434-13-9

Basic information

• Product Name: LITHOCHOLIC ACID
• Synonyms: 3-HYDROXYCHOLANIC ACID;3ALPHA-HYDROXYCHOLANIC ACID;3ALPHA-HYDROXY-5BETA-CHOLANIC ACID;3ALPHA-HYDROXY-5BETA-CHOLAN-24-OIC ACID;5BETA-CHOLAN-24-OIC ACID-3A-OL;5BETA-CHOLAN-24-OIC ACID-3ALPHA-OL;5BETA-CHOLANIC ACID-3ALPHA-OL;LITHOCHOLIC ACID
• CAS NO: 434-13-9
• Molecular Formula: C24H40O3
• Molecular Weight: 376.57
• EINECS: 207-099-1
• Product Categories: Steroids;Bile Acids;Biochemistry;Intermediates & Fine Chemicals;Pharmaceuticals;Inhibitors
• Mol File: 434-13-9.mol

Chemical Properties

• Melting Point: 183-188 °C(lit.)
• Boiling Point: 445.09°C (rough estimate)
• Flash Point: 9℃
• Appearance: White to off-white/Powder
• Density: 1.0454 (rough estimate)
• Vapor Pressure: 1.4E-12mmHg at 25°C
• Refractive Index: 35.5 ° (C=1, EtOH)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Dichloromethane (Slightly, Heated), DMSO (Slightly, Heate
• PKA: 4.76±0.10(Predicted)
• Water Solubility: 18.83ug/L(25 oC)
• Merck: 5545
• BRN: 3217757
• CAS DataBase Reference: LITHOCHOLIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: LITHOCHOLIC ACID(434-13-9)
• EPA Substance Registry System: LITHOCHOLIC ACID(434-13-9)

Safety Data

• Safety Statements: 22-24/25
• RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution
• WGK Germany: 2
• RTECS: FZ2275000
• Hazardous Substances Data: 434-13-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Lithocholic acid is used as a chelagogue, which helps to stimulate the flow of bile from the liver to the small intestine. This aids in the digestion and absorption of fats and fat-soluble vitamins.
Used in Cholelithogenic Research:
Lithocholic acid is used as an anticholelithogenic agent, which helps to prevent the formation of gallstones. It is used in studies to investigate the underlying mechanisms and factors contributing to gallstone formation.
Used in Cholestasis Research:
Lithocholic acid has been used in a study to assess cholestasis and its action on several organs and tissues in rats. This helps in understanding the effects of cholestasis on the body and potential treatments.
Used in Hepatic Phospholipid and Bile Acid Homeostasis Research:
Lithocholic acid has been used in a study to investigate the regulation of hepatic phospholipid and bile acid homeostasis through SMAD3 activation by TGFβ. This research contributes to the understanding of the complex interactions between bile acids, phospholipids, and signaling pathways in the liver.
Toxicity:
The LD50 (mouse) value for lithocholic acid is 3900 mg/kg when administered orally, indicating its relative safety when used in appropriate doses.

Air & Water Reactions

Insoluble in water.

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition LITHOCHOLIC ACID emits acrid smoke and fumes.

Fire Hazard

Flash point data for LITHOCHOLIC ACID are not available. LITHOCHOLIC ACID is probably combustible.

Biological Activity

lithocholic acid (lca) is a toxic secondary bile acid, causing intrahepatic cholestasis, which has tumor-promoting activity.

in vitro

among 17 kinds of bile acids with respect to inhibition of mammalian dna polymerases, only lca and its derivatives inhibited dna polymerases, while other bile acids did not show inhibitory effect [1].

in vivo

administration of lca and its conjugates to rodents causes intrahepatic cholestasis, which is a pathogenic state characterized by decreased bile flow and the accumulation of bile constituents in the liver and blood [2].

