474-25-9

Basic information

• Product Name: Chenodeoxycholic acid
• Synonyms: (R)-4-((3R,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid;(R)-4-((3R,5S,7R,10S,13R)-3,7-dihydroxy-10,13-dimethyl-hexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid;URSODEOXYCHOLOC ACID,3,7-dihydroxy-,(3-alpha,5-beta,7-alpha)-cholan-24-oicaci;5β-Cholanic acid-3α,7α-diol Chenodiol;URSODEOXYCHOLOC ACID;3,7-dihydroxy-,(3-alpha,5-beta,7-alpha)-cholan-24-oicaci;3,7-dihydroxy-,(3alpha,5beta,7alpha)-cholan-24-oicaci;3,7-Dihydroxy-5-Cholanicacid
• CAS NO: 474-25-9
• Molecular Formula: C24H40O4
• Molecular Weight: 392.57
• EINECS: 207-481-8
• Product Categories: Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Intracellular receptor
• Mol File: 474-25-9.mol

Chemical Properties

• Melting Point: 165-167 °C(lit.)
• Boiling Point: 437.26°C (rough estimate)
• Flash Point: 9℃
• Appearance: White to off-white/Powder
• Density: 0.9985 (rough estimate)
• Refractive Index: 1.4460 (estimate)
• Storage Temp.: Refrigerator
• Solubility: PRACTICALLY INSOLUBLE
• PKA: pKa 4.34 (Uncertain)
• Water Solubility: PRACTICALLY INSOLUBLE
• Merck: 13,2062
• BRN: 3219887
• CAS DataBase Reference: Chenodeoxycholic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Chenodeoxycholic acid(474-25-9)
• EPA Substance Registry System: Chenodeoxycholic acid(474-25-9)

Safety Data

• Hazard Codes: Xn
• Statements: 63
• Safety Statements: 22-24/25-45-36/37
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 2
• RTECS: FZ1980000
• Hazardous Substances Data: 474-25-9(Hazardous Substances Data)

Usage

Uses

Used in Medical Therapy:
Chenodeoxycholic acid is used as a therapeutic agent for dissolving gallstones. It reduces the biliary concentration of cholesterol relative to that of bile acids and phospholipid, reducing the saturation and thus the lithogenicity of the bile. Success rates in dissolving gallstones are in the range of 50-70% within 4-24 months of treatment.
Used in Treatment of Cerebrotendinous Xanthomatosis (CTX):
Chenodeoxycholic acid is used as a long-term replacement therapy for CTX, a rare genetic disorder that affects the nervous system and causes the accumulation of cholesterol in various tissues.
Used in Investigation of Small-Intestinal Absorption:
Chenodeoxycholic acid has been used in a study to investigate its effects on the small-intestinal absorption of bile acids in patients with ileostomies.
Used in Apoptosis Induction:
Chenodeoxycholic acid is used as an apoptosis inducer via protein kinase C (PKC)-dependent signaling pathways. It is a major bile acid in many vertebrates, occurring as the N-glycine and/or N-taurine conjugate.
Used in Solubilization and Transport of Dietary Lipids:
Chenodeoxycholic acid, along with other bile acids, forms mixed micelles with lecithin in bile, which solubilize cholesterol and facilitate its excretion. It also facilitates fat absorption in the small intestine by micellar solubilization of fatty acids and monoglycerides.
Used in Dye Solar Cells:
Chenodeoxycholic acid is used as a staining additive, commonly used with ruthenium or organic photo-sensitizers in the preparation of staining solutions for dye solar cells. This co-adsorbent prevents dye aggregation on the semiconductor surface, reducing losses in the solar cell's operation.
Used in Supramolecular Chemistry:
Chenodeoxycholic acid acts as a urea receptor in supramolecular chemistry, which can contain anions.
Used in Treatment of Constipation:
Chenodeoxycholic acid is used to treat constipation and cerebrotendineous xanthomatosis.
Used in Regulation of Genes Involved in Lipid Metabolism:
Chenodeoxycholic acid is a physiological ligand for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism. Bile acid-controlled signaling pathways are promising novel targets to treat metabolic diseases such as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.
Chemical Properties:
Chenodeoxycholic acid is an off-white solid and is available under the brand name CHEWM.

