2-hydroxy-3-[11-hydroxy-2-[4-[4-hydroxy-2-[1-hydroxy-3-(3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl)butyl]-3-methylidenespiro[4a,7,8,8a-tetrahydro-4H-pyrano[3,2-b]pyran-6,5'-oxolane]-2'-yl]but-3-en-2-yl]-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-methylpropanoic acid

Base Information

• Chemical Name: 2-hydroxy-3-[11-hydroxy-2-[4-[4-hydroxy-2-[1-hydroxy-3-(3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl)butyl]-3-methylidenespiro[4a,7,8,8a-tetrahydro-4H-pyrano[3,2-b]pyran-6,5'-oxolane]-2'-yl]but-3-en-2-yl]-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-methylpropanoic acid
• CAS No.: 78111-17-8
• Molecular Formula: C44H68 O13
• Molecular Weight: 805.016
• Hs Code.: 29321900
• European Community (EC) Number: 616-589-8
• Wikipedia: Okadaic_acid
• Wikidata: Q105224352
• Mol file: 78111-17-8.mol

Synonyms:halochondrine A;78111-17-8;CCRIS 3329;HSDB 7243;C44-H68-O13;1,7-Dioxaspiro[5.5]undec-10-ene-2-propanoic acid, .alpha.,5-dihydroxy-.alpha.,10-dimethyl-8-[(1R,2E)-1-methyl-3-[(2R,4'aR,5R,6'S,8'R,8'aS)-octahydro-8'-hydroxy-6'-[(1S,3S)-1-hydroxy-3-[(2S,3R,6S)-3-methyl-1,7-dioxaspiro[5.5]undec-2-yl]butyl]-7'-methylenes

Chemical Property of 2-hydroxy-3-[11-hydroxy-2-[4-[4-hydroxy-2-[1-hydroxy-3-(3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl)butyl]-3-methylidenespiro[4a,7,8,8a-tetrahydro-4H-pyrano[3,2-b]pyran-6,5'-oxolane]-2'-yl]but-3-en-2-yl]-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-methylpropanoic acid

Chemical Property:

• Appearance/Colour: white crystals or powder
• Melting Point: 164-166 °C
• Refractive Index: 1.5940 (estimate)
• Boiling Point: 921.6 °C at 760 mmHg
• PKA: 3.87±0.16(Predicted)
• Flash Point: 269.4 °C
• PSA: 182.83000
• Density: 1.28 g/cm³
• LogP: 5.21360
• Storage Temp.: −20°C
• Solubility.: DMSO: ≥1 mg/mL
• Water Solubility.: It is soluble in ethanol (25 mg/ml), DMSO (25 mg/ml), methanol (<1 mg/ml), chloroform, acetone, ethyl acetate, DMF, and dimet
• XLogP3: 3.4
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 13
• Rotatable Bond Count: 10
• Exact Mass: 804.46599222
• Heavy Atom Count: 57
• Complexity: 1520

Purity/Quality:

Extra pure，≥95%（HPLC) ^*data from raw suppliers

Okadaic Acid ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 23/24/25-38
• Safety Statements: 26-36/37-45

