Product Name

  • Name

    TETRODOTOXIN

  • EINECS 224-458-8
  • CAS No. 4368-28-9
  • Article Data3
  • CAS DataBase
  • Density 2.78 g/cm3
  • Solubility slightly soluble in Water
  • Melting Point 225oC dec
  • Formula C11H17N3O8
  • Boiling Point 702.6 °C at 760 mmHg
  • Molecular Weight 319.271
  • Flash Point 378.7 °C
  • Transport Information UN 3462 6.1/PG 1
  • Appearance white powder
  • Safety 22-36/37/39-45
  • Risk Codes 26/27/28
  • Molecular Structure Molecular Structure of 4368-28-9 (TETRODOTOXIN)
  • Hazard Symbols VeryT+
  • Synonyms 8a(1H)-Quinazolineorthoglycolicacid, octahydro-4,5,6,7,8-pentahydroxy-6-(hydroxymethyl)-2-imino-, cyclic8a,5:8a,7-ester (7CI);Tetrodotoxin (8CI);(-)-Tetrodotoxin;5,9:7,10a-Dimethano-10aH-[1,3]dioxocino[6,5-d]pyrimidine-4,7,10,11,12-pentol,octahydro-12-(hydroxymethyl)-2-imino-, [4R-(4a,4aa,5a,7a,9a,10a,10ab,11S*,12S*)]-;Araregai toxin;BJT 1;Babyloniajaponica toxin 1;Maculotoxin;PFT-1 Toxin;Spheroidine;TTX;Tarichatoxin;Tetrodotoxine;[4R-(4a,4aa,5a,7a,9a,10a,10ab,11S*,12S*)]-Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano-10aH-[1,3]dioxocino[6,5-d]pyrimidine-4,7,10,11,12-pentol;
  • PSA 192.32000
  • LogP -6.03400

Synthetic route

C19H23N3O10

C19H23N3O10

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 3h;96.4%
4-O-methyltetrodotoxin

4-O-methyltetrodotoxin

A

tetradotoxin
4368-28-9

tetradotoxin

B

4,9-anhydro-4-epitetrodotoxin

4,9-anhydro-4-epitetrodotoxin

Conditions
ConditionsYield
In water-d2; trifluoroacetic acid for 96h;A 66%
B 15%
4,9-anhydro-4-epitetrodotoxin

4,9-anhydro-4-epitetrodotoxin

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
In water-d2; trifluoroacetic acid for 96h;63%
C28H49N3O12Si

C28H49N3O12Si

A

4,9-anhydrotetrodotoxin

4,9-anhydrotetrodotoxin

B

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
With trifluoroacetic acid In water at 20℃;A 58%
B 36%
C17H31NO8Si

C17H31NO8Si

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: HgCl2; Et3N / dimethylformamide / 20 °C
2: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
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[3.3.1.13,7]dec-6-yl ester
794568-31-3

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[3.3.1.13,7]dec-6-yl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: 2,6-lutidine / CH2Cl2 / 0 °C
2: diisobutylaluminum hydride / CH2Cl2 / -40 °C
3: HgCl2; Et3N / dimethylformamide / 20 °C
4: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
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
794568-18-6

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

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 16 steps
1.1: selenium dioxide; pyridine N-oxide / dioxane / Heating
1.2: 48 percent / NaBH4; CeCl3*7H2O / methanol / 0 °C
2.1: 2,6-lutidine / CH2Cl2 / 0 °C
2.2: 83 percent / m-chloroperbenzoic acid; Na2HPO4 / CH2Cl2 / 20 °C
3.1: 90 percent / O3; Et3N / CH2Cl2 / -78 °C
4.1: 70 percent / EtMgBr / tetrahydrofuran / 0 °C
5.1: 4-dimethylaminopyridine / pyridine / 20 °C
5.2: 91 percent / tetrabutylammonium fluoride / tetrahydrofuran / -10 °C
6.1: KMnO4; NaIO4; NaHCO3 / 2-methyl-propan-2-ol; H2O / 50 °C
7.1: H2O2; NaHCO3 / methanol / 20 °C
8.1: 2,6-lutidine / CH2Cl2 / -40 °C
9.1: pyridine / 20 °C
10.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
10.2: 71 percent / pyridine / 20 °C
11.1: periodic acid / methyl acetate / 20 °C
11.2: camphor sulfonic acid / methanol / 20 °C
12.1: aq. NH3 / methanol / 0 °C
13.1: 2,6-lutidine / CH2Cl2 / 0 °C
14.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
15.1: HgCl2; Et3N / dimethylformamide / 20 °C
16.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
C25H36Cl3NO12Si
794568-32-4

C25H36Cl3NO12Si

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
2: HgCl2; Et3N / dimethylformamide / 20 °C
3: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
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[3.3.1.13,7]dec-10-yl ester
794568-30-2

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[3.3.1.13,7]dec-10-yl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: aq. NH3 / methanol / 0 °C
2: 2,6-lutidine / CH2Cl2 / 0 °C
3: diisobutylaluminum hydride / CH2Cl2 / -40 °C
4: HgCl2; Et3N / dimethylformamide / 20 °C
5: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
2,2,2-Trichloro-N-[(1R,2S,5R,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4-hydroxymethyl-5,6-bis-triethylsilanyloxy-1-vinyl-cyclohex-3-enyl]-acetamide
794568-19-7

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

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 15 steps
1.1: 2,6-lutidine / CH2Cl2 / 0 °C
1.2: 83 percent / m-chloroperbenzoic acid; Na2HPO4 / CH2Cl2 / 20 °C
2.1: 90 percent / O3; Et3N / CH2Cl2 / -78 °C
3.1: 70 percent / EtMgBr / tetrahydrofuran / 0 °C
4.1: 4-dimethylaminopyridine / pyridine / 20 °C
4.2: 91 percent / tetrabutylammonium fluoride / tetrahydrofuran / -10 °C
5.1: KMnO4; NaIO4; NaHCO3 / 2-methyl-propan-2-ol; H2O / 50 °C
6.1: H2O2; NaHCO3 / methanol / 20 °C
7.1: 2,6-lutidine / CH2Cl2 / -40 °C
8.1: pyridine / 20 °C
9.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
9.2: 71 percent / pyridine / 20 °C
10.1: periodic acid / methyl acetate / 20 °C
10.2: camphor sulfonic acid / methanol / 20 °C
11.1: aq. NH3 / methanol / 0 °C
12.1: 2,6-lutidine / CH2Cl2 / 0 °C
13.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
14.1: HgCl2; Et3N / dimethylformamide / 20 °C
15.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
Acetic acid (1R,3S,5S,6S,7R,8S,9S,10S)-3,6,9-triacetoxy-9-acetoxymethyl-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-7-(2,2,2-trichloro-acetylamino)-2,4-dioxa-tricyclo[3.3.1.13,7]dec-10-yl ester
794568-29-9

