Pharmakon1600-01500605

Base Information

• Chemical Name: Pharmakon1600-01500605
• CAS No.: 128-13-2
• Molecular Formula: C24H40O4
• Molecular Weight: 392.579
• Hs Code.: 29181990
• NSC Number: 757382
• Mol file: 128-13-2.mol

Synonyms:SR-05000001965;Spectrum_000636;Spectrum2_000947;Spectrum3_000574;Spectrum4_000373;Spectrum5_001551;BSPBio_001988;KBioGR_000865;KBioSS_001116;DivK1c_000416;SCHEMBL288251;SPECTRUM1500605;SPBio_000914;HMS501E18;KBio1_000416;KBio2_001116;KBio2_003684;KBio2_006252;KBio3_001488;NINDS_000416;HMS1921I19;HMS2092C10;Pharmakon1600-01500605;CCG-40274;NSC757382;NSC-757382;SDCCGMLS-0066577.P001;IDI1_000416;NCGC00178876-01;SBI-0051553.P002;AB00052124_03;SR-05000001965-1;SR-05000001965-2

Chemical Property of Pharmakon1600-01500605

Chemical Property:

• Appearance/Colour: white crystalline powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 203-204 °C(lit.)
• Refractive Index: 60.5 ° (C=2, EtOH)
• Boiling Point: 547.1 °C at 760 mmHg
• PKA: pKa 5.04±0.04(H2O t = 25.0±0.1 I = 0.00)(Approximate)
• Flash Point: 298.8 °C
• PSA: 77.76000
• Density: 1.128 g/cm³
• LogP: 4.47790
• Storage Temp.: Refrigerator
• Solubility.: ethanol: 50 mg/mL, clear
• Water Solubility.: practically insoluble
• XLogP3: 4.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 392.29265975
• Heavy Atom Count: 28
• Complexity: 605

Purity/Quality:

99% ^*data from raw suppliers

Ursodeoxycholic acid ^*data from reagent suppliers

Safty Information:

