3-Amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.17,11.01,6]tetradec-3-ene-5,9,12,13,14-pentol

Base Information

• Chemical Name: 3-Amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.17,11.01,6]tetradec-3-ene-5,9,12,13,14-pentol
• CAS No.: 4368-28-9
• Molecular Formula: C11H17N3O8
• Molecular Weight: 319.271
• Hs Code.: 30029090
• European Community (EC) Number: 224-458-8
• NCI Thesaurus Code: C78845
• Nikkaji Number: J32.331D
• Wikidata: Q104956801
• Wikipedia: Tetrodotoxin
• Mol file: 4368-28-9.mol

Synonyms:Fugu Toxin;Tarichatoxin;Tetradotoxin;Tetrodotoxin;Toxin, Fugu

Chemical Property of 3-Amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.17,11.01,6]tetradec-3-ene-5,9,12,13,14-pentol

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 1.58E-27mmHg at 25°C
• Melting Point: 225oC dec
• Refractive Index: 2.087
• Boiling Point: 702.6 °C at 760 mmHg
• PKA: 8.76 (water); 9.4 (50% alc)
• Flash Point: 378.7 °C
• PSA: 192.32000
• Density: 2.78 g/cm³
• LogP: -6.03400
• Storage Temp.: 2-8°C
• Solubility.: H2O: stable at pH 4-5 if stored frozensoluble
• XLogP3: -5.9
• Hydrogen Bond Donor Count: 8
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 1
• Exact Mass: 319.10156451
• Heavy Atom Count: 22
• Complexity: 562

Purity/Quality:

≥98% ^*data from raw suppliers

Tetrodotoxin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T+
• Hazard Codes: T+
• Statements: 26/27/28
• Safety Statements: 22-36/37/39-45-36/37-28

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Chemical Classes: Biological Agents -> Seafood Toxins
• Canonical SMILES: C(C1(C2C3C(N=C(NC34C(C1OC(C4O)(O2)O)O)N)O)O)O
• Recent ClinicalTrials: A Randomized, Double-Blind, Placebo Controlled, Multicenter, Efficacy and Safety Trial of Single Cycle Tetrodotoxin in the Treatment of Chemotherapy Induced Neuropathic Pain
• Description: Tetraodotoxin is a kind of extremely potent toxin which exists in the liver and sex organs of some fishes including pufferfish, porcupine fish, ocean sunfish, and toadfish as well as some kind of amphibian, octopus and shellfish species. It is also produced by some bacteria such as Pseudomonas and Vibrio. Tetraodotoxin is extremely toxic to human, interfering with the transmission of signals of nerves to muscles and further causing paralysis of the body muscle. It can be fatal in some cases. Its mechanism of action is inhibiting the firing of action potentials in nerves through binding to the voltage-gated sodium channels in nerve cell membrane and blocking the passages of sodium ions into the nerve cell. People should wear proper protective equipment upon operations and should be subject to proper treatment upon suffering from it. However, it has been under investigation on the treatment of chronic and breakthrough pain in advanced cancer patients. Tetrodotoxin (TTX) is a selective sodium channel blocker nonprotein heat-stable toxin. The mechanism of toxicity is through the blockage of fast voltage-gated sodium channels. The consumption of toxic amounts of TTX results primarily in neurologic and gastrointestinal signs and symptoms. TTX is widely distributed in marine taxa such as pufferfish and porcupine fish (suborders of the Tetraodontiformes order), salamanders of the family Salamandridae, Central American frogs (genus Atelopus), shellfish, starfish, crabs, and some species of ribbonworm and octopus. However, in terrestrial taxa, it is limited to a single class of vertebrates (Amphibia). TTX is now known to be produced not by puffer but by bacteria, and reaches various species of animals via food chain.
• Uses: Tetrodotoxin is a highly selective, reversible sodium channel blocker. TTX is an extremely popular chemical tool in the physiological and pharmacological laboratories since discovery of its channel blocking action in the early 1960s. Some potential therapeutic uses include suppressing pain in cancer patients, preventing ischemic damage of the brain that follows stroke, relieving the symptoms of withdrawal in opiate addicts, and using it as anesthetic agent.