Acetic acid (1R,3S,5S,6S,7R,8S,9S,10S)-3,6,9-triacetoxy-9-acetoxymethyl-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-7-(2,2,2-trichloro-acetylamino)-2,4-dioxa-tricyclo[3.3.1.13,7]dec-10-yl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1.1: periodic acid / methyl acetate / 20 °C
1.2: camphor sulfonic acid / methanol / 20 °C
2.1: aq. NH3 / methanol / 0 °C
3.1: 2,6-lutidine / CH2Cl2 / 0 °C
4.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
5.1: HgCl2; Et3N / dimethylformamide / 20 °C
6.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
2,2,2-Trichloro-N-[(1R,4S,5S,6S,7S,8S,9S)-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4,8-dihydroxy-8-hydroxymethyl-3-oxo-6,7-bis-triethylsilanyloxy-2-oxa-bicyclo[3.3.1]non-5-yl]-acetamide

2,2,2-Trichloro-N-[(1R,4S,5S,6S,7S,8S,9S)-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4,8-dihydroxy-8-hydroxymethyl-3-oxo-6,7-bis-triethylsilanyloxy-2-oxa-bicyclo[3.3.1]non-5-yl]-acetamide

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 9 steps
1.1: 2,6-lutidine / CH2Cl2 / -40 °C
2.1: pyridine / 20 °C
3.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
3.2: 71 percent / pyridine / 20 °C
4.1: periodic acid / methyl acetate / 20 °C
4.2: camphor sulfonic acid / methanol / 20 °C
5.1: aq. NH3 / methanol / 0 °C
6.1: 2,6-lutidine / CH2Cl2 / 0 °C
7.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
8.1: HgCl2; Et3N / dimethylformamide / 20 °C
9.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
2,2,2-Trichloro-N-[(1S,2S,3R,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-formyl-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-acetamide
794568-21-1

2,2,2-Trichloro-N-[(1S,2S,3R,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-formyl-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-acetamide

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 13 steps
1.1: 70 percent / EtMgBr / tetrahydrofuran / 0 °C
2.1: 4-dimethylaminopyridine / pyridine / 20 °C
2.2: 91 percent / tetrabutylammonium fluoride / tetrahydrofuran / -10 °C
3.1: KMnO4; NaIO4; NaHCO3 / 2-methyl-propan-2-ol; H2O / 50 °C
4.1: H2O2; NaHCO3 / methanol / 20 °C
5.1: 2,6-lutidine / CH2Cl2 / -40 °C
6.1: pyridine / 20 °C
7.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
7.2: 71 percent / pyridine / 20 °C
8.1: periodic acid / methyl acetate / 20 °C
8.2: camphor sulfonic acid / methanol / 20 °C
9.1: aq. NH3 / methanol / 0 °C
10.1: 2,6-lutidine / CH2Cl2 / 0 °C
11.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
12.1: HgCl2; Et3N / dimethylformamide / 20 °C
13.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
2,2,2-Trichloro-N-[(1S,2S,3R,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-3-vinyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-acetamide
947178-10-1

2,2,2-Trichloro-N-[(1S,2S,3R,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-3-vinyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-acetamide

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 14 steps
1.1: 90 percent / O3; Et3N / CH2Cl2 / -78 °C
2.1: 70 percent / EtMgBr / tetrahydrofuran / 0 °C
3.1: 4-dimethylaminopyridine / pyridine / 20 °C
3.2: 91 percent / tetrabutylammonium fluoride / tetrahydrofuran / -10 °C
4.1: KMnO4; NaIO4; NaHCO3 / 2-methyl-propan-2-ol; H2O / 50 °C
5.1: H2O2; NaHCO3 / methanol / 20 °C
6.1: 2,6-lutidine / CH2Cl2 / -40 °C
7.1: pyridine / 20 °C
8.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
8.2: 71 percent / pyridine / 20 °C
9.1: periodic acid / methyl acetate / 20 °C
9.2: camphor sulfonic acid / methanol / 20 °C
10.1: aq. NH3 / methanol / 0 °C
11.1: 2,6-lutidine / CH2Cl2 / 0 °C
12.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
13.1: HgCl2; Et3N / dimethylformamide / 20 °C
14.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
Acetic acid (R)-1-[(1S,2S,3S,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-(2,2,2-trichloro-acetylamino)-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-prop-2-ynyl ester
794568-23-3

Acetic acid (R)-1-[(1S,2S,3S,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-(2,2,2-trichloro-acetylamino)-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-prop-2-ynyl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 11 steps
1.1: KMnO4; NaIO4; NaHCO3 / 2-methyl-propan-2-ol; H2O / 50 °C
2.1: H2O2; NaHCO3 / methanol / 20 °C
3.1: 2,6-lutidine / CH2Cl2 / -40 °C
4.1: pyridine / 20 °C
5.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
5.2: 71 percent / pyridine / 20 °C
6.1: periodic acid / methyl acetate / 20 °C
6.2: camphor sulfonic acid / methanol / 20 °C
7.1: aq. NH3 / methanol / 0 °C
8.1: 2,6-lutidine / CH2Cl2 / 0 °C
9.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
10.1: HgCl2; Et3N / dimethylformamide / 20 °C
11.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
2,2,2-Trichloro-N-[(1R,4S,5S,6S,7S,8S,9S)-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4,8-dihydroxy-3-oxo-6,7-bis-triethylsilanyloxy-8-triethylsilanyloxymethyl-2-oxa-bicyclo[3.3.1]non-5-yl]-acetamide
794568-26-6

2,2,2-Trichloro-N-[(1R,4S,5S,6S,7S,8S,9S)-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4,8-dihydroxy-3-oxo-6,7-bis-triethylsilanyloxy-8-triethylsilanyloxymethyl-2-oxa-bicyclo[3.3.1]non-5-yl]-acetamide

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1.1: pyridine / 20 °C
2.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
2.2: 71 percent / pyridine / 20 °C
3.1: periodic acid / methyl acetate / 20 °C
3.2: camphor sulfonic acid / methanol / 20 °C
4.1: aq. NH3 / methanol / 0 °C
5.1: 2,6-lutidine / CH2Cl2 / 0 °C
6.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
7.1: HgCl2; Et3N / dimethylformamide / 20 °C
8.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
Acetic acid (1R,4S,5S,6S,7S,8S,9S)-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-8-hydroxy-3-oxo-5-(2,2,2-trichloro-acetylamino)-6,7-bis-triethylsilanyloxy-8-triethylsilanyloxymethyl-2-oxa-bicyclo[3.3.1]non-4-yl ester
794568-28-8