Originator

Rowell (USA)

History

Chenodeoxycholic acid was isolated in 1924 from goose gall by Adolf Windaus and human gall by Heinrich Wieland.Its complete structural configuation was elucidated by Hans Lettre at the University of Gottingen. In 1968, William Admirand and Donald Small at Boston University Medical School established that in patients with gallstones their bile was saturated with cholesterol, sometimes even exhibiting microcrystals, whereas this was not the case in normal people.It was then found that biliary levels of cholic acid and chenodeoxycholic acid were lower in patients with cholesterol gallstones than in normal people. Leslie Thistle and John Schoenfield at the Mayo Clinic in Rochester, Minnesota, then administered individual bile salts by mouth for four months and found that chenodeoxycholic acid reduced the amount of cholesterol in the bile.This led to a national collaborative study in the United States, which confirmed the effectiveness of chenodeoxycholic acid in bringing about dissolution of gallstones in selected patients. However, recent developments such as laparoscopic cholecystectomy and endoscopic biliary techniques have curtailed the role of chenodeoxycholic acid and ursodeoxycholic acid in the treatment of cholelithiasis.

Manufacturing Process

To 1,400 ml of an approximately 50% water/triglycol solution of the potassium salt of chenodeoxycholic acid, obtained by the Wolff-Kishner reduction (using hydrazine hydrate and potassium hydroxide) from 50 g of 7- acetyl-12-ketochenodeoxycholic acid, 220 ml of dilute hydrochloric acid is added to bring the pH to 2. The solution is stirred and the crude chenodeoxycholic acid precipitates. The precipitate is recovered and dried to constant weight at about 60°C. About 36 g of the crude chenodeoxycholic acid, melting in the range of 126°-129°C, is obtained. 25 g of crude chenodeoxycholic acid so obtained is dissolved in 750 ml of acetonitrile while stirring and heating. 3 g of activated charcoal is added and then removed by suction filtering. The resulting liquid filtrate is cooled, the pure chenodeoxycholic acid crystallizing out. The crystals are recovered by suction filtering and the recovered crystals dried under vacuum. The yield is 19 g of pure chenodeoxycholic acid with a melting range of 168°-171°C.

Therapeutic Function

Gallostone dissolving agent

World Health Organization (WHO)

Chenodeoxycholic acid was introduced in 1975 for the treatment of cholelithiasis. It is available in several countries and the World Health Organization is not aware that registration has been refused in any other country.

Flammability and Explosibility

Nonflammable

Purification Methods

This major bile acid in vertebrates (~80mg) is chromatographed on silica gel (5g) and eluted with CHCl3/EtOAc (3:2) and crystallised from EtOAc/hexane. It has IR: max 1705 cm-1(CHCl3). It also crystallises from EtOAc, EtOAc/heptane after purifying via the poorly soluble Na and K salt if necessary. [Kametani et al. J Org Chem 4 7 2331 1982, Beilstein 10 IV 1604.]

InChI:InChI=1/C24H40O5/c1-13(4-7-21(28)29)16-5-6-17-22-18(12-20(27)24(16,17)3)23(2)9-8-15(25)10-14(23)11-19(22)26/h13-20,22,25-27H,4-12H2,1-3H3,(H,28,29)/t13-,14+,15-,16-,17+,18+,19-,20+,22?,23+,24-/m1/s1

Synthetic route

3α,7α-Dihydroxy-chol-11-ensaeure → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With palladium on activated charcoal; hydrogen In methanol at 70℃; under 30003 Torr; for 12h;	99%

(4R)-methyl 4-((3R,5R,7R,10S,13R,17R)-3-acetoxy-7-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate (19684-68-5) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With water; sodium hydroxide In methanol for 1h; Reflux;	97%
With water; sodium hydroxide In methanol; water for 2h; Reagent/catalyst; Reflux;	97%
With sodium hydroxide In tetrahydrofuran; methanol; water at 70℃; for 3h;	95%

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

Conditions	Yield
Stage #1: 7-Ketolithocholic acid With potassium tert-butylate; palladium(II) hydroxide; potassium hydroxide In isopropyl alcohol at 20℃; for 0.166667h; Stage #2: With hydrogen In isopropyl alcohol at 40 - 80℃; Reagent/catalyst; Temperature;	A n/a B 95%
With sodium tetrahydroborate; sodium hydrogencarbonate In water at 20℃; for 0.5h; var. reducing agents;	A 94% B 2%
With potassium In tert-butyl alcohol for 0.5h; Heating; var. reducing agents;	A 6% B 94%