Technology Process of 3-Amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.17,11.01,6]tetradec-3-ene-5,9,12,13,14-pentol

There total 62 articles about 3-Amino-14-(hydroxymethyl)-8,10-dioxa-2,4-diazatetracyclo[7.3.1.17,11.01,6]tetradec-3-ene-5,9,12,13,14-pentol which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 58.0%

C28H49N3O12Si → 4,9-anhydrotetrodotoxin + tetradotoxin (4368-28-9)

Guidance literature:

With trifluoroacetic acid; In water; at 20 ℃;

DOI:10.1002/anie.200460293

Reference yield:

[(2R,5S,6R)-2-Benzyloxymethoxy-4-(tert-butyl-diphenyl-silanyloxymethyl)-6-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-5-hydroxy-cyclohex-3-en-(E)-ylidene]-acetaldehyde (588693-73-6) → tetradotoxin (4368-28-9)

Guidance literature:

Multi-step reaction with 34 steps

1.1: 2-methyl-2-butene; aq. NaH₂PO₄; NaClO₂ / 2-methyl-propan-2-ol / 1 h / 20 °C

2.1: 1.60 g / benzene; methanol / 1 h / 20 °C

3.1: CH₂Cl₂ / 0.25 h / 0 °C

4.1: 1.68 g / K₂CO₃ / methanol / 10 h / 0 °C

5.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C

6.1: LiBH₄ / tetrahydrofuran / 3 h / 20 °C

7.1: pyridine / 10 h / 50 °C

8.1: 2.15 g / Et₃N; DMAP / tetrahydrofuran / 48 h / 20 °C

9.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C

10.1: 98 percent / Na₂HPO₄; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C

11.1: 95 percent / Et₃N / CH₂Cl₂ / 0.67 h / -42 °C

12.1: Ac₂O; DMSO / 2 h / 20 °C

13.1: 1.04 g / NaBH₄ / methanol / 0.25 h / 0 °C

14.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C

15.1: 89 percent / TFA / methanol / 3 h / 20 °C

16.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C

17.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C

18.1: NMO; OsO₄ / acetone; H₂O / 3 h / 20 °C

19.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C

20.1: NaBH₄ / methanol / 0.25 h / -78 °C

21.1: Et₃N; MeOH / 28.8 h / 15 °C

22.1: pyridine; Et₃N / CH₂Cl₂ / 0.5 h / 0 °C

22.2: pyridine; DMAP / CH₂Cl₂ / 2 h / 20 °C

23.1: Pd(OH)2/C / methanol / 12 h / 20 °C

24.1: 96 mg / DMAP / pyridine / 2 h / 20 °C

25.1: 75 percent / aq. TFA / methanol; H₂O / 26.4 h / 20 °C

26.1: CAN / acetonitrile; H₂O / 2 h / 85 °C

27.1: 38.5 mg / Et₃N; HgCl₂ / dimethylformamide / 2 h / 20 °C

28.1: NaIO₄ / methanol; H₂O / 0.5 h / 20 °C

29.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C

30.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C

31.1: HCl; dioxane / 24 h

32.1: 11.2 mg / Et₃N / pyridine / 12 h / 40 °C

33.1: 18 percent / Et₃N / aq. methanol / 8 h / 20 °C

34.1: 63 percent / trifluoroacetic acid; D₂O / 96 h

With pyridine; hydrogenchloride; methanol; dmap; lithium hydroxide; sodium chlorite; sodium tetrahydroborate; sodium periodate; disodium hydrogenphosphate; sodium dihydrogenphosphate; osmium(VIII) oxide; lithium borohydride; N-methyl-2-indolinone; 2-methyl-but-2-ene; ammonium cerium(IV) nitrate; potassium tert-butylate; acetic anhydride; potassium carbonate; dimethyl sulfoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; 3-chloro-benzenecarboperoxoic acid; trifluoroacetic acid; mercury dichloride; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione; palladium dihydroxide; In tetrahydrofuran; 1,4-dioxane; pyridine; hydrogenchloride; methanol; dichloromethane; water; water-d2; dimethyl sulfoxide; 1,2-dichloro-ethane; N,N-dimethyl-formamide; 1,2-dichloro-benzene; acetone; acetonitrile; trifluoroacetic acid; tert-butyl alcohol; benzene; 12.1: Albright-Goldman reaction;

DOI:10.1021/ja0342998

Reference yield:

(1S,4R,6R)-4-Benzyloxymethoxy-2-(tert-butyl-diphenyl-silanyloxymethyl)-6-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-5-[2-hydroxy-eth-(E)-ylidene]-cyclohex-2-enol (588693-71-4) → tetradotoxin (4368-28-9)

Guidance literature:

Multi-step reaction with 35 steps

1.1: 94 percent / K₂CO₃; Bu₄NCl; NCS / TEMPO / CH₂Cl₂; aq. NaHCO₃ / 0.5 h / 20 °C

2.1: 2-methyl-2-butene; aq. NaH₂PO₄; NaClO₂ / 2-methyl-propan-2-ol / 1 h / 20 °C

3.1: 1.60 g / benzene; methanol / 1 h / 20 °C

4.1: CH₂Cl₂ / 0.25 h / 0 °C

5.1: 1.68 g / K₂CO₃ / methanol / 10 h / 0 °C

6.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C

7.1: LiBH₄ / tetrahydrofuran / 3 h / 20 °C

8.1: pyridine / 10 h / 50 °C

9.1: 2.15 g / Et₃N; DMAP / tetrahydrofuran / 48 h / 20 °C

10.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C

11.1: 98 percent / Na₂HPO₄; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C