Acetic acid (1R,4S,5S,6S,7S,8S,9S)-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-8-hydroxy-3-oxo-5-(2,2,2-trichloro-acetylamino)-6,7-bis-triethylsilanyloxy-8-triethylsilanyloxymethyl-2-oxa-bicyclo[3.3.1]non-4-yl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
1.2: 71 percent / pyridine / 20 °C
2.1: periodic acid / methyl acetate / 20 °C
2.2: camphor sulfonic acid / methanol / 20 °C
3.1: aq. NH3 / methanol / 0 °C
4.1: 2,6-lutidine / CH2Cl2 / 0 °C
5.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
6.1: HgCl2; Et3N / dimethylformamide / 20 °C
7.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
2,2,2-Trichloro-N-[(1S,2S,3S,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-((R)-1-hydroxy-3-trimethylsilanyl-prop-2-ynyl)-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-acetamide
794568-22-2

2,2,2-Trichloro-N-[(1S,2S,3S,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-((R)-1-hydroxy-3-trimethylsilanyl-prop-2-ynyl)-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-acetamide

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 12 steps
1.1: 4-dimethylaminopyridine / pyridine / 20 °C
1.2: 91 percent / tetrabutylammonium fluoride / tetrahydrofuran / -10 °C
2.1: KMnO4; NaIO4; NaHCO3 / 2-methyl-propan-2-ol; H2O / 50 °C
3.1: H2O2; NaHCO3 / methanol / 20 °C
4.1: 2,6-lutidine / CH2Cl2 / -40 °C
5.1: pyridine / 20 °C
6.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
6.2: 71 percent / pyridine / 20 °C
7.1: periodic acid / methyl acetate / 20 °C
7.2: camphor sulfonic acid / methanol / 20 °C
8.1: aq. NH3 / methanol / 0 °C
9.1: 2,6-lutidine / CH2Cl2 / 0 °C
10.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
11.1: HgCl2; Et3N / dimethylformamide / 20 °C
12.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
(S)-3-Acetoxy-3-[(1S,2S,3S,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-(2,2,2-trichloro-acetylamino)-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-2-oxo-propionic acid
794568-24-4

(S)-3-Acetoxy-3-[(1S,2S,3S,4S,5S,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-3-(2,2,2-trichloro-acetylamino)-4,5-bis-triethylsilanyloxy-6-triethylsilanyloxymethyl-7-oxa-bicyclo[4.1.0]hept-3-yl]-2-oxo-propionic acid

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1.1: H2O2; NaHCO3 / methanol / 20 °C
2.1: 2,6-lutidine / CH2Cl2 / -40 °C
3.1: pyridine / 20 °C
4.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
4.2: 71 percent / pyridine / 20 °C
5.1: periodic acid / methyl acetate / 20 °C
5.2: camphor sulfonic acid / methanol / 20 °C
6.1: aq. NH3 / methanol / 0 °C
7.1: 2,6-lutidine / CH2Cl2 / 0 °C
8.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
9.1: HgCl2; Et3N / dimethylformamide / 20 °C
10.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
2,2,2-Trichloro-N-[(1R,2S,5R,6S)-2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-5,6-dihydroxy-4-methyl-1-vinyl-cyclohex-3-enyl]-acetamide
444680-80-2

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

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 17 steps
1.1: 86 percent / pyridine / acetonitrile / 20 °C
2.1: selenium dioxide; pyridine N-oxide / dioxane / Heating
2.2: 48 percent / NaBH4; CeCl3*7H2O / methanol / 0 °C
3.1: 2,6-lutidine / CH2Cl2 / 0 °C
3.2: 83 percent / m-chloroperbenzoic acid; Na2HPO4 / CH2Cl2 / 20 °C
4.1: 90 percent / O3; Et3N / CH2Cl2 / -78 °C
5.1: 70 percent / EtMgBr / tetrahydrofuran / 0 °C
6.1: 4-dimethylaminopyridine / pyridine / 20 °C
6.2: 91 percent / tetrabutylammonium fluoride / tetrahydrofuran / -10 °C
7.1: KMnO4; NaIO4; NaHCO3 / 2-methyl-propan-2-ol; H2O / 50 °C
8.1: H2O2; NaHCO3 / methanol / 20 °C
9.1: 2,6-lutidine / CH2Cl2 / -40 °C
10.1: pyridine / 20 °C
11.1: tetrabutylammonium fluoride / acetonitrile / 0 °C
11.2: 71 percent / pyridine / 20 °C
12.1: periodic acid / methyl acetate / 20 °C
12.2: camphor sulfonic acid / methanol / 20 °C
13.1: aq. NH3 / methanol / 0 °C
14.1: 2,6-lutidine / CH2Cl2 / 0 °C
15.1: diisobutylaluminum hydride / CH2Cl2 / -40 °C
16.1: HgCl2; Et3N / dimethylformamide / 20 °C
17.1: 36 percent / trifluoroacetic acid / H2O / 20 °C
View Scheme
4-O-methyltetrodotoxin

4-O-methyltetrodotoxin

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 15 percent / trifluoroacetic acid; D2O / 96 h
2: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
[(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

[(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

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
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
View Scheme
Multi-step reaction with 35 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: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
34.1: 15 percent / trifluoroacetic acid; D2O / 96 h
35.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
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: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
34.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
(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

(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

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
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
View Scheme
Multi-step reaction with 36 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: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
35.1: 15 percent / trifluoroacetic acid; D2O / 96 h
36.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
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: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
35.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
[(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]-acetic acid methyl ester
588693-75-8

[(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]-acetic acid methyl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 32 steps
1.1: CH2Cl2 / 0.25 h / 0 °C
2.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
3.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
4.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
5.1: pyridine / 10 h / 50 °C
6.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
7.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
8.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
9.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
10.1: Ac2O; DMSO / 2 h / 20 °C
11.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
12.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
13.1: 89 percent / TFA / methanol / 3 h / 20 °C
14.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
15.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
16.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
17.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
18.1: NaBH4 / methanol / 0.25 h / -78 °C
19.1: Et3N; MeOH / 28.8 h / 15 °C
20.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
20.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
21.1: Pd(OH)2/C / methanol / 12 h / 20 °C
22.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
23.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
24.1: CAN / acetonitrile; H2O / 2 h / 85 °C
25.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
26.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
27.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
28.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
29.1: HCl; dioxane / 24 h
30.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
31.1: 18 percent / Et3N / aq. methanol / 8 h / 20 °C
32.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 33 steps
1.1: CH2Cl2 / 0.25 h / 0 °C
2.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
3.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
4.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
5.1: pyridine / 10 h / 50 °C
6.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
7.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
8.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
9.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
10.1: Ac2O; DMSO / 2 h / 20 °C
11.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
12.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
13.1: 89 percent / TFA / methanol / 3 h / 20 °C
14.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
15.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
16.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
17.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
18.1: NaBH4 / methanol / 0.25 h / -78 °C
19.1: Et3N; MeOH / 28.8 h / 15 °C
20.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
20.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
21.1: Pd(OH)2/C / methanol / 12 h / 20 °C
22.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
23.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
24.1: CAN / acetonitrile; H2O / 2 h / 85 °C
25.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
26.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
27.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
28.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
29.1: HCl; dioxane / 24 h
30.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
31.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
32.1: 15 percent / trifluoroacetic acid; D2O / 96 h
33.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 32 steps
1.1: CH2Cl2 / 0.25 h / 0 °C
2.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
3.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
4.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
5.1: pyridine / 10 h / 50 °C
6.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
7.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
8.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
9.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
10.1: Ac2O; DMSO / 2 h / 20 °C
11.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
12.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
13.1: 89 percent / TFA / methanol / 3 h / 20 °C
14.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
15.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
16.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
17.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
18.1: NaBH4 / methanol / 0.25 h / -78 °C
19.1: Et3N; MeOH / 28.8 h / 15 °C
20.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
20.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
21.1: Pd(OH)2/C / methanol / 12 h / 20 °C
22.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
23.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
24.1: CAN / acetonitrile; H2O / 2 h / 85 °C
25.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
26.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
27.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
28.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
29.1: HCl; dioxane / 24 h
30.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
31.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
32.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
[(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]-acetic acid

[(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]-acetic acid

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 33 steps
1.1: 1.60 g / benzene; methanol / 1 h / 20 °C
2.1: CH2Cl2 / 0.25 h / 0 °C
3.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
4.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
5.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
6.1: pyridine / 10 h / 50 °C
7.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
8.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
9.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
10.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
11.1: Ac2O; DMSO / 2 h / 20 °C
12.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
13.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
14.1: 89 percent / TFA / methanol / 3 h / 20 °C
15.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
16.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
17.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
18.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
19.1: NaBH4 / methanol / 0.25 h / -78 °C
20.1: Et3N; MeOH / 28.8 h / 15 °C
21.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
21.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
22.1: Pd(OH)2/C / methanol / 12 h / 20 °C
23.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
24.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
25.1: CAN / acetonitrile; H2O / 2 h / 85 °C
26.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
27.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
28.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
29.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
30.1: HCl; dioxane / 24 h
31.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
32.1: 18 percent / Et3N / aq. methanol / 8 h / 20 °C
33.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 34 steps
1.1: 1.60 g / benzene; methanol / 1 h / 20 °C
2.1: CH2Cl2 / 0.25 h / 0 °C
3.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
4.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
5.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
6.1: pyridine / 10 h / 50 °C
7.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
8.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
9.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
10.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
11.1: Ac2O; DMSO / 2 h / 20 °C
12.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
13.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
14.1: 89 percent / TFA / methanol / 3 h / 20 °C
15.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
16.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
17.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
18.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
19.1: NaBH4 / methanol / 0.25 h / -78 °C
20.1: Et3N; MeOH / 28.8 h / 15 °C
21.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
21.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
22.1: Pd(OH)2/C / methanol / 12 h / 20 °C
23.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
24.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
25.1: CAN / acetonitrile; H2O / 2 h / 85 °C
26.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
27.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
28.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
29.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
30.1: HCl; dioxane / 24 h
31.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
32.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
33.1: 15 percent / trifluoroacetic acid; D2O / 96 h
34.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 33 steps
1.1: 1.60 g / benzene; methanol / 1 h / 20 °C
2.1: CH2Cl2 / 0.25 h / 0 °C
3.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
4.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
5.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
6.1: pyridine / 10 h / 50 °C
7.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
8.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
9.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
10.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
11.1: Ac2O; DMSO / 2 h / 20 °C
12.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
13.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
14.1: 89 percent / TFA / methanol / 3 h / 20 °C
15.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
16.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
17.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
18.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
19.1: NaBH4 / methanol / 0.25 h / -78 °C
20.1: Et3N; MeOH / 28.8 h / 15 °C
21.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
21.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
22.1: Pd(OH)2/C / methanol / 12 h / 20 °C
23.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
24.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
25.1: CAN / acetonitrile; H2O / 2 h / 85 °C
26.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
27.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
28.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
29.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
30.1: HCl; dioxane / 24 h
31.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
32.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
33.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Benzoic acid (1S,2R,3S,4R,5S,6R)-2-acetoxy-5-benzyloxymethoxy-4-tert-butoxycarbonylamino-3-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4-(2-oxo-ethyl)-7-oxa-bicyclo[4.1.0]hept-1-ylmethyl ester
588693-98-5

Benzoic acid (1S,2R,3S,4R,5S,6R)-2-acetoxy-5-benzyloxymethoxy-4-tert-butoxycarbonylamino-3-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-4-(2-oxo-ethyl)-7-oxa-bicyclo[4.1.0]hept-1-ylmethyl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 18 steps
1.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
2.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
3.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
4.1: NaBH4 / methanol / 0.25 h / -78 °C
5.1: Et3N; MeOH / 28.8 h / 15 °C
6.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
6.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
7.1: Pd(OH)2/C / methanol / 12 h / 20 °C
8.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
9.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
10.1: CAN / acetonitrile; H2O / 2 h / 85 °C
11.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
12.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
13.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
14.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
15.1: HCl; dioxane / 24 h
16.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
17.1: 18 percent / Et3N / aq. methanol / 8 h / 20 °C
18.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 19 steps
1.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
2.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
3.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
4.1: NaBH4 / methanol / 0.25 h / -78 °C
5.1: Et3N; MeOH / 28.8 h / 15 °C
6.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
6.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
7.1: Pd(OH)2/C / methanol / 12 h / 20 °C
8.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
9.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
10.1: CAN / acetonitrile; H2O / 2 h / 85 °C
11.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
12.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
13.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
14.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
15.1: HCl; dioxane / 24 h
16.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
17.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
18.1: 15 percent / trifluoroacetic acid; D2O / 96 h
19.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 18 steps
1.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
2.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
3.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
4.1: NaBH4 / methanol / 0.25 h / -78 °C
5.1: Et3N; MeOH / 28.8 h / 15 °C
6.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
6.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
7.1: Pd(OH)2/C / methanol / 12 h / 20 °C
8.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
9.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
10.1: CAN / acetonitrile; H2O / 2 h / 85 °C
11.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
12.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
13.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
14.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
15.1: HCl; dioxane / 24 h
16.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
17.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
18.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Benzoic acid (1S,5R,8S,8aR)-5-benzyloxymethoxy-7-(tert-butyl-diphenyl-silanyloxymethyl)-1-hydroxymethyl-3-methoxy-3,5,8,8a-tetrahydro-1H-isochromen-8-yl ester