7-Ketolithocholic acid (4651-67-6) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With sodium tetrahydroborate In methanol at 0℃; for 2h;	93%

(4R)-methyl 4-((3R,5S,7R,10S,13R,17R)-7-acetoxy-3-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate (93701-16-7) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With water; sodium hydroxide In methanol for 6h; Reflux;	90.9%

3α,7α-dihydroxy-12-oxo-5β-cholan-24-oic acid (2458-08-4) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With potassium hydroxide; hydrazine In 2-methoxy-ethanol; water at 110 - 135℃; for 12h; Wolff-Kishner reduction;	90%
With potassium hydroxide; ethylene glycol weiteres Reagens: N2H4;
With potassium hydroxide; 2,2'-[1,2-ethanediylbis(oxy)]bisethanol weiteres Reagens: N2H4;

methyl 3α,7α-diacetoxy-5β-cholan-24-oate (2616-71-9) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
Stage #1: methyl 3α,7α-diacetoxy-5β-cholan-24-oate With sodium hydroxide In dichloromethane at 20 - 30℃; for 1h; Stage #2: With sulfuric acid	87.8%
In methanol; isopropyl alcohol reflux 4 h then RT;	69%
With potassium hydroxide

methyl 3α,7α-diacetoxy-12-one-5β-cholest-24-carboxylate (28535-81-1) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With hydrazine hydrate; potassium hydroxide In ethylene glycol at 120 - 210℃; for 5h;	86.6%
With sodium ethanolate; hydrazine hydrate at 160℃;
With hydrazine hydrate; potassium hydroxide In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol at 120 - 210℃; for 4h; Wolff-Kishner Reduction; Large scale;
Stage #1: methyl 3α,7α-diacetoxy-12-one-5β-cholest-24-carboxylate With hydrazine hydrate; potassium hydroxide In 2,2'-[1,2-ethanediylbis(oxy)]bisethanol at 120℃; for 2h; Stage #2: at 210℃; for 3h;
Multi-step reaction with 2 steps 1: Alkaline conditions View Scheme

ethyl 3α-benzoyloxy-7α-hydroxy-chol-5-en-24-oate → chenodeoxycholic acid (474-25-9)

Conditions	Yield
Stage #1: ethyl 3α-benzoyloxy-7α-hydroxy-chol-5-en-24-oate With palladium 10% on activated carbon; hydrogen; acetic acid In ethanol under 2844.39 Torr; for 24h; Stage #2: With methanol; sodium hydroxide for 18h; Reflux;	82%

C29H48O5 → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With water; sodium hydroxide In methanol at 80℃; for 4h;	30%

ethyl chenodeoxycholate acid 7-acetate → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With water; sodium hydroxide In methanol at 75℃; for 6h;	28%

C29H46O5 → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With water; sodium hydroxide In methanol at 75℃; for 5h;	28%

C33H48O5 → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With water; sodium hydroxide In methanol at 60℃; for 8h;	26%

3,7-diketocholanic acid (859-97-2) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With ethanol; platinum Hydrogenation;
With acetic acid; platinum Hydrogenation;
With sodium tetrahydroborate; water; sodium hydroxide

3,7-diketocholanic acid (859-97-2) → chenodeoxycholic acid (474-25-9) + ursodeoxycholic acid (128-13-2)

Conditions	Yield
With aluminum isopropoxide; isopropyl alcohol

7-Ketolithocholic acid (4651-67-6) + sodium ethanolate (141-52-6) → chenodeoxycholic acid (474-25-9) + ursodeoxycholic acid (128-13-2)

Conditions	Yield
at 200℃;

methyl 3α-hydroxy-7α-acetoxy-12-oxocholanate (71837-87-1) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With potassium hydroxide; ethylene glycol weiteres Reagens: N2H4;
With potassium hydroxide; 2,2'-[1,2-ethanediylbis(oxy)]bisethanol weiteres Reagens: N2H4;

