetrodotoxin, a toxic principle of puffer fish poisoning, is one of the most famous marine natural products because of the complex structure having many functional groups and its potent biological activity leading to death. Since the structure elucidation in 1964, this toxin has been recognized as a formidable target molecule for total synthesis. We have recently achieved the first asymmetric total synthesis from 2-acetoxy-tri-O-acetyl-D-glucal as a chiral starting material. The highly hydroxylated cyclohexane ring was constructed by Claisen rearrangement and regioselective hydroxylations of an acetone moiety and an intramolecular directed aldol condensation of the precursor having methyl ketone with dihydroxyacetone, which was synthesized through Sonogashira coupling. Installation of nitrogen functionality was unsuccessful through an attempted Overman rearrangement. We, therefore, employed a new intramolecular conjugate addition strategy between the carbamate and unsaturated ester groups. The α-hydroxyl lactone moiety was synthesized through an intramolecular epoxide opening by the Z-enolate of aldehyde, which was followed by oxidation - reduction of the resulting cyclic vinyl ether. The lactone was then converted to a protected ortho ester, and then gunanidinylation was followed by cleavage of the 1,2-glycol to give the fully protected tetrodotoxin. Selection of the protective groups has finally led us to accomplish the total synthesis of tetrodotoxin in an enantiomerically pure form. All the stereogenic centers were controlled with high selectivity, and the hydroxyl groups were differently protected to discriminate for the future analogue synthesis of a bioorganic program. The synthetic tetrodotoxin was purifed by ion exchange chromatography and characterized to be identifical with the natural compound.