Benzoic acid (1S,5R,8S,8aR)-5-benzyloxymethoxy-7-(tert-butyl-diphenyl-silanyloxymethyl)-1-hydroxymethyl-3-methoxy-3,5,8,8a-tetrahydro-1H-isochromen-8-yl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 41 steps
1.1: 12.80 g / DMAP / pyridine / 3 h / 20 °C
2.1: 1.60 g / aq. PPTS; HgO / acetone / 7 h / 55 °C
3.1: Mg(OEt)2 / methanol; ethyl acetate / 1 h / 20 °C
4.1: NaBH4 / methanol / 0.25 h / 20 °C
5.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
5.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
6.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
7.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
8.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
9.1: 1.60 g / benzene; methanol / 1 h / 20 °C
10.1: CH2Cl2 / 0.25 h / 0 °C
11.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
12.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
13.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
14.1: pyridine / 10 h / 50 °C
15.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
16.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
17.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
18.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
19.1: Ac2O; DMSO / 2 h / 20 °C
20.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
21.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
22.1: 89 percent / TFA / methanol / 3 h / 20 °C
23.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
24.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
25.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
26.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
27.1: NaBH4 / methanol / 0.25 h / -78 °C
28.1: Et3N; MeOH / 28.8 h / 15 °C
29.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
29.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
30.1: Pd(OH)2/C / methanol / 12 h / 20 °C
31.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
32.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
33.1: CAN / acetonitrile; H2O / 2 h / 85 °C
34.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
35.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
36.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
37.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
38.1: HCl; dioxane / 24 h
39.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
40.1: 18 percent / Et3N / aq. methanol / 8 h / 20 °C
41.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 42 steps
1.1: 12.80 g / DMAP / pyridine / 3 h / 20 °C
2.1: 1.60 g / aq. PPTS; HgO / acetone / 7 h / 55 °C
3.1: Mg(OEt)2 / methanol; ethyl acetate / 1 h / 20 °C
4.1: NaBH4 / methanol / 0.25 h / 20 °C
5.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
5.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
6.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
7.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
8.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
9.1: 1.60 g / benzene; methanol / 1 h / 20 °C
10.1: CH2Cl2 / 0.25 h / 0 °C
11.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
12.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
13.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
14.1: pyridine / 10 h / 50 °C
15.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
16.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
17.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
18.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
19.1: Ac2O; DMSO / 2 h / 20 °C
20.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
21.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
22.1: 89 percent / TFA / methanol / 3 h / 20 °C
23.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
24.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
25.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
26.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
27.1: NaBH4 / methanol / 0.25 h / -78 °C
28.1: Et3N; MeOH / 28.8 h / 15 °C
29.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
29.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
30.1: Pd(OH)2/C / methanol / 12 h / 20 °C
31.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
32.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
33.1: CAN / acetonitrile; H2O / 2 h / 85 °C
34.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
35.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
36.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
37.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
38.1: HCl; dioxane / 24 h
39.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
40.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
41.1: 15 percent / trifluoroacetic acid; D2O / 96 h
42.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 41 steps
1.1: 12.80 g / DMAP / pyridine / 3 h / 20 °C
2.1: 1.60 g / aq. PPTS; HgO / acetone / 7 h / 55 °C
3.1: Mg(OEt)2 / methanol; ethyl acetate / 1 h / 20 °C
4.1: NaBH4 / methanol / 0.25 h / 20 °C
5.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
5.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
6.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
7.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
8.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
9.1: 1.60 g / benzene; methanol / 1 h / 20 °C
10.1: CH2Cl2 / 0.25 h / 0 °C
11.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
12.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
13.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
14.1: pyridine / 10 h / 50 °C
15.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
16.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
17.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
18.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
19.1: Ac2O; DMSO / 2 h / 20 °C
20.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
21.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
22.1: 89 percent / TFA / methanol / 3 h / 20 °C
23.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
24.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
25.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
26.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
27.1: NaBH4 / methanol / 0.25 h / -78 °C
28.1: Et3N; MeOH / 28.8 h / 15 °C
29.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
29.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
30.1: Pd(OH)2/C / methanol / 12 h / 20 °C
31.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
32.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
33.1: CAN / acetonitrile; H2O / 2 h / 85 °C
34.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
35.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
36.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
37.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
38.1: HCl; dioxane / 24 h
39.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
40.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
41.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
benzoic acid 1-(tert-butyl-dimethyl-silanyloxymethyl)-7-(tert-butyl-diphenyl-silanyloxymethyl)-5-hydroxy-3-methoxy-3,5,8,8a-tetrahydro-1H-isochromen-8-yl ester
588693-55-4

benzoic acid 1-(tert-butyl-dimethyl-silanyloxymethyl)-7-(tert-butyl-diphenyl-silanyloxymethyl)-5-hydroxy-3-methoxy-3,5,8,8a-tetrahydro-1H-isochromen-8-yl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 43 steps
1.1: i-Pr2NEt; DMAP / 1,2-dichloro-ethane / 4 h / 60 °C
2.1: (+/-)-CSA; MeOH / 1 h / 20 °C
3.1: 12.80 g / DMAP / pyridine / 3 h / 20 °C
4.1: 1.60 g / aq. PPTS; HgO / acetone / 7 h / 55 °C
5.1: Mg(OEt)2 / methanol; ethyl acetate / 1 h / 20 °C
6.1: NaBH4 / methanol / 0.25 h / 20 °C
7.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
7.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
8.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
9.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
10.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
11.1: 1.60 g / benzene; methanol / 1 h / 20 °C
12.1: CH2Cl2 / 0.25 h / 0 °C
13.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
14.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
15.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
16.1: pyridine / 10 h / 50 °C
17.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
18.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
19.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
20.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
21.1: Ac2O; DMSO / 2 h / 20 °C
22.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
23.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
24.1: 89 percent / TFA / methanol / 3 h / 20 °C
25.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
26.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
27.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
28.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
29.1: NaBH4 / methanol / 0.25 h / -78 °C
30.1: Et3N; MeOH / 28.8 h / 15 °C
31.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
31.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
32.1: Pd(OH)2/C / methanol / 12 h / 20 °C
33.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
34.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
35.1: CAN / acetonitrile; H2O / 2 h / 85 °C
36.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
37.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
38.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
39.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
40.1: HCl; dioxane / 24 h
41.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
42.1: 18 percent / Et3N / aq. methanol / 8 h / 20 °C
43.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 44 steps
1.1: i-Pr2NEt; DMAP / 1,2-dichloro-ethane / 4 h / 60 °C
2.1: (+/-)-CSA; MeOH / 1 h / 20 °C
3.1: 12.80 g / DMAP / pyridine / 3 h / 20 °C
4.1: 1.60 g / aq. PPTS; HgO / acetone / 7 h / 55 °C
5.1: Mg(OEt)2 / methanol; ethyl acetate / 1 h / 20 °C
6.1: NaBH4 / methanol / 0.25 h / 20 °C
7.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
7.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
8.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
9.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
10.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
11.1: 1.60 g / benzene; methanol / 1 h / 20 °C
12.1: CH2Cl2 / 0.25 h / 0 °C
13.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
14.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
15.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
16.1: pyridine / 10 h / 50 °C
17.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
18.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
19.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
20.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
21.1: Ac2O; DMSO / 2 h / 20 °C
22.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
23.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
24.1: 89 percent / TFA / methanol / 3 h / 20 °C
25.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
26.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
27.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
28.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
29.1: NaBH4 / methanol / 0.25 h / -78 °C
30.1: Et3N; MeOH / 28.8 h / 15 °C
31.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
31.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
32.1: Pd(OH)2/C / methanol / 12 h / 20 °C
33.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
34.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
35.1: CAN / acetonitrile; H2O / 2 h / 85 °C
36.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
37.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
38.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
39.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
40.1: HCl; dioxane / 24 h
41.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
42.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
43.1: 15 percent / trifluoroacetic acid; D2O / 96 h
44.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 43 steps
1.1: i-Pr2NEt; DMAP / 1,2-dichloro-ethane / 4 h / 60 °C
2.1: (+/-)-CSA; MeOH / 1 h / 20 °C
3.1: 12.80 g / DMAP / pyridine / 3 h / 20 °C
4.1: 1.60 g / aq. PPTS; HgO / acetone / 7 h / 55 °C
5.1: Mg(OEt)2 / methanol; ethyl acetate / 1 h / 20 °C
6.1: NaBH4 / methanol / 0.25 h / 20 °C
7.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
7.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
8.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
9.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
10.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
11.1: 1.60 g / benzene; methanol / 1 h / 20 °C
12.1: CH2Cl2 / 0.25 h / 0 °C
13.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
14.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
15.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
16.1: pyridine / 10 h / 50 °C
17.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
18.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
19.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
20.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
21.1: Ac2O; DMSO / 2 h / 20 °C
22.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
23.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
24.1: 89 percent / TFA / methanol / 3 h / 20 °C
25.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
26.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
27.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
28.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
29.1: NaBH4 / methanol / 0.25 h / -78 °C
30.1: Et3N; MeOH / 28.8 h / 15 °C
31.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
31.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
32.1: Pd(OH)2/C / methanol / 12 h / 20 °C
33.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
34.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
35.1: CAN / acetonitrile; H2O / 2 h / 85 °C
36.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
37.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
38.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
39.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
40.1: HCl; dioxane / 24 h
41.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
42.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
43.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Benzoic acid (1S,5R,8S,8aR)-5-benzyloxymethoxy-7-(tert-butyl-diphenyl-silanyloxymethyl)-3-hydroxy-1-hydroxymethyl-3,5,8,8a-tetrahydro-1H-isochromen-8-yl ester
588693-65-6

Benzoic acid (1S,5R,8S,8aR)-5-benzyloxymethoxy-7-(tert-butyl-diphenyl-silanyloxymethyl)-3-hydroxy-1-hydroxymethyl-3,5,8,8a-tetrahydro-1H-isochromen-8-yl ester

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 38 steps
1.1: NaBH4 / methanol / 0.25 h / 20 °C
2.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
2.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
3.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
4.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
5.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
6.1: 1.60 g / benzene; methanol / 1 h / 20 °C
7.1: CH2Cl2 / 0.25 h / 0 °C
8.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
9.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
10.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
11.1: pyridine / 10 h / 50 °C
12.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
13.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
14.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
15.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
16.1: Ac2O; DMSO / 2 h / 20 °C
17.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
18.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
19.1: 89 percent / TFA / methanol / 3 h / 20 °C
20.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
21.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
22.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
23.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
24.1: NaBH4 / methanol / 0.25 h / -78 °C
25.1: Et3N; MeOH / 28.8 h / 15 °C
26.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
26.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
27.1: Pd(OH)2/C / methanol / 12 h / 20 °C
28.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
29.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
30.1: CAN / acetonitrile; H2O / 2 h / 85 °C
31.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
32.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
33.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
34.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
35.1: HCl; dioxane / 24 h
36.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
37.1: 18 percent / Et3N / aq. methanol / 8 h / 20 °C
38.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 39 steps
1.1: NaBH4 / methanol / 0.25 h / 20 °C
2.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
2.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
3.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
4.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
5.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
6.1: 1.60 g / benzene; methanol / 1 h / 20 °C
7.1: CH2Cl2 / 0.25 h / 0 °C
8.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
9.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
10.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
11.1: pyridine / 10 h / 50 °C
12.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
13.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
14.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
15.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
16.1: Ac2O; DMSO / 2 h / 20 °C
17.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
18.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
19.1: 89 percent / TFA / methanol / 3 h / 20 °C
20.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
21.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
22.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
23.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
24.1: NaBH4 / methanol / 0.25 h / -78 °C
25.1: Et3N; MeOH / 28.8 h / 15 °C
26.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
26.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
27.1: Pd(OH)2/C / methanol / 12 h / 20 °C
28.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
29.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
30.1: CAN / acetonitrile; H2O / 2 h / 85 °C
31.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
32.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
33.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
34.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
35.1: HCl; dioxane / 24 h
36.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
37.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
38.1: 15 percent / trifluoroacetic acid; D2O / 96 h
39.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 38 steps
1.1: NaBH4 / methanol / 0.25 h / 20 °C
2.1: (+/-)-CSA / acetone / 0.67 h / 20 °C
2.2: 6.88 g / PPTS; MeOH / 0.08 h / 20 °C
3.1: 99 percent / DIBAL-H / CH2Cl2 / 0.25 h / -78 °C
4.1: 94 percent / K2CO3; Bu4NCl; NCS / TEMPO / CH2Cl2; aq. NaHCO3 / 0.5 h / 20 °C
5.1: 2-methyl-2-butene; aq. NaH2PO4; NaClO2 / 2-methyl-propan-2-ol / 1 h / 20 °C
6.1: 1.60 g / benzene; methanol / 1 h / 20 °C
7.1: CH2Cl2 / 0.25 h / 0 °C
8.1: 1.68 g / K2CO3 / methanol / 10 h / 0 °C
9.1: 90 percent / t-BuOK / tetrahydrofuran / 0.5 h / -78 - -15 °C
10.1: LiBH4 / tetrahydrofuran / 3 h / 20 °C
11.1: pyridine / 10 h / 50 °C
12.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
13.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
14.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
15.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
16.1: Ac2O; DMSO / 2 h / 20 °C
17.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
18.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
19.1: 89 percent / TFA / methanol / 3 h / 20 °C
20.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
21.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
22.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
23.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
24.1: NaBH4 / methanol / 0.25 h / -78 °C
25.1: Et3N; MeOH / 28.8 h / 15 °C
26.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
26.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
27.1: Pd(OH)2/C / methanol / 12 h / 20 °C
28.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
29.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
30.1: CAN / acetonitrile; H2O / 2 h / 85 °C
31.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
32.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
33.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
34.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
35.1: HCl; dioxane / 24 h
36.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
37.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
38.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
(1S,5R,6R,9R)-6-Benzyloxymethoxy-8-(tert-butyl-diphenyl-silanyloxymethyl)-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-5-(2-hydroxy-ethyl)-2-oxa-4-aza-bicyclo[3.3.1]non-7-en-3-one