3,7-diketocholanic acid (859-97-2) + aluminum isopropoxide (555-31-7) + isopropyl alcohol (67-63-0) → chenodeoxycholic acid (474-25-9) + ursodeoxycholic acid (128-13-2)

3α,7α-dihydroxy-12-oxocholanic acid tosylhydrazone (79580-95-3) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With sodium tetrahydroborate In acetic acid for 3h; Ambient temperature;

7-hydroxy-3-(sulfooxy)-(3α,5β,7α)-cholan-24-oic acid (64520-49-6, 68780-68-7, 68780-73-4, 68833-02-3, 124815-69-6, 59132-32-0) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With hydrogenchloride In methanol; acetone at 37℃; for 18h; Product distribution; solvolyse methods, var. of temp., solvent, reagent and time;

chenodeoxycholic acid 7-sulfate (59132-31-9) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With hydrogenchloride; 2,2-dimethoxy-propane In methanol; ethyl acetate at 25℃; for 24h; Product distribution; solvolyse methods, var. of temp., solvent, reagent and time;

3α,7α-dihydroxy-5β-cholan-24-oic acid 3-β-D-glucuronide → D-glucuronic acid (6556-12-3, 489-91-8, 528-16-5, 552-12-5, 577-46-8, 643-33-4, 2240-07-5, 6294-16-2, 10133-02-5, 18402-78-3, 18968-14-4, 21179-08-8, 23018-83-9, 33599-45-0, 33599-46-1, 46171-67-9, 46171-69-1, 46172-26-3, 70021-34-0, 71031-08-8, 104195-06-4, 106499-29-0, 124817-72-7) + chenodeoxycholic acid (474-25-9)

Conditions	Yield
With acetate buffer; glycyrrhizinic acid hydrolase at 45℃; hydrolysis; other enzyme (β-glucuronidase);

(25RS)-3α,7α-dihydroxy-5β-cholestan-26-oic acid (17974-66-2) → chenodeoxycholic acid (474-25-9)

Conditions	Yield
rat liver homogenate, NAD, pH=8.5;

3α,7α,24-trihydroxy-5β-cholestan-26-oic acid → chenodeoxycholic acid (474-25-9)

Conditions	Yield
rat liver homogenate, NAD, pH=8.5;

(E)-(R)-6-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-Dihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-2-methyl-hept-2-enoic acid → chenodeoxycholic acid (474-25-9)

Conditions	Yield
rat liver homogenate, NAD, pH=8.5;

6A,6C-bis(2-naphthylsulfonyl)-γ-cyclodextrin chenodeoxycholic acid 1:1 complex → chenodeoxycholic acid (474-25-9) + 6A,6C-bis(2-naphthylsulfonyl)-γ-cyclodextrin

Conditions	Yield
In water; ethylene glycol at 25℃; Equilibrium constant; decomplexation;

6A,6D-bis(2-naphthylsulfonyl)-γ-cyclodextrin chenodeoxycholic acid 1:1 complex → chenodeoxycholic acid (474-25-9) + 6A,6D-bis(2-naphthylsulfonyl)-γ-cyclodextrin

Conditions	Yield
In water; ethylene glycol at 25℃; Equilibrium constant; decomplexation;

6A,6E-bis(2-naphthylsulfonyl)-γ-cyclodextrin chenodeoxycholic acid 1:1 complex → chenodeoxycholic acid (474-25-9) + 6A,6E-bis(2-naphthylsulfonyl)-γ-cyclodextrin

Conditions	Yield
In water; ethylene glycol at 25℃; Equilibrium constant; decomplexation;

3α,7α-diacetoxy-12-oxo-5β-cholan-24-oic acid methyl ester → chenodeoxycholic acid (474-25-9)

Conditions	Yield
With potassium hydroxide; ethylene glycol weiteres Reagens: N2H4;
With potassium hydroxide; 2,2'-[1,2-ethanediylbis(oxy)]bisethanol weiteres Reagens: N2H4;

methanol (67-56-1) + chenodeoxycholic acid (474-25-9) → chenodeoxycholic acid methyl ester (3057-04-3)

Conditions	Yield
With thionyl chloride	100%
With toluene-4-sulfonic acid at 20℃; for 1h;	100%
With toluene-4-sulfonic acid for 2h; Reflux; Inert atmosphere;	100%

chenodeoxycholic acid (474-25-9) → Dehydrochenodeoxycholic acid (4185-00-6)

