(E,2R,3R,7R,8Z)-8-[(8S,8aS)-8-hydroxy-8-methyl-1,2,3,5,7,8a-hexahydroindolizin-6-ylidene]-4,7-dimethyloct-4-ene-2,3-diol

Base Information

• Chemical Name: (E,2R,3R,7R,8Z)-8-[(8S,8aS)-8-hydroxy-8-methyl-1,2,3,5,7,8a-hexahydroindolizin-6-ylidene]-4,7-dimethyloct-4-ene-2,3-diol
• CAS No.: 67016-65-3
• Molecular Formula: C19H33NO3
• Molecular Weight: 323.474
• ChEMBL ID: CHEMBL141991
• DSSTox Substance ID: DTXSID801046308
• Wikidata: Q105302616
• Mol file: 67016-65-3.mol

Synonyms:CHEMBL141991;DTXSID801046308

Chemical Property of (E,2R,3R,7R,8Z)-8-[(8S,8aS)-8-hydroxy-8-methyl-1,2,3,5,7,8a-hexahydroindolizin-6-ylidene]-4,7-dimethyloct-4-ene-2,3-diol

Chemical Property:

• Vapor Pressure: 2.7E-11mmHg at 25°C
• Boiling Point: 481.5°C at 760 mmHg
• PKA: 14.50±0.20(Predicted)
• Flash Point: 234.8°C
• PSA: 63.93000
• Density: 1.1g/cm³
• LogP: 2.18400
• XLogP3: 1.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 5
• Exact Mass: 323.24604391
• Heavy Atom Count: 23
• Complexity: 473

Purity/Quality:

PUMILIOTOXIN B 95.00% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(CC=C(C)C(C(C)O)O)C=C1CC(C2CCCN2C1)(C)O
• Isomeric SMILES: C[C@H](C/C=C(\C)/[C@H]([C@@H](C)O)O)/C=C\1/C[C@]([C@@H]2CCCN2C1)(C)O

Technology Process of (E,2R,3R,7R,8Z)-8-[(8S,8aS)-8-hydroxy-8-methyl-1,2,3,5,7,8a-hexahydroindolizin-6-ylidene]-4,7-dimethyloct-4-ene-2,3-diol

There total 55 articles about (E,2R,3R,7R,8Z)-8-[(8S,8aS)-8-hydroxy-8-methyl-1,2,3,5,7,8a-hexahydroindolizin-6-ylidene]-4,7-dimethyloct-4-ene-2,3-diol 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: 89.0%

(E)-(2R,3R,7R)-8-[(8S,8aS)-8-Hydroxy-8-methyl-hexahydro-indolizin-(6E)-ylidene]-8-iodo-4,7-dimethyl-oct-4-ene-2,3-diol (182053-20-9) → Pumiliotoxin B (67016-65-3)

Guidance literature:

With tert.-butyl lithium; In tetrahydrofuran; pentane; at -78 ℃; for 0.25h;

DOI:10.1021/ja961641q

Reference yield: 70.0%

(6Z,8S,8aS)-8-methyl-6-{(2R,4E)-2-methyl-5-[(4R,5R)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-4-hexenylidene}octahydro-8-indolizinol (119269-59-9) → Pumiliotoxin B (67016-65-3)

Guidance literature:

With hydrogenchloride; In tetrahydrofuran; at 20 ℃; for 0.5h;

DOI:10.1021/jo0200466

Reference yield:

(R)-2-((tert-butyldiphenylsilyl)oxy)-4-(triphenylphosphoranylidene)-3-pentanone (90246-35-8) → Pumiliotoxin B (67016-65-3)

Guidance literature:

Multi-step reaction with 9 steps

1: 97 percent / CH₂Cl₂ / 48 h / Heating

2: 98 percent / iBu₃Al / pentane; toluene / 1 h / Ambient temperature

3: 100 percent / tetrabutylammonium fluoride / tetrahydrofuran / 2 h / Ambient temperature

4: 84 percent / TsOH / acetone / 30 h / Ambient temperature

5: 94 percent / nBuLi / tetrahydrofuran; hexane / 1.5 h / -78 °C

6: 1.) nBuLi, 2.) Et₂AlCl

7: 77 percent / aq. Ba(OH)2 / dioxane / 14 h / 100 °C

8: 68 percent / aq. NaI, pyridinium p-toluenesulfonate / 2 h / 105 °C

9: 89 percent / tBuLi / tetrahydrofuran; pentane / 0.25 h / -78 °C

With barium dihydroxide; n-butyllithium; tetrabutyl ammonium fluoride; tert.-butyl lithium; triisobutylaluminum; diethylaluminium chloride; pyridinium p-toluenesulfonate; toluene-4-sulfonic acid; sodium iodide; In tetrahydrofuran; 1,4-dioxane; hexane; dichloromethane; acetone; toluene; pentane;

DOI:10.1021/ja961641q

upstream raw materials:

(8S,8aS)-8-hydroxy-8-methyl-6(Z)-<6-oxo-2(R),5-dimethyl-7(R)-(tert-butyldiphenylsiloxy)-4(E)-octenylidene>octahydroindolizidine

(E)-(2R,3R,7R)-8-[(8S,8aS)-8-Hydroxy-8-methyl-hexahydro-indolizin-(6E)-ylidene]-8-iodo-4,7-dimethyl-oct-4-ene-2,3-diol

(6Z,8S,8aS)-8-methyl-6-{(2R,4E)-2-methyl-5-[(4R,5R)-2,2,5-trimethyl-1,3-dioxolan-4-yl]-4-hexenylidene}octahydro-8-indolizinol

(3S,4R)-3,4-(isopropylidenedioxy)-2-propanone

Refernces

Efficient total syntheses of pumiliotoxins A and B. Applications of iodide-promoted iminium ion-alkyne cyclizations in alkaloid construction

10.1021/ja961641q

The research focuses on the efficient total syntheses of pumiliotoxins A and B, which are alkaloids with significant pharmacological activities derived from amphibians, specifically certain brightly colored frogs native to the rain forests of western Colombia and Panama. The study aims to improve upon previous synthetic routes to these important alkaloids, providing a more practical and efficient method for their production. The central step in the synthesis involves the formation of the piperidine ring and the establishment of the (Z)-alkylidene side chain through an iodide-promoted iminium ion-alkyne cyclization. Key chemicals used in the process include alkynes, epoxides, N-[(benzyloxy)carbonyl]-L-proline, and various reagents for the cyclization and purification steps. The conclusions of the research highlight the substantial improvement over previous synthetic methods, with the total synthesis of (+)-15(S)-pumiliotoxin A achieved in 5 steps with a 32% overall yield, and (+)-pumiliotoxin B achieved in four steps with a 44% overall yield. These syntheses not only provide a more accessible route to these alkaloids but also offer a platform for the production of gram quantities of these toxins and their congeners, which are valuable research tools in pharmacology and potential models for the development of new myotonic or cardiotonic agents.