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

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(CCC(=O)O)C1CCC2C1(CCC3C2C(CC4C3(CCC(C4)O)C)O)C
• Isomeric SMILES: C[C@H](CCC(=O)O)[C@H]1CCC2[C@@]1(CCC3C2[C@H](C[C@H]4[C@@]3(CC[C@H](C4)O)C)O)C
• Drug Interactions: (1) In combination with chenodeoxycholic acid, the effect of promoting cholesterol level and de-saturation in bile were more than single drugs. The effect is also greater than that of the sum of the two drugs. (2) This product is not suitable taken together with cholestyramine or antacids containing aluminum hydroxide for not affecting the absorption. (3) Oral contraceptives may affect the efficacy of the product.
• Uses: Ursodeoxycholic acid is a naturally occurring bile salt in humans. It is rapidly absorbed in the small intestine and excreted with the bile. Ursodeoxycholic acid is the drug of choise for the treatment of primary biliary cirrhosis and primary sclerosis cholanyitis. The daily dose amounts to 10-15 mg/kg. It has no side effects even after a treatment period of up to 20 years.Dissolution of gallstones. Mainly used for the treatment of inoperable cholesterol gallstones, it will have a cure rate especially in the case when gallbladder is basically normal, stones have a 15mm or lower diameters, X-ray penetrable, non-calcified and high-floating cholesterol stones.Ursodeoxycholic acid can also improve the efficacy of α-interferon on treatment of chronic hepatitis C. It can also used to treat diarrhea, rare constipation, allergic reactions, itching, headache, dizziness, stomach pain, pancreatitis and bradycardia Patients of completely biliary obstruction or severe liver dysfunction and pregnant women should avoid using. Ursodeoxycholic acid (UDCS) is a cell protectant used extensively to mitigate hepatic and biliary diseases. Ursodeoxycholic acid may be used to study its specific activities that range from reduction of cholesterol absorpition, cholesterol gallstone dissolution to suppression of immune response. It is also used as an anticholelithogenic. Epimer with Chenodiol with respect to the hydroxyl group at C7.
• Production method: Method 1: Use chenodeoxycholic acid as raw materials Preparation of 3α, 7α-diacetyl cholic acid methyl ester; Take 36ml of anhydrous methanol, and pass through 1g dried hydrogen chloride gas, add bile acid 12g, stir, heat and reflux for 20-30min. After standing for several hours at room temperature when crystals are separated out, freeze, filter, wash with ether, and dry to obtain methyl cholate. Take 2g methyl cholate, add 9.6 mL of benzene, 2.4mL pyridine, 2.4 mL of acetic anhydride, shake for 10-15min, stand for 20h at room temperature, then pour the reaction mixture into 100ml of water, remove the benzene layer, repeatedly wash with distilled water before recycling the solvents. Wash the solid residue with petroleum ether once, and re-crystallize with methanol-aqueous solution to obtain 3α, 7α-diacetyl bile acid methyl ester. Bile acid methyl → → 3α, 7α-diacetyl bile acid methyl ester Preparation of Chenodeoxycholic acid: Take the 1.5 g diacetyl bile acid methyl ester, add 24 mL acetic acid, add potassium chromate solution (Take 0.76g potassium chromate to dissolve it in 1.8ml take in water), heated to 40 °C, perform reaction for 8h, add water 120ml, shaking for some moment, placed 12h, filter, wash with distilled water till neutralization, dry to give 3α, 7α-diacetoxy-12-keto bile acid methyl ester, referred briefly as the 12-ketone. Take 12-15 g 12-ketone, add 150 mL 2-glycol ether, 15 mL 80% hydrazine hydrate solution, and 15 g potassium hydroxide. Heat to 30 °C and reflux for 15h, heat to 195-200 °C, refluxed for 2.5h, heat to 217 °C for some moment of reaction cool to 190 °C, add 0.7ml hydrazine hydrate solution, heat from within 215 °C to 220 °C within 3h, cool, add 600mL distilled water, adjust to pH 3 with 10% sulfuric acid, separate out the crystals, filter, wash with water until neutralization. Add ethyl acetate, dump the aqueous layer, use water to wash the organic layer was washed for 1-2 times, vacuum distillation and obtain 3α, 7α-dihydroxy cholanic acid, namely Chenodeoxycholic acid. 3α, 7α-diacetyl methyl cholate → 3α, 7α-diacetoxy-12-Keto ursodeoxycholic acid methyl ester → 3α, 7α-dihydroxy ursodeoxycholic acid (Chenodeoxycholic acid) Preparation of refined ursodeoxycholic acid; Taken 2 g chenodeoxycholic acid, add 100ml of acetic acid and 20g potassium acetate, shake to dissolve. Add potassium chromate 1.5g (dissolved in 10 mL of water), at room temperature overnight, add water 200ml, separate out the crystals, filter, wash, and dry to obtain 3α-hydroxy-7-keto-ursodeoxycholic acid. Take 4g 3α-hydroxy-7-keto-ursodeoxycholic acid, add 100 mL n-butanol, heat to about 115 °C, gradually add 8 g metal sodium after which, white slurry gradually comes out, keep reaction for 30min, add 120ml water, stir and heat to transparently dissolve. Evaporate the organic layer under reduced pressure; add 500 mL water to the residue, dissolve, and filter. Adjust the pH the filtrate to pH 3 with 10% sulfuric acid which will yield white precipitate, filter, wash till neutralization with water, dry, wash with ethyl acetate, crystallize with diluted ethanol and obtain 3α, 7β-dihydroxycholanic acid, that’s refined ursodeoxycholic acid. Chenodeoxycholic acid [potassium chromate] → 3α-hydroxy-7-keto acid [sodium metal, 115 °C] → 3α, 7β-Keto ursodeoxycholic acid methyl ester (Ursodeoxycholic acid) Method 2: Use pig bile or bile salts as raw material; Use thin layer chromatography to isolate ursodeoxycholic acid from pigs bile or bile salt. Pig bile salt contains free and bound type of UDCA whose content is about 30%; pig bile contains bound UDCA whose content is about 0.6%.
• Therapeutic Function: Gallostone dissolving agent, Hepatoprotectant
• Clinical Use: Dissolution of gallstonesUrsodeoxycholic acid or ursodiol is a naturally occurring bile acid that is used dissolve cholesterol gall stones and to treat cholestatic forms of liver diseases including primary biliary cirrhosis.
• Drug interactions: Potentially hazardous interactions with other drugs Ciclosporin: unpredictably increases the absorption of ciclosporin in some patients.