Conditions	Yield
With dipotassium hydrogenphosphate; D-glucose; Pseudomonas paucimobilis; yeast extracxt; peptone In water at 28℃; for 24h;	100%

chenodeoxycholic acid (474-25-9) + diazomethyl-trimethyl-silane (18107-18-1) → chenodeoxycholic acid methyl ester (3057-04-3)

Conditions	Yield
In methanol; hexane; toluene at 20℃;	100%

N-Methyltaurine (107-68-6) + chenodeoxycholic acid (474-25-9) → 3α,7α-dihydroxy-5β-cholan-24-oyl-N-methyltaurine (93790-68-2)

Conditions	Yield
With triethylamine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride In N,N-dimethyl-formamide at 20℃; for 1h;	100%

methanol (67-56-1) + chenodeoxycholic acid (474-25-9) → C26H44O4

Conditions	Yield
	100%

chenodeoxycholic acid (474-25-9) + acetic anhydride (108-24-7) → 3α,7α-diacetoxy-24-phenyl-5β-cholan-24-oic acid (33628-52-3)

Conditions	Yield
With pyridine at 20℃; for 24h;	99%
With pyridine at 20℃; for 3h;	97%
With pyridine at 20℃; for 15h;	95%

ethanol (64-17-5) + chenodeoxycholic acid (474-25-9) → ethyl 3α,7α-dihydroxy-5β-cholan-24-oate

Conditions	Yield
With Candida antarctica lipase B In hexane at 55℃; for 24h; Reagent/catalyst; Solvent; Temperature; Time; Enzymatic reaction;	99%
With heterologous Rhizopus oryzae lipase immobilized on Octadecyl Sepabeads In di-isopropyl ether at 55℃; Enzymatic reaction;	87%

bis(4-methoxyphenyl)amine (101-70-2) + chenodeoxycholic acid (474-25-9) → (3R,5S,7R,8R,9S,10S,13R,14S,17R)-17-((R)-4-(bis(4-methoxyphenyl)amino)butan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol

Conditions	Yield
With 9-(2-chlorophenyl)acridine; di-tert-butyl peroxide; copper(II) hexafluoroacetylacetonate In ethyl acetate at 35℃; for 24h; Inert atmosphere; Irradiation;	99%

chenodeoxycholic acid (474-25-9) → 7-Ketolithocholic acid (4651-67-6)

Conditions	Yield
With dimethyl sulfoxide; triethylamine; trifluoroacetic anhydride In dichloromethane at -30℃; for 1.5h; Temperature; Swern Oxidation;	98.6%
With sodium bromate; sulfuric acid; sodium bromide In dichloromethane at 20 - 30℃; for 6h;	96.1%
With N-Bromosuccinimide In water; acetone at 20℃; for 2h; Darkness;	94%

formic acid (64-18-6) + chenodeoxycholic acid (474-25-9) → 3α,7α-diformyloxy-5β-cholan-24-oic acid (6159-50-8, 6058-15-7)

Conditions	Yield
With perchloric acid In tetrahydrofuran at 50℃; for 15h;	98%
With perchloric acid In tetrahydrofuran; water at 54℃; Inert atmosphere;	96%
at 55℃; for 20h;	95%

chenodeoxycholic acid (474-25-9) + 2,2,2,-trichloroethoxycarbonyl azide → 2,2,2-trichloroethyl ((3R)-3-((3R,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)butyl)carbamate

Conditions	Yield
With dmap; copper diacetate In acetonitrile at 80℃; for 0.166667h; Schlenk technique; Sealed tube;	98%

chenodeoxycholic acid (474-25-9) + ethylene diamine mono-p-toluenesulfonic acid salt (14034-59-4) → 23-(4,5-dihydroimidazol-2-yl)-24-nor-5β-cholan-3α,7α-diol

Conditions	Yield
at 220 - 225℃; for 0.75h;	97%

chenodeoxycholic acid (474-25-9) + glycine ethyl ester hydrochloride (5680-79-5) → [(R)-4-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-Dihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-acetic acid methyl ester (69320-16-7)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide	97%

chenodeoxycholic acid (474-25-9) → 3,7-diketocholanic acid (859-97-2)

Conditions	Yield
With sodium bromate; ammonium cerium (IV) nitrate In water; acetonitrile at 80℃; Green chemistry;	96%
With potassium bromate; phosphoric acid; potassium bromide In tetrahydrofuran; water; acetonitrile at 20℃; for 3h; Reagent/catalyst; Solvent; Temperature;	90.6%
With aluminium(III) chloride hexahydrate; potassium peroxymonosulfate In water at 50℃; for 0.166667h; Microwave irradiation;	83%
With chromium(VI) oxide; acetic acid

chenodeoxycholic acid (474-25-9) + (2-(3)H(N))taurine → C26H44(3)HNO6S

Conditions	Yield
With hydrogenchloride; tributyl-amine; chloroformic acid ethyl ester In 1,4-dioxane for 0.25h; Ambient temperature;	95%

chenodeoxycholic acid (474-25-9) + (1,2-(14)C)taurine → C24(14)C2H45NO6S

Conditions	Yield
With hydrogenchloride; tributyl-amine; chloroformic acid ethyl ester In 1,4-dioxane for 0.25h; Ambient temperature;	95%

chenodeoxycholic acid (474-25-9) → ferric chenodeoxycholate

Conditions	Yield
With iron(III) chloride; sodium hydroxide In water at 35℃; pH=8;	95%

chenodeoxycholic acid (474-25-9) + tri-Boc-spermine (114459-62-0) → N1-(3α,7α-dihydroxy-5β-cholan-24-carbonyl)-(N4,N9N12-tri-tert-butoxycarbonyl)-1,12-diamino-4,9-diazadodecane (287964-36-7)

Conditions	Yield
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 25℃; for 24h; Acylation;	93%

Tau (107-35-7) + chenodeoxycholic acid (474-25-9) → sodium taurochenodeoxycholate (6009-98-9)

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; sodium hydroxide In water; acetonitrile; tert-butyl alcohol at 20 - 80℃;	93%

chenodeoxycholic acid (474-25-9) + benzyl bromide (100-39-0) → benzyl 3α,7α-dihydroxy-5β-cholan-24-oate (111992-94-0)

Conditions	Yield
With caesium carbonate In acetonitrile Reflux;	92%
With caesium carbonate In acetonitrile for 4h; Reflux;	80%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 55℃;
With caesium carbonate In acetonitrile Reflux;

TMSCH2N2 + chenodeoxycholic acid (474-25-9) → methyl (5β,7α)-12-hydroxy-3-oxo-cholan-24-oate (14773-00-3)

Conditions	Yield
In methanol; diethyl ether; toluene at 20℃; for 0.333333h;	91%

1-methyl-piperazine (109-01-3) + chenodeoxycholic acid (474-25-9) → N1<(3α,5β,7α)3,7-dihydroxy-24-oxo-cholan-24-yl>N4methyl-piperazine (86678-67-3)

Conditions	Yield
With tributyl-amine; chloroformic acid ethyl ester In 1,4-dioxane 10 deg C, 10 min then rt., 1 h;	90%

chenodeoxycholic acid (474-25-9) + methylamine (74-89-5) → N methyl(3α,5β,7α)3,7-dihydroxy-cholan-24-amide (86678-62-8)

Conditions	Yield
With tributyl-amine; chloroformic acid ethyl ester In 1,4-dioxane 10 deg C, 10 min then rt., 1 h;	90%
With tributyl-amine; chloroformic acid ethyl ester Multistep reaction;

chenodeoxycholic acid (474-25-9) + benzylamine (100-46-9) → N benzyl (3α,5β,7α)3,7-dihydroxy-cholan-24-amide (86678-64-0)

Conditions	Yield
With tributyl-amine; chloroformic acid ethyl ester In 1,4-dioxane 10 deg C, 10 min then rt., 1 h;	90%
With ammonium hydroxide; tributyl-amine; chloroformic acid ethyl ester Multistep reaction;

Upstream product

• 859-97-2 3,7-diketocholanic acid 
• 71837-87-1 methyl 3α-hydroxy-7α-acetoxy-12-oxocholanate 
• 2616-71-9 methyl 3α,7α-diacetoxy-5β-cholan-24-oate 
• 555-31-7 aluminum isopropoxide 
• 67-63-0 isopropyl alcohol 
• 33628-52-3 (-)-3α,7α-diacetoxy-5β-cholanoic acid 
• 2616-71-9 Methyl Chenodeoxycholate Diacetate 
• 6533-77-3 4-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-Diacetoxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoic acid 
• 17974-66-2 (25RS)-3α,7α-dihydroxy-5β-cholestan-26-oic acid 
• 64-17-5 ethanol 
• 4651-67-6 7-Ketolithocholic acid 
• 64-19-7 acetic acid 
• 7647-01-0 hydrogenchloride 
• 16564-43-5 glycochenodeoxycholic acid sodium salt 

Downstream Products

• 3862-26-8 5β-cholestane-3α,7α-diol 
• 4651-67-6 7-Ketolithocholic acid 
• 640-79-9 glycochenodeoxycholate 
• 516-35-8 taurochenodeoxycholic acid 
• 6159-50-8 3α,7α-diformyloxy-5β-cholan-24-oic acid 
• 91612-92-9 4-nitrophenyl chenodeoxycholate 
• 65384-76-1 N-(phenyl)-3α,7α-dihydroxy-5β-cholan-24-amide 
• 4185-00-6 Dehydrochenodeoxycholic acid 
• 14772-95-3 7α-hydroxy-3-oxochol-4-en-24-oic acid 
• 64520-49-6 7-hydroxy-3-(sulfooxy)-(3α,5β,7α)-cholan-24-oic acid 
• 92054-20-1 5β-cholanic acid-3α,7α-diol di-p-fluorobenzoate 
• 88165-77-9 bis(3α-phenylsulfonyloxy-5β-cholansaeure-7α-yl)diester 
• 86678-64-0 N benzyl (3α,5β,7α)3,7-dihydroxy-cholan-24-amide 
• 23848-46-6 CDC-OH 

Relevant articles and documents

Non-stereospecific formation of 3α,7α,24-trihydroxy-5β-cholestan-26- oic acid during chenodeoxycholic acid biosynthesis

Incubation of 3α,7α-dihydroxy-5β-cholestan-26-oic acid and its Δ24- analog with rat liver homogenate produced a mixture of C-24,25 diastereoisomers of 3α,7α,24-trihydroxy-5β-cholestan-26-oic acid, a key intermediate of chenodeoxycholic acid biosynthesis.

Engineering Regioselectivity of a P450 Monooxygenase Enables the Synthesis of Ursodeoxycholic Acid via 7β-Hydroxylation of Lithocholic Acid

We engineered the cytochrome P450 monooxygenase CYP107D1 (OleP) from Streptomyces antibioticus for the stereo- and regioselective 7β-hydroxylation of lithocholic acid (LCA) to yield ursodeoxycholic acid (UDCA). OleP was previously shown to hydroxylate testosterone at the 7β-position but LCA is exclusively hydroxylated at the 6β-position, forming murideoxycholic acid (MDCA). Structural and 3DM analysis, and molecular docking were used to identify amino acid residues F84, S240, and V291 as specificity-determining residues. Alanine scanning identified S240A as a UDCA-producing variant. A synthetic “small but smart” library based on these positions was screened using a colorimetric assay for UDCA. We identified a nearly perfectly regio- and stereoselective triple mutant (F84Q/S240A/V291G) that produces 10-fold higher levels of UDCA than the S240A variant. This biocatalyst opens up new possibilities for the environmentally friendly synthesis of UDCA from the biological waste product LCA.

Method for synthesizing 3alpha, 7alpha-dihydroxy-5-beta-cholanic acid from duck cholic acid

The invention belongs to the field of organic synthesis of carbocyclic compounds, and particularly relates to a method for synthesizing 3alpha, 7alpha-dihydroxy-5-beta-cholanic acid from duck cholic acid. According to the method, chenodeoxycholic acid with purity of 97.6% is synthesized by using duck cholic acid as a raw material. The comprehensive yield is 87.8%, the purity of the product is highwhile a high-temperature reaction is avoided, and later impurity removal is simple and convenient.