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CC1CCC2(CCCCO2)OC1C(C)CC(C3C(=C)C(C4C(O3)CCC5(O4)CCC(O5)C=CC(C)C6CC(=CC7(O6)C(CCC(O7)CC(C)(C(=O)O)O)O)C)O)O
• Description: Marine algal blooms, natural phenomena produced by the overgrowth of microscopic marine algae, have become a public health concern because of their increasing frequency and severity. About 300 phytoplanktonic species are known to have the ability to cause these blooms, and one-fourth of them are able to produce toxins, also called phycotoxins. Shellfish, mainly bivalve mollusks, and fish may accumulate these phycotoxins by direct filtration of the producer algal cells or by feeding on contaminated organisms. Human intoxications caused by phycotoxins occur worldwide through consumption of marine fishery products containing bioaccumulated toxins. According to their toxic effects and chemical properties, phycotoxins are classified into different categories. Diarrheic shellfish poisoning (DSP) toxins are one of the most relevant groups of the phytoplanktonic toxins because its presence produces not only severe economic losses, but also health effects in human consumers. The first registered DSP episode after shellfish consumption occurred in 1961 in The Netherlands. However, no relationship with the phycotoxins was established at that time. It was in 1976 when the association between the frequent occurrence of gastroenteritis and the ingestion of phycotoxin-contaminated shellfish was proved the first time. Since then, a large number of DSP episodes have been documented worldwide. However, this number is believed to be much higher because these episodes are not often well documented for the reason that the acute symptoms are sometimes light and intoxicated people do not always require medical assistance. Okadaic acid (OA) and its analogs, the dinophysistoxins (DTX), are lipophilic marine toxins produced by several phytoplanktonic species and responsible for DSP in humans. OA, the main representative toxin of this group, was first isolated in 1981 from the black sponge Halichondria okadai as well as from H. melanodocia. It is usually accumulated by several marine organisms, mainly bivalve mollusks, by eating phytoplankton containing OA. This toxin is highly distributed all over the world, but is especially abundant in Japan in Europe. OA exposure can represent a severe threat to human health beyond its DSP effects, because it was demonstrated to be a specific inhibitor of several types of serine/threonine protein phosphatases and a tumor promoter in animal carcinogenesis experiments.
• Uses: Okadaic acid is a widely distributed marine toxin produced by several phytoplanktonic species and responsible for diarrheic shellfish poisoning in humans. At the molecular level, Okadaic acid is a pot ent and specific inhibitor of various types of serine/threonine protein phosphatases. Due to this enzymatic inhibition, Okadaic acid was reported to induce numerous alterations in relevant cellular ph ysiological processes, including metabolic pathways such as glucose uptake, lipolysis and glycolysis, heme metabolism and glycogen and protein synthesis. Biochemical tool as tumor promoter and probe of cellular regulation. OA is a natural marine toxin produced by different phytoplanktonic species mainly from the dynoflagellates group. It may pass through the food chain to humans who ingest OAcontaminated organisms. Thus, it does not have any commercial applications in medicine, food, construction, or similar industries. However, because of its well-known ability to selectively inhibit several types of serine/threonine protein phosphatases, it is often used in research as a useful tool for studying cellular processes regulated by reversible phosphorylation of proteins, including control of glycogen metabolism, coordination of the cell cycle and gene expression, and maintenance of cytoskeletal structure.Furthermore, it was reported that other marine toxins, different from OA, can also act as specific protein phosphatase (mainly PP1 and PP2A) inhibitors. They are called OA class tumor promoters and were proved to be able to cause skin, stomach, and liver tumors in animals. This has led some authors to suggest a new concept of tumor promotion: the okadaic acid pathway. In this regard, studies with OA, as well as with other OA class tumor promoters, could deepen the knowledge of the mechanisms of cancer development in humans.

Technology Process of 2-hydroxy-3-[11-hydroxy-2-[4-[4-hydroxy-2-[1-hydroxy-3-(3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl)butyl]-3-methylidenespiro[4a,7,8,8a-tetrahydro-4H-pyrano[3,2-b]pyran-6,5'-oxolane]-2'-yl]but-3-en-2-yl]-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-methylpropanoic acid

There total 67 articles about 2-hydroxy-3-[11-hydroxy-2-[4-[4-hydroxy-2-[1-hydroxy-3-(3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl)butyl]-3-methylidenespiro[4a,7,8,8a-tetrahydro-4H-pyrano[3,2-b]pyran-6,5'-oxolane]-2'-yl]but-3-en-2-yl]-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-methylpropanoic acid 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: 87.0%

tribenzyl okadaic acid (104307-13-3) → okadaic acid (78111-17-8)

Guidance literature:

With ammonia; lithium; In ethanol; at -78 ℃; for 0.5h;

DOI:10.1016/S0040-4020(01)86918-0

Reference yield:

{(S)-1-[(R)-2-(4-Methoxy-benzyloxy)-1-methyl-ethyl]-but-3-ynyloxy}-trimethyl-silane (194038-95-4) → okadaic acid (78111-17-8)

Guidance literature:

Multi-step reaction with 16 steps

1: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, -78 deg C, 40 min

2: imidazole / CH₂Cl₂ / 0.75 h

3: 1.) CuI / 1.) Et₂O, from -78 to -40 deg C, 2.) Et₂O, -78 deg C, 2.5 h

4: p-TsOH*H₂O / benzene / 11 h / Ambient temperature

5: 98 percent / TBAF / tetrahydrofuran

6: 86 percent / Dess-Martin periodinane

7: 1.) LDA / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, -78 deg C, 15 min

8: 1.) NaH

9: n-Bu₃SnH, AIBN / toluene / 2 h / 80 °C

10: 77 percent / aq. Na₂PO₄ buffer, DDQ / CH₂Cl₂; 2-methyl-propan-2-ol / 0.05 h / Irradiation

11: 90 percent / Dess-Marti periodinane, NaHCO₃ / CH₂Cl₂ / 0.5 h / Ambient temperature

12: 1.) LiCl, diisopropylethylamine / 1.) CH₃CN, RT, 10 min, 2.) CH₃CN, RT, 20 h

13: (S)-2-methyl-CBS-oxazaborolidine, BF₃*THF / tetrahydrofuran; toluene / 0.08 h / 0 °C

14: p-TsOH*H₂O / benzene / 2 h / Ambient temperature

15: 100 percent / 1M aq. LiOH / tetrahydrofuran / 48 h / Ambient temperature

16: 69 percent / lithium di-tert-butylbiphenylide / tetrahydrofuran / 0.25 h / -78 °C