Technology Process of Pharmakon1600-01500605

There total 115 articles about Pharmakon1600-01500605 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: 98.0%

7-Ketolithocholic acid (4651-67-6) → ursodeoxycholic acid (128-13-2)

Guidance literature:

With glucose dehydrogenase; D-Glucose; NADPH; 7β-hydroxysteroid dehydrogenase; In aq. phosphate buffer; at 30 ℃; for 1h; pH=8; Concentration; pH-value; Enzymatic reaction;

DOI:10.1016/j.procbio.2014.12.026

Reference yield: 96.0%

C24H36O4 → ursodeoxycholic acid (128-13-2)

Guidance literature:

C₂₄H₃₆O₄; With potassium tert-butylate; In tert-butyl alcohol; for 0.5h;

With palladium 10% on activated carbon; hydrogen; In tert-butyl alcohol; at 80 ℃; for 12h; under 3750.38 Torr; Solvent; Reagent/catalyst; Temperature;

Reference yield: 95.0%

7-Ketolithocholic acid (4651-67-6) → chenodeoxycholic acid (474-25-9) + ursodeoxycholic acid (128-13-2)

Guidance literature:

7-Ketolithocholic acid; With potassium tert-butylate; palladium(II) hydroxide; potassium hydroxide; In isopropyl alcohol; at 20 ℃; for 0.166667h;

With hydrogen; In isopropyl alcohol; at 40 - 80 ℃; Reagent/catalyst; Temperature;

upstream raw materials:

3,7-diketocholanic acid

7-Ketolithocholic acid

sodium ethanolate

aluminum isopropoxide

Downstream raw materials:

bis(3α-phenylsulfonyloxy-5β-cholansaeure-7α-yl)diester

3α,7β-dihydroxy-5β-cholan-24-oic acid methyl ester

ethyl 3α,7β-dihydroxy-23-(phenylseleno)-5β-cholan-24-oate

homo-ursodeoxycholic acid

Refernces

• 1、 Hamada, Fumio,Minato, Shingo,Osa, Tetsuo,Ueno, Akihiko. "Fluorescent Sensors for Molecules Guest-Responsive Monomer and Excimer Fluorescence of 6A,6B-; 6A,6C-; 6A,6D-; and 6A,6E-Bis(2-naphthylsulfonyl)-γ-cyclodextrins". . p. 1339 - 1346. Retrieved 1997.
• 2、 Giovannini, Pier Paolo,Grandini, Alessandro,Perrone, Daniela,Pedrini, Paola,Fantin, Giancarlo,Fogagnolo, Marco. "7α- and 12α-Hydroxysteroid dehydrogenases from Acinetobacter calcoaceticus lwoffii: a new integrated chemo-enzymatic route to ursodeoxycholic acid". . p. 1385 - 1390. Retrieved 2008.
• 3、 Chen, Wang,Hu, Daihua,Feng, Zili,Liu, Zhaopeng. "An effective synthesis of ursodeoxycholic acid from dehydroepiandrosterone". . . Retrieved 2021.
• 4、 Zheng, Ming-Min,Wang, Ru-Feng,Li, Chun-Xiu,Xu, Jian-He. "Two-step enzymatic synthesis of ursodeoxycholic acid with a new 7β-hydroxysteroid dehydrogenase from Ruminococcus torques". . p. 598 - 604. Retrieved 2015.
• 5、 Kollerov,Monti,Deshcherevskaya,Lobastova,Ferrandi,Larovere,Gulevskaya,Riva,Donova. "Hydroxylation of lithocholic acid by selected actinobacteria and filamentous fungi". . p. 370 - 378. Retrieved 2013.
• 6、 Zheng, Ming-Min,Chen, Fei-Fei,Li, Hao,Li, Chun-Xiu,Xu, Jian-He. "Continuous Production of Ursodeoxycholic Acid by Using Two Cascade Reactors with Co-immobilized Enzymes". . p. 347 - 353. Retrieved 2018.
• 7、 Chen, Xi,Cui, Yunfeng,Feng, Jinhui,Wang, Yu,Liu, Xiangtao,Wu, Qiaqing,Zhu, Dunming,Ma, Yanhe. "Flavin Oxidoreductase-Mediated Regeneration of Nicotinamide Adenine Dinucleotide with Dioxygen and Catalytic Amount of Flavin Mononucleotide for One-Pot Multi-Enzymatic Preparation of Ursodeoxycholic Acid". . p. 2497 - 2504. Retrieved 2019.
• 8、 Castaldi, Graziano,Perdoncin, Giulio,Giordano, Claudio. "STEREOCHEMISTRY OF REDUCTION OF CYCLIC KETONES BY ALKALI METALS AND BY SODIUM DITHIONITE.". . p. 2487 - 2490. Retrieved 1983.
• 9、 -. "Preparation method of ursodeoxycholic acid". Paragraph 0024-0027. . Retrieved 2020/06/24.