Purification Methods

Lithocholic acid can be purified by conversion to the rather insoluble Na or K salt by addition of the equivalent amount of aqueous NaOH or KOH, filtering off the alkali salt, washing it with ice cold H2O, dissolving it in the least volume of boiling H2O, acidifying with the dilute HCl (slight excess), filtering off the acid, washing with cold H2O and drying it thoroughly in a vacuum. Recrystallise it from Me2CO, EtOH or acetic acid. The methyl ester crystallises from MeOH, with 0.5 mol of MeOH, and has m 92-93o, [] D 25 +34o (MeOH). It has also been purified by recrystallisation from pet ether (b 40-60o) and, after chromatography on Al2O3 in pet ether, gave a labile form m 92-93o which is transformed to the stable form m 125-126o after standing for 2days in a vacuum desiccator. [Hoelm & Mason J Am Chem Soc 62 569 1940, Sarel & Yanuka J Org Chem 24 2018 1959, Beilstein 10 IV 785.]

references

[1] ogawa a, murate t, suzuki m, nimura y, yoshida s. lithocholic acid, a putative tumor promoter, inhibits mammalian dna polymerase beta. jpn j cancer res. 1998 nov;89(11):1154-9.[2] staudinger jl, goodwin b, jones sa, hawkins-brown d, mackenzie ki, latour a, liu y, klaassen cd, brown kk, reinhard j, willson tm, koller bh, kliewer sa. the nuclear receptor pxr is a lithocholic acid sensor that protects against liver toxicity. proc natl acad sci u s a. 2001 mar 13;98(6):3369-74.

InChI:InChI=1/C24H40O3/c1-15(4-9-22(26)27)19-7-8-20-18-6-5-16-14-17(25)10-12-23(16,2)21(18)11-13-24(19,20)3/h15-21,25H,4-14H2,1-3H3,(H,26,27)/p-1/t15-,16-,17-,18+,19-,20+,21+,23+,24-/m1/s1

Upstream product

• 64-17-5 ethanol 
• 859-97-2 3,7-diketocholanic acid 
• 563-41-7 semicarbazide hydrochloride 
• 127-09-3 sodium acetate 
• 3664-87-7 3α-hydroxy-5β-chol-6-en-24-oic acid 
• 141-52-6 sodium ethanolate 
• 18207-68-6 3α-(3-carboxy-propionyloxy)-7,12-dioxo-5β-cholanoic acid-(24)-methyl ester 
• 1452-33-1 methyl 3-oxo-4-cholenolate 
• 5130-29-0 12-oxolithocholic acid 
• 4651-66-5 methyl 3α-acetoxy-11-oxo-5β-cholan-24-oate 
• 7753-73-3 Methyl 3α-acetyloxy-7,12-dioxo-5β-cholan-24-oate 
• 17225-41-1 3α-benzoyloxy-12-oxo-5β-cholanoic acid-(24)-methyl ester 
• 21059-42-7 3α-ethoxycarbonyloxy-7,12-dioxo-5β-cholan-24-oic acid methyl ester 
• 118763-47-6 3α,6α-diacetoxy-7,7-ethanediyldimercapto-5β-cholan-24-oic acid 

Downstream Products

• 28083-35-4 5β.14β.17βH.20ξH-cholen-(3)-oic acid-(24) 
• 42737-20-2 5-beta‐chol‐2‐en‐24‐oic acid 
• 28083-35-4 5β-chol-3-en-24-oic acid 
• 13164-19-7 glycolithocholic acid 
• 1249-75-8 methyl lithocholate 
• 1553-56-6 dehydrolithocholic acid 
• 6112-82-9 ethyl 3α-hydroxy-5β-cholan-24-oate 
• 6112-83-0 benzyl (R)-4-((3R,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate 
• 75672-10-5 p-nitrophenyl lithocholate 
• 89846-42-4 N-(phenyl)-3α-hydroxy-5β-cholan-24-amide 
• 126784-20-1 3aα-H-4α-<3'-propionic acid>-5α-hydroxy-7aβ-methyl-hexahydro-1-indanone-δ-lactone 
• 80724-92-1 2'-(3α-Hydroxy-24-norