505-75-9

Usage

Uses

1. Used in Research Applications:
Cicutoxin is used as a research tool for studying the effects of neurotoxins on the central nervous system. Its potent action on the nervous system makes it a valuable compound for understanding the mechanisms of neurotoxicity and developing potential treatments for related conditions.
2. Used in Toxicological Studies:
Cicutoxin is used in toxicological studies to investigate the effects of poisoning and to develop methods for detecting and mitigating the risks associated with exposure to this deadly toxin. This research is crucial for public health and safety, as well as for the development of antidotes and treatments for poisoning incidents.
3. Used in Educational Purposes:
Cicutoxin is used as a case study in educational settings to teach students about the dangers of toxic plants and the importance of proper identification and avoidance. It serves as a cautionary example of the potential consequences of ingesting poisonous substances and the need for vigilance in the natural environment.
4. Used in Forensic Investigations:
Cicutoxin is used in forensic investigations to identify cases of poisoning, particularly in instances where water hemlock ingestion is suspected. Its unique chemical properties and the specific symptoms associated with its ingestion can help investigators determine the cause of death and potentially identify the source of the toxin.
5. Used in Ethnobotanical Studies:
Cicutoxin is used in ethnobotanical studies to explore the historical and cultural significance of water hemlock and its role in traditional medicine and folklore. Understanding the uses and perceptions of this plant can provide insights into the relationship between humans and the natural world, as well as the potential risks and benefits associated with the use of toxic plants in traditional practices.

InChI:InChI=1/C17H22O2/c1-2-14-17(19)15-12-10-8-6-4-3-5-7-9-11-13-16-18/h4,6,8,10,12,15,17-19H,2,11,13-14,16H2,1H3/b6-4+,10-8+,15-12+

Synthetic route

(4R,5E,7E,9E)‐17‐((tetrahydro‐2H‐pyran‐2‐yl)oxy)heptadeca‐5,7,9‐trien‐11,13‐diyn‐4‐ol (1150616-77-5) → Cicutotoxin (505-75-9)

Conditions	Yield
With toluene-4-sulfonic acid In methanol at 20℃; for 0.5h; Inert atmosphere;	61%
With toluene-4-sulfonic acid In methanol at 20℃; for 1.5h; Darkness;	53%

7-bromohepta-4,6-diyn-1-ol (1001587-76-3) + (4R,5E,7E,9E)-10-(tributylstannyl)deca-5,7,9-trien-4-ol (1265526-17-7) → Cicutotoxin (505-75-9)

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; potassium fluoride; copper(l) iodide; triphenyl-arsane; 2,6-di-tert-butyl-4-methyl-phenol In 1-methyl-pyrrolidin-2-one at 45℃; for 3.5h; Stille coupling; Inert atmosphere;

7-iodohepta-4,6-diyn-1-ol (1265526-19-9) + (4R,5E,7E,9E)-10-(tributylstannyl)deca-5,7,9-trien-4-ol (1265526-17-7) → Cicutotoxin (505-75-9)

Conditions	Yield
With tris(dibenzylideneacetone)dipalladium(0) chloroform complex; copper(l) iodide; triphenyl-arsane; 2,6-di-tert-butyl-4-methyl-phenol In tetrahydrofuran at 20 - 45℃; for 5h; Stille coupling; Inert atmosphere;

pent-1-yn-5-ol (5390-04-5) → Cicutotoxin (505-75-9)

Conditions

Yield

Multi-step reaction with 4 steps 1: iodine; potassium hydroxide / methanol; water / 7 h / 20 °C 2: piperidine; copper(l) chloride / 1 h / 0 °C / Inert atmosphere; Neat (no solvent) 3: N-Bromosuccinimide; silver nitrate / acetone / 18 h / 20 °C / Inert atmosphere; Darkness 4: copper(l) iodide; potassium fluoride; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; triphenyl-arsane; 2,6-di-tert-butyl-4-methyl-phenol / 1-methyl-pyrrolidin-2-one / 3.5 h / 45 °C / Inert atmosphere View Scheme

7-(trimethylsilyl)hepta-4,6-diyn-1-ol (83670-22-8) → Cicutotoxin (505-75-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; silver nitrate / acetone / 18 h / 20 °C / Inert atmosphere; Darkness 2: copper(l) iodide; potassium fluoride; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; triphenyl-arsane; 2,6-di-tert-butyl-4-methyl-phenol / 1-methyl-pyrrolidin-2-one / 3.5 h / 45 °C / Inert atmosphere View Scheme

5-iodo-4-pentyn-1-ol (94230-39-4) → Cicutotoxin (505-75-9)

Conditions

Yield

Multi-step reaction with 3 steps 1: piperidine; copper(l) chloride / 1 h / 0 °C / Inert atmosphere; Neat (no solvent) 2: N-Bromosuccinimide; silver nitrate / acetone / 18 h / 20 °C / Inert atmosphere; Darkness 3: copper(l) iodide; potassium fluoride; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; triphenyl-arsane; 2,6-di-tert-butyl-4-methyl-phenol / 1-methyl-pyrrolidin-2-one / 3.5 h / 45 °C / Inert atmosphere View Scheme

(E)-7-chlorohept-6-en-4-yn-1-ol (646534-13-6) → Cicutotoxin (505-75-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 3 h / -20 °C / Inert atmosphere 1.2: 0.5 h / Inert atmosphere 2.1: copper(l) iodide; tris(dibenzylideneacetone)dipalladium(0) chloroform complex; triphenyl-arsane; 2,6-di-tert-butyl-4-methyl-phenol / tetrahydrofuran / 5 h / 20 - 45 °C / Inert atmosphere View Scheme

(5E,7E,9E)‐17‐((tetrahydro‐2H‐pyran‐2‐yl)oxy)heptadeca‐5,7,9‐trien‐11,13‐diyn‐4‐one → Cicutotoxin (505-75-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: dimethylsulfide borane complex; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 1.5 h / -50 °C 2: toluene-4-sulfonic acid / methanol / 1.5 h / 20 °C / Darkness View Scheme

C17H20O4 → Cicutotoxin (505-75-9)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: 12 h / 20 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 0.5 h / 20 °C / Schlenk technique 2.2: 12 h 3.1: diisobutylaluminium hydride / dichloromethane / 1.5 h / -78 °C / Darkness; Schlenk technique 4.1: barium(II) hydroxide / tetrahydrofuran; water / 0.5 h / 20 °C / Schlenk technique; Darkness 5.1: dimethylsulfide borane complex; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 1.5 h / -50 °C 6.1: toluene-4-sulfonic acid / methanol / 1.5 h / 20 °C / Darkness View Scheme

C17H20O3 → Cicutotoxin (505-75-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: barium(II) hydroxide / tetrahydrofuran; water / 0.5 h / 20 °C / Schlenk technique; Darkness 2: dimethylsulfide borane complex; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 1.5 h / -50 °C 3: toluene-4-sulfonic acid / methanol / 1.5 h / 20 °C / Darkness View Scheme

2‐(hepta‐4,6‐diyn‐1‐yloxy)tetrahydro‐2H‐pyran (159646-46-5) → Cicutotoxin (505-75-9)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: methyllithium / tetrahydrofuran; diethyl ether / 0.5 h / Schlenk technique 1.2: 1 h / -78 °C 1.3: 4 h / -78 - 20 °C 2.1: 12 h / 20 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 0.5 h / 20 °C / Schlenk technique 3.2: 12 h 4.1: diisobutylaluminium hydride / dichloromethane / 1.5 h / -78 °C / Darkness; Schlenk technique 5.1: barium(II) hydroxide / tetrahydrofuran; water / 0.5 h / 20 °C / Schlenk technique; Darkness 6.1: dimethylsulfide borane complex; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 1.5 h / -50 °C 7.1: toluene-4-sulfonic acid / methanol / 1.5 h / 20 °C / Darkness View Scheme

(2E,4E)‐12‐((tetrahydro‐2H‐pyran‐2‐yl) oxy)dodeca‐2,4‐dien‐6,8‐diynoic acid → Cicutotoxin (505-75-9)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 0.5 h / 20 °C / Schlenk technique 1.2: 12 h 2.1: diisobutylaluminium hydride / dichloromethane / 1.5 h / -78 °C / Darkness; Schlenk technique 3.1: barium(II) hydroxide / tetrahydrofuran; water / 0.5 h / 20 °C / Schlenk technique; Darkness 4.1: dimethylsulfide borane complex; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 1.5 h / -50 °C 5.1: toluene-4-sulfonic acid / methanol / 1.5 h / 20 °C / Darkness View Scheme

(2E,4E)‐N‐methoxy‐N‐methyl‐12-((tetrahydro‐2H‐pyran‐2‐yl)oxy)dodeca‐2,4‐dien‐6,8‐diyne amide → Cicutotoxin (505-75-9)

Conditions

Yield

Multi-step reaction with 4 steps 1: diisobutylaluminium hydride / dichloromethane / 1.5 h / -78 °C / Darkness; Schlenk technique 2: barium(II) hydroxide / tetrahydrofuran; water / 0.5 h / 20 °C / Schlenk technique; Darkness 3: dimethylsulfide borane complex; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran / 1.5 h / -50 °C 4: toluene-4-sulfonic acid / methanol / 1.5 h / 20 °C / Darkness View Scheme

tert-butyldimethylsilyl chloride (18162-48-6) + Cicutotoxin (505-75-9) → (5E,7E,9E)-(R)-17-(tert-Butyl-dimethyl-silanyloxy)-heptadeca-5,7,9-triene-11,13-diyn-4-ol

Conditions	Yield
With dmap; triethylamine In dichloromethane at 0℃; for 3h; Substitution;	80%

(S)-(+)-2-methoxy-2-trifluoromethyl-2-phenylacetyl chloride (39637-99-5, 20445-33-4) + Cicutotoxin (505-75-9) → (R)-3,3,3-Trifluoro-2-methoxy-2-phenyl-propionic acid (2E,4E,6E)-(R)-1-propyl-14-((R)-3,3,3-trifluoro-2-methoxy-2-phenyl-propionyloxy)-tetradeca-2,4,6-triene-8,10-diynyl ester

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 5h; Esterification;	76%

acetic anhydride (108-24-7) + Cicutotoxin (505-75-9) → Acetic acid (8E,10E,12E)-(R)-14-hydroxy-heptadeca-8,10,12-triene-4,6-diynyl ester + Acetic acid (2E,4E,6E)-(R)-14-acetoxy-1-propyl-tetradeca-2,4,6-triene-8,10-diynyl ester + Acetic acid (2E,4E,6E)-(R)-14-hydroxy-1-propyl-tetradeca-2,4,6-triene-8,10-diynyl ester

Conditions	Yield
With pyridine at 0℃; for 8.3h;	A 55% B 23% C 10%

Cicutotoxin (505-75-9) + methyl iodide (74-88-4) → (8E,10E,12E)-(R)-1,14-Dimethoxy-heptadeca-8,10,12-triene-4,6-diyne + (14R)-(8E,10E,12E)-14-methoxyheptadecatriene-4,6-diyn-1-ol + (5E,7E,9E)-(R)-17-Methoxy-heptadeca-5,7,9-triene-11,13-diyn-4-ol

Conditions	Yield
With potassium hydroxide In N,N-dimethyl-formamide at 0℃; for 0.166667h;	A 27% B 5% C 24%

Cicutotoxin (505-75-9) → 17-hydroxy-heptadeca-5t,7t,9t-triene-11,13-diyn-4-one (25525-18-2) + (8E,10E,12E)-14-oxoheptadecatriene-4,6-diyn-1-al + (8E,10E,12E)-(R)-14-Hydroxy-heptadeca-8,10,12-triene-4,6-diynal (321655-32-7)

Conditions	Yield
With pyridine-SO3 complex; dimethyl sulfoxide; triethylamine In dichloromethane at 0℃; for 4h;	A 8% B 16% C 13%

(R)-methoxytrifluoromethylphenylacetyl chloride (20445-33-4, 39637-99-5) + Cicutotoxin (505-75-9) → (S)-3,3,3-Trifluoro-2-methoxy-2-phenyl-propionic acid (2E,4E,6E)-(R)-1-propyl-14-((S)-3,3,3-trifluoro-2-methoxy-2-phenyl-propionyloxy)-tetradeca-2,4,6-triene-8,10-diynyl ester

Conditions	Yield
With dmap; triethylamine In dichloromethane at 20℃; for 5h; Esterification;

Cicutotoxin (505-75-9) → (8E,10E,12E)-(R)-14-Hydroxy-heptadeca-8,10,12-triene-4,6-diynoic acid (321655-37-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 13 percent / DMSO; SO3*pyridine; Et3N / CH2Cl2 / 4 h / 0 °C 2: 71 percent / KOH; I2 / 0.25 h / 0 °C 3: 75 percent / 1 N aq. NaOH / methanol / 9 h / 20 °C View Scheme

Cicutotoxin (505-75-9) → (8E,10E,12E)-(R)-14-Hydroxy-heptadeca-8,10,12-triene-4,6-diynoic acid methyl ester (321655-36-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 13 percent / DMSO; SO3*pyridine; Et3N / CH2Cl2 / 4 h / 0 °C 2: 71 percent / KOH; I2 / 0.25 h / 0 °C View Scheme

Cicutotoxin (505-75-9) → (8E,10E,12E)-(R)-14-Hydroxy-heptadeca-8,10,12-triene-4,6-diynoic acid amide

Conditions	Yield
Multi-step reaction with 4 steps 1: 13 percent / DMSO; SO3*pyridine; Et3N / CH2Cl2 / 4 h / 0 °C 2: 71 percent / KOH; I2 / 0.25 h / 0 °C 3: 75 percent / 1 N aq. NaOH / methanol / 9 h / 20 °C 4: 63 percent / NH4Cl; DPPA; Et3N / dimethylformamide / 8.5 h / 0 °C View Scheme

Cicutotoxin (505-75-9) → (8E,10E,12E)-(R)-14-Hydroxy-heptadeca-8,10,12-triene-4,6-diynoic acid butylamide

Conditions	Yield
Multi-step reaction with 4 steps 1: 13 percent / DMSO; SO3*pyridine; Et3N / CH2Cl2 / 4 h / 0 °C 2: 71 percent / KOH; I2 / 0.25 h / 0 °C 3: 75 percent / 1 N aq. NaOH / methanol / 9 h / 20 °C 4: 70 percent / DPPA; Et3N / dimethylformamide / 9.5 h / 0 °C View Scheme

Cicutotoxin (505-75-9) → 4-Methoxy-benzoic acid (2E,4E,6E)-(R)-14-(tert-butyl-dimethyl-silanyloxy)-1-propyl-tetradeca-2,4,6-triene-8,10-diynyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / Et3N, DMAP / CH2Cl2 / 3 h / 0 °C 2: 94 percent / Et3N, DMAP / CH2Cl2 / 3 h / 0 °C View Scheme

Upstream product

• 25462-05-9 deca-2t,4t,6t-trienal 
• 159646-46-5 2‐(hepta‐4,6‐diyn‐1‐yloxy)tetrahydro‐2H‐pyran 
• 1150616-80-0 (5E,7E,9E)‐17‐((tetrahydro‐2H‐pyran‐2‐yl)oxy)heptadeca‐5,7,9‐trien‐11,13‐diyn‐4‐ol 
• 1150616-77-5 (4R,5E,7E,9E)‐17‐((tetrahydro‐2H‐pyran‐2‐yl)oxy)heptadeca‐5,7,9‐trien‐11,13‐diyn‐4‐ol 
• 1001587-76-3 7-bromohepta-4,6-diyn-1-ol 
• 1265526-17-7 (4R,5E,7E,9E)-10-(tributylstannyl)deca-5,7,9-trien-4-ol 
• 1265526-19-9 7-iodohepta-4,6-diyn-1-ol 
• 5390-04-5 pent-1-yn-5-ol 
• 83670-22-8 7-(trimethylsilyl)hepta-4,6-diyn-1-ol 
• 94230-39-4 5-iodo-4-pentyn-1-ol 
• 646534-13-6 (E)-7-chlorohept-6-en-4-yn-1-ol 
• 6728-26-3 (E)-2-Hexenal 

Relevant academic research and scientific papers

A concise synthesis of R-(-)-cicutoxin, a natural 17-carbon polyenyne

A concise synthesis of the natural polyenyne R-(-)-cicutoxin (1) is described. After several trials, the successful synthesis commenced with three key fragments, R-(-)-1-hexyn-3-ol (8), 1,4-diiodo-1,3-butadiene (9), and THP-protected 4,6-heptadiyn-1-ol (6

Expeditious synthesis of polyacetylenic water hemlock toxins and their effects on the major GABAA receptor isoform

Classical synthetic approaches to highly unsaturated polyene/yne natural products rely on iterative cross-coupling of linear fragments. Herein, we present an expeditious and unified approach to the unsaturated backbone of polyacetylenes via domino cuprate addition/4π-electrocyclic ring opening of a stereodefined cyclobutene intermediate. This sets the stage for a detailed biological assessment of the role of Virol A and Cicutoxin as inhibitors of GABA induced chloride currents, providing further insight into the interaction of these highly potent toxins towards the GABAA receptor, including the structure-activity relationship of the derivatives.

Sn/Li exchange reactions in 1,ω-distannylated conjugated trienes and tetraenes: An enabling step for polyene synthesis

Successive treatments of (1E,3E,5E)- or (1E,3Z,5E)-1,6-bis(tributylstannyl) hexa-1,3,5-triene with nBuLi and butanal rendered polyenyl alcohols resulting from one Sn/Li exchange reaction and exhibiting complete retention of the configuration of all C=C bonds. Mono- or dimethylated all-E-configured 1,6-distannylated conjugated trienes as well as all-E-1,8-bis(tributylstannyl) octa-1,3,5,7-tetraene and dimethylated congeners thereof reacted similarly. The respective Sn/Li exchange reactions affected the substructure Bu 3Sn-CH=CH with a 93-94:7-6 preference over Bu3Sn-CMe=CH and with a 90:10 preference over Bu3Sn-CH=CMe. all-E-1-Lithio-6- (tributylstannyl)hexa-1,3,5-triene was incorporated into navenone B after Negishi coupling and into (-)-cicutoxin after acylation. NMR spectroscopy of our navenone B specimen revealed that certain resonances were misassigned previously. Molecular tinkertoy: all-E-1,6-(Tributylstannyl)hexa-1,3,5-triene, all-E-1,8-(tributylstannyl)octa-1,3,5,7-tetraene, and related bis(tributylstannylated) polyenes undergomono-Sn/Li exchange reactions. They set the stage for terminus-differentiating functionalizations, which provide inter alianavenone B and (-)-cicutoxin.