(1S,5R,6R,9R)-6-Benzyloxymethoxy-8-(tert-butyl-diphenyl-silanyloxymethyl)-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-5-(2-hydroxy-ethyl)-2-oxa-4-aza-bicyclo[3.3.1]non-7-en-3-one

tetradotoxin
4368-28-9

tetradotoxin

Conditions
ConditionsYield
Multi-step reaction with 28 steps
1.1: pyridine / 10 h / 50 °C
2.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
3.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
4.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
5.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
6.1: Ac2O; DMSO / 2 h / 20 °C
7.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
8.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
9.1: 89 percent / TFA / methanol / 3 h / 20 °C
10.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
11.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
12.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
13.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
14.1: NaBH4 / methanol / 0.25 h / -78 °C
15.1: Et3N; MeOH / 28.8 h / 15 °C
16.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
16.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
17.1: Pd(OH)2/C / methanol / 12 h / 20 °C
18.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
19.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
20.1: CAN / acetonitrile; H2O / 2 h / 85 °C
21.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
22.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
23.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
24.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
25.1: HCl; dioxane / 24 h
26.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
27.1: 18 percent / Et3N / aq. methanol / 8 h / 20 °C
28.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 29 steps
1.1: pyridine / 10 h / 50 °C
2.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
3.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
4.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
5.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
6.1: Ac2O; DMSO / 2 h / 20 °C
7.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
8.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
9.1: 89 percent / TFA / methanol / 3 h / 20 °C
10.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
11.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
12.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
13.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
14.1: NaBH4 / methanol / 0.25 h / -78 °C
15.1: Et3N; MeOH / 28.8 h / 15 °C
16.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
16.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
17.1: Pd(OH)2/C / methanol / 12 h / 20 °C
18.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
19.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
20.1: CAN / acetonitrile; H2O / 2 h / 85 °C
21.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
22.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
23.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
24.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
25.1: HCl; dioxane / 24 h
26.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
27.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
28.1: 15 percent / trifluoroacetic acid; D2O / 96 h
29.1: 63 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
Multi-step reaction with 28 steps
1.1: pyridine / 10 h / 50 °C
2.1: 2.15 g / Et3N; DMAP / tetrahydrofuran / 48 h / 20 °C
3.1: 85 percent / aq. LiOH / methanol; 1,2-dichloro-ethane / 24 h / 40 °C
4.1: 98 percent / Na2HPO4; m-CPBA / 1,2-dichloro-ethane / 12 h / 20 °C
5.1: 95 percent / Et3N / CH2Cl2 / 0.67 h / -42 °C
6.1: Ac2O; DMSO / 2 h / 20 °C
7.1: 1.04 g / NaBH4 / methanol / 0.25 h / 0 °C
8.1: 100 percent / DMAP / pyridine / 1.5 h / 20 °C
9.1: 89 percent / TFA / methanol / 3 h / 20 °C
10.1: 100 percent / o-iodoxybenzoic acid / dimethylsulfoxide / 3 h / 20 °C
11.1: DBU / 1,2-dichloro-benzene / 0.33 h / 130 °C
12.1: NMO; OsO4 / acetone; H2O / 3 h / 20 °C
13.1: 141 mg / o-iodoxybenzoic acid / dimethylsulfoxide / 0.42 h / 55 °C
14.1: NaBH4 / methanol / 0.25 h / -78 °C
15.1: Et3N; MeOH / 28.8 h / 15 °C
16.1: pyridine; Et3N / CH2Cl2 / 0.5 h / 0 °C
16.2: pyridine; DMAP / CH2Cl2 / 2 h / 20 °C
17.1: Pd(OH)2/C / methanol / 12 h / 20 °C
18.1: 96 mg / DMAP / pyridine / 2 h / 20 °C
19.1: 75 percent / aq. TFA / methanol; H2O / 26.4 h / 20 °C
20.1: CAN / acetonitrile; H2O / 2 h / 85 °C
21.1: 38.5 mg / Et3N; HgCl2 / dimethylformamide / 2 h / 20 °C
22.1: NaIO4 / methanol; H2O / 0.5 h / 20 °C
23.1: 22.9 mg / TFA / methanol / 1.5 h / 20 °C
24.1: aq. HCl / tetrahydrofuran / 24 h / 20 °C
25.1: HCl; dioxane / 24 h
26.1: 11.2 mg / Et3N / pyridine / 12 h / 40 °C
27.1: 67 percent / Et3N / aq. methanol / 8 h / 20 °C
28.1: 66 percent / trifluoroacetic acid; D2O / 96 h
View Scheme
tetradotoxin
4368-28-9