Preparation method of chenodeoxycholic acid

The invention belongs to the field of organic synthesis, and provides a preparation method of chenodeoxycholic acid, which comprises the following steps of: extracting chenodeoxycholic acid serving as one of main components in waste after chenodeoxycholic acid is extracted from duck gall paste, namely seal cholic acid, serving as a raw material; and the chenodeoxycholic acid is obtained by a propylidene protection method, acetylation, propylidene removal, methyl esterification, reaction with p-toluenesulfonyl chloride, bromine substitution, debromination, deprotection and the like. The method for preparing chenodeoxycholic acid is simple, the raw material source is rich, the product yield is high, and industrialization is easy to realize.

Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids via Hydrogen Atom Transfer

The oxidation of primary alcohols and aldehydes to the corresponding carboxylic acids is a fundamental reaction in organic synthesis. In this paper, we report a new chemoselective process for the oxidation of primary alcohols and aldehydes. This metal-free reaction features a new oxidant, an easy to handle procedure, high isolated yields, and good to excellent functional group tolerance even in the presence of vulnerable secondary alcohols and tert-butanesulfinamides.

Decarbonated cholesteric aldehyde as well as preparation method and application thereof

The invention provides decarbonated cholesteric aldehyde as well as a preparation method and application thereof. The decarbonated cholesteric aldehyde is a compound as shown in a formula (I), or a salt thereof, or a stereoisomer thereof. R1 and R2 are respectively and independently selected from hydrogen, C1-C6 alkyl, halogen, hydroxyl, carboxyl, aldehyde group, amino or nitro. The decarbonated cholesteric aldehyde has good antibacterial activity, especially has a good inhibition effect on clostridium difficile, and can be used for preparing drugs for inhibiting clostridium difficile. Meanwhile, carbon-loss chenodeoxycholic acid, carbon-loss cholesteric alcohol and chenodeoxycholic acid can be prepared by taking the carbon-loss cholesteric aldehyde as an initial raw material, and the yield is high and is superior to that in the prior art. Besides, the invention provides a preparation method of various decarbonated cholesteric aldehyde, the preparation method is high in yield and purity, the raw material duck cholic acid used in the preparation method is wide in source and low in cost, an industrial method for utilizing industrial waste duck cholic acid is developed, and the industrialization of the preparation method is more feasible.

Synthetic method of chenodeoxycholic acid

The invention belongs to the field of organic synthesis, and provides a synthesis method of chenodeoxycholic acid, which comprises the following steps: by using seal cholic acid which is one of the main components in the waste after chenodeoxycholic acid is extracted from duck gall paste as a raw material, carrying out methyl esterification, reacting with p-toluenesulfonyl chloride, carrying out bromine substitution, debromination, deprotection and the like to obtain chenodeoxycholic acid. The method for preparing chenodeoxycholic acid is simple, the raw material source is rich, the product yield is high, and industrialization is easy to realize.

Preparation method and application of seal cholic acid

The invention provides a method for selectively separating seal cholic acid from a duck bile extract, which facilitates the utilization of the seal cholic acid which is an important biological resource in the duck bile. The invention also provides a method for preparing chenodeoxycholic acid from the seal cholic acid. Therefore, the problem of insufficient supply of chenodeoxycholic acid raw materials can be alleviated, improved. and meanwhile, corresponding biological waste pollution is also avoided. The method is easy for industrial production and has very good economic value and applicationprospect.

Method for preparing chenodeoxycholic acid from seal cholic acid

The invention provides a method for preparing chenodeoxycholic acid CDCA by taking seal cholic acid as a raw material, on one hand, an application is found for seal cholic acid, and on the other hand,a new raw material source is provided for chenodeoxycholic acid, so that the problem of supply shortage of chenodeoxycholic acid crude drugs can be partially relieved, meanwhile, the problem of corresponding biological waste pollution is avoided, the problem of industrial production is well solved, and the method has very good economic value and application prospect.

Preparation method of chenodeoxycholic acid

The invention relates to the technical field of medicine synthesis, in particular to a preparation method of chenodeoxycholic acid. The invention develops a method for synthesizing the chenodeoxycholic acid by taking hyodeoxycholic acid(3alpha, 6alpha-dihydroxy-5beta-cholanic acid)as a raw material through nine steps of reaction, the reaction conditions of each step are mild, the control is easy,the process is simple, the used raw materials are wide in source, low in price and easy to obtain, the yield is high, the total yield can reach 61%, the synthesis cost is low, and the method is suitable for mass preparation and industrial production.