With 1H-imidazole; lithium hydroxide; copper(l) iodide; n-butyllithium; boron trifluoride-tetrahydrofuran complex; 2,2'-azobis(isobutyronitrile); lithium di-tert-butylbiphenylide; Na₂PO₄ buffer; tetrabutyl ammonium fluoride; tri-n-butyl-tin hydride; sodium hydride; sodium hydrogencarbonate; Dess-Martin periodane; toluene-4-sulfonic acid; N-ethyl-N,N-diisopropylamine; 2,3-dicyano-5,6-dichloro-p-benzoquinone; lithium chloride; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole; lithium diisopropyl amide; In tetrahydrofuran; dichloromethane; toluene; tert-butyl alcohol; benzene;

DOI:10.1021/ja973286p

Reference yield:

(3R,6S)-3-Benzyloxy-6-(tert-butyl-diphenyl-silanyloxymethyl)-tetrahydro-pyran-2-one (194038-96-5) → okadaic acid (78111-17-8)

Guidance literature:

Multi-step reaction with 16 steps

1: 1.) n-BuLi / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, -78 deg C, 40 min

2: imidazole / CH₂Cl₂ / 0.75 h

3: 1.) CuI / 1.) Et₂O, from -78 to -40 deg C, 2.) Et₂O, -78 deg C, 2.5 h

4: p-TsOH*H₂O / benzene / 11 h / Ambient temperature

5: 98 percent / TBAF / tetrahydrofuran

6: 86 percent / Dess-Martin periodinane

7: 1.) LDA / 1.) THF, hexane, -78 deg C, 20 min, 2.) THF, hexane, -78 deg C, 15 min

8: 1.) NaH

9: n-Bu₃SnH, AIBN / toluene / 2 h / 80 °C

10: 77 percent / aq. Na₂PO₄ buffer, DDQ / CH₂Cl₂; 2-methyl-propan-2-ol / 0.05 h / Irradiation

11: 90 percent / Dess-Marti periodinane, NaHCO₃ / CH₂Cl₂ / 0.5 h / Ambient temperature

12: 1.) LiCl, diisopropylethylamine / 1.) CH₃CN, RT, 10 min, 2.) CH₃CN, RT, 20 h

13: (S)-2-methyl-CBS-oxazaborolidine, BF₃*THF / tetrahydrofuran; toluene / 0.08 h / 0 °C

14: p-TsOH*H₂O / benzene / 2 h / Ambient temperature

15: 100 percent / 1M aq. LiOH / tetrahydrofuran / 48 h / Ambient temperature

16: 69 percent / lithium di-tert-butylbiphenylide / tetrahydrofuran / 0.25 h / -78 °C

With 1H-imidazole; lithium hydroxide; copper(l) iodide; n-butyllithium; boron trifluoride-tetrahydrofuran complex; 2,2'-azobis(isobutyronitrile); lithium di-tert-butylbiphenylide; Na₂PO₄ buffer; tetrabutyl ammonium fluoride; tri-n-butyl-tin hydride; sodium hydride; sodium hydrogencarbonate; Dess-Martin periodane; toluene-4-sulfonic acid; N-ethyl-N,N-diisopropylamine; 2,3-dicyano-5,6-dichloro-p-benzoquinone; lithium chloride; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole; lithium diisopropyl amide; In tetrahydrofuran; dichloromethane; toluene; tert-butyl alcohol; benzene;

DOI:10.1021/ja973286p

upstream raw materials:

tribenzyl okadaic acid

(R)-2-[(R)-2-(4-Methoxy-benzyloxy)-1-methyl-ethyl]-oxirane

(2R,3R)-4-(4-Methoxy-benzyloxy)-3-methyl-butane-1,2-diol

(2R,3R)-3,4-diethylmethylenedioxy-2-methyl-butan-1-ol

Downstream raw materials:

okadanol

okadaic acid methyl ester

methyl 27-deoxy-27-oxookadaate

methyl 7,24-bis-O-(tert-butyldimethylsilyl)-27-deoxy-27-oxookadaate

Refernces

• 1、 Ley, Steven V.,Humphries, Alexander C.,Eick, Holger,Downham, Robert,Ross, Andrew R.,Boyce, Richard J.,Pavey, John B. J.,Pietruszka, Joerg. "Total synthesis of the protein phosphatase inhibitor okadaic acid". . p. 3907 - 3911. Retrieved 2007/10/03.
• 2、 Ichikawa, Yoshiyasu,Isobe, Minoru,Goto, Toshio. "Transformation of a Marine Toxic Polyether, Okadaic Acid". . p. 975 - 982. Retrieved 2007/10/02.