tetradotoxin

acetone
67-64-1

acetone

A

6,11-O-isopropylidene-4,9-anhydrotetrodotoxin hydrochloride

6,11-O-isopropylidene-4,9-anhydrotetrodotoxin hydrochloride

B

6,11-O-isopropylidene-4,9-anhydrotetrodotoxin hydrochloride

6,11-O-isopropylidene-4,9-anhydrotetrodotoxin hydrochloride

Conditions
ConditionsYield
Stage #1: acetone With methanol; acetyl chloride at 20℃; for 0.5h;
Stage #2: tetradotoxin for 26 - 192h; Product distribution / selectivity;		A 22%
B 47%
...Expand
methanol
67-56-1

methanol

tetradotoxin
4368-28-9

tetradotoxin

acetone
67-64-1

acetone

4-O-methyl-6,11-O-isopropylidene-4,9-anhydrotetrodotoxin hydrochloride

4-O-methyl-6,11-O-isopropylidene-4,9-anhydrotetrodotoxin hydrochloride

Conditions
ConditionsYield
Stage #1: methanol; acetone With acetyl chloride at 20℃; for 0.5h;
Stage #2: tetradotoxin for 16h; Product distribution / selectivity;		45%
...Expand
acetic anhydride
108-24-7

acetic anhydride

tetradotoxin
4368-28-9

tetradotoxin

(5S)-8t-acetoxy-8c-acetoxymethyl-2-amino-(3at,7at,10bt)-3a,7a,8,9,10,10b-hexahydro-1(3)H-5r,10ac-cyclo-6c,9c-epioxido-[1,4]dioxepino[5,6,7-de]quinazoline-6,10c-diol
13285-84-2

(5S)-8t-acetoxy-8c-acetoxymethyl-2-amino-(3at,7at,10bt)-3a,7a,8,9,10,10b-hexahydro-1(3)H-5r,10ac-cyclo-6c,9c-epioxido-[1,4]dioxepino[5,6,7-de]quinazoline-6,10c-diol

Conditions
ConditionsYield
(i) TsOH, (ii) Py, (iii) aq. NH3; Multistep reaction;
tetradotoxin
4368-28-9

tetradotoxin

4,9-anhydrotetrodotoxin
13072-89-4

4,9-anhydrotetrodotoxin

Conditions
ConditionsYield
(i) Ac2O, TsOH, (ii) Py, (iii) aq. NH3; Multistep reaction;
tetradotoxin
4368-28-9

tetradotoxin

(5R)-2,4c-diamino-12-hydroxymethyl-(4ac)-1(3),4,4a,5,9,10-hexahydro-5r,9c;7t,10at-dimethano-[1,3]dioxocino[6,5-d]pyrimidine-7,10t,11syn,12syn-tetraol
7724-38-1

(5R)-2,4c-diamino-12-hydroxymethyl-(4ac)-1(3),4,4a,5,9,10-hexahydro-5r,9c;7t,10at-dimethano-[1,3]dioxocino[6,5-d]pyrimidine-7,10t,11syn,12syn-tetraol

Conditions
ConditionsYield
(i) Ac2O, TsOH, (ii) Py, (iii) aq. NH3; Multistep reaction;
tetradotoxin
4368-28-9

tetradotoxin

(7S)-2-amino-4c,5t,10t,11anti-tetrahydroxy-(4ac)-1(3),4,4a,5-tetrahydro-7r,10ac-methano-oxocino[4,5-d]pyrimidine-6,9-dione
6548-69-2

(7S)-2-amino-4c,5t,10t,11anti-tetrahydroxy-(4ac)-1(3),4,4a,5-tetrahydro-7r,10ac-methano-oxocino[4,5-d]pyrimidine-6,9-dione

Conditions
ConditionsYield
With sulfuric acid; periodic acid at 0℃;

Tetrodotoxin Chemical Properties

MF: C11H17N3O8
MW: 319.27
EINECS: 224-458-8
Product Categories: Living creature toxin;Sodium channel
Mol File: 4368-28-9.mol
storage temp：  2-8°C
solubility：  H2O: stable at pH 4-5 if stored frozensoluble
form：  powder
color：  white
Merck：  13,9318
Synonyms:FUGU POISON;TTX;TETRODOTOXIN;TETRODOTOXIN, FUGU SPECIES;OCTAHYDRO-12-(HYDROXYMETHYL)-2-IMINO-5,9:7,10A-DIMETHANO-10AH-[1,3]DIOXOCINO[6,5-D]PYRIMIDINE-4,7,10,11,12-PENTOL;10abeta,11s*,12s*))-10alph;12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano-10ah-(1,3)dioxocino(6,5-d)pyri;4aalpha,5alpha,7alpha,9alpha,10alpha,10abeta,11s*,12s*))-octahydro-(4r-(4alph
The structure of  FUGU POISON is: 

          

Tetrodotoxin Toxicity Data With Reference

1.   

orl-mus LD50:435 µg/kg

   JJPAAZ    Japanese Journal of Pharmacology. 17 (1967),267.
2.   

ipr-mus LD50:8 µg/kg

   SCIEAS    Science. 144 (1964),1100.
3.   

scu-mus LD50:8 µg/kg

   CTOXAO    Clinical Toxicology. 4 (1971),331.
4.   

ivn-mus LD50:9 µg/kg

   JJPAAZ    Japanese Journal of Pharmacology. 17 (1967),267.

Tetrodotoxin Consensus Reports

FUGU POISON(4368-28-9) is reported in EPA TSCA Inventory.

Tetrodotoxin Safety Profile

Hazard Codes：  T+
Risk Statements：  26/27/28
Safety Statements：  22-36/37/39-45
RIDADR：  UN 3462 6.1/PG 1
WGK Germany：  3
RTECS：  IO1450000
F：  10-18
HazardClass：  6.1(a)
PackingGroup：  I
Poison by ingestion, intraperitoneal, subcutaneous, and intravenous routes. When heated to decomposition it emits toxic fumes of NOx.

Tetrodotoxin Specification

1、Fire Fighting Measures of  FUGU POISON(4368-28-9)
General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear.  Extinguishing Media: Use water spray, dry chemical, carbon dioxide, or chemical foam. 
2、Handling and Storage of  FUGU POISON(4368-28-9)
Handling: Do not breathe dust, vapor, mist, or gas. Do not get in eyes, on skin, or on clothing. Use only in a chemical fume hood. 
Storage: Store in a tightly closed container. Store in a dry area. Poison room locked/refrigerator. 

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