12.1: 95 percent / Et₃N / CH₂Cl₂ / 0.67 h / -42 °C

13.1: Ac₂O; DMSO / 2 h / 20 °C

14.1: 1.04 g / NaBH₄ / methanol / 0.25 h / 0 °C

15.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C

16.1: 89 percent / TFA / methanol / 3 h / 20 °C

17.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C

18.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C

19.1: NMO; OsO₄ / acetone; H₂O / 3 h / 20 °C

20.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C

21.1: NaBH₄ / methanol / 0.25 h / -78 °C

22.1: Et₃N; MeOH / 28.8 h / 15 °C

23.1: pyridine; Et₃N / CH₂Cl₂ / 0.5 h / 0 °C

23.2: pyridine; DMAP / CH₂Cl₂ / 2 h / 20 °C

24.1: Pd(OH)2/C / methanol / 12 h / 20 °C

25.1: 96 mg / DMAP / pyridine / 2 h / 20 °C

26.1: 75 percent / aq. TFA / methanol; H₂O / 26.4 h / 20 °C

27.1: CAN / acetonitrile; H₂O / 2 h / 85 °C

28.1: 38.5 mg / Et₃N; HgCl₂ / dimethylformamide / 2 h / 20 °C

29.1: NaIO₄ / methanol; H₂O / 0.5 h / 20 °C

30.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C

31.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C

32.1: HCl; dioxane / 24 h

33.1: 11.2 mg / Et₃N / pyridine / 12 h / 40 °C

34.1: 18 percent / Et₃N / aq. methanol / 8 h / 20 °C

35.1: 63 percent / trifluoroacetic acid; D₂O / 96 h

With pyridine; hydrogenchloride; methanol; dmap; lithium hydroxide; sodium chlorite; sodium tetrahydroborate; sodium periodate; disodium hydrogenphosphate; sodium dihydrogenphosphate; N-chloro-succinimide; osmium(VIII) oxide; lithium borohydride; N-methyl-2-indolinone; 2-methyl-but-2-ene; ammonium cerium(IV) nitrate; potassium tert-butylate; tetrabutyl-ammonium chloride; acetic anhydride; potassium carbonate; dimethyl sulfoxide; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; 3-chloro-benzenecarboperoxoic acid; trifluoroacetic acid; mercury dichloride; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione; 2,2,6,6-tetramethyl-piperidine-N-oxyl; palladium dihydroxide; In tetrahydrofuran; 1,4-dioxane; pyridine; hydrogenchloride; methanol; dichloromethane; water; water-d2; sodium hydrogencarbonate; dimethyl sulfoxide; 1,2-dichloro-ethane; N,N-dimethyl-formamide; 1,2-dichloro-benzene; acetone; acetonitrile; trifluoroacetic acid; tert-butyl alcohol; benzene; 13.1: Albright-Goldman reaction;

DOI:10.1021/ja0342998

upstream raw materials:

Acetic acid (1R,3S,5S,6S,7S,8R,9S,10S)-9-acetoxy-9-acetoxymethyl-8-dimethoxymethyl-3,10-dihydroxy-7-(2,2,2-trichloro-acetylamino)-2,4-dioxa-tricyclo[3.3.1.1^3,7]dec-6-yl ester

2,2,2-Trichloro-N-[(1R,2S,5R,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4-methyl-5,6-bis-triethylsilanyloxy-1-vinyl-cyclohex-3-enyl]-acetamide

C₂₅H₃₆Cl₃NO₁₂Si

Acetic acid (1R,3S,5S,6S,7R,8R,9S,10S)-3,6,9-triacetoxy-9-acetoxymethyl-8-dimethoxymethyl-7-(2,2,2-trichloro-acetylamino)-2,4-dioxa-tricyclo[3.3.1.1^3,7]dec-10-yl ester

Downstream raw materials:

Diacetyl-anhydro-epitetrodotoxin

11-nortetrodotoxin-6-ol

C₁₁H₁₅N₃O₈

Tetrodosaeure

Refernces

• 1、 Nishikawa, Toshio,Urabe, Daisuke,Isobe, Minoru. "An efficient total synthesis of optically active tetrodotoxin". . p. 4782 - 4785. Retrieved 2007/10/03.
• 2、 Khora, Samanta S.,Yasumoto, Takeshi. "ISOLATION OF 11-OXOTETRODOTOXIN FROM THE PUFFER AROTHRON NIGROPUNCTATUS". . p. 4393 - 4394. Retrieved 2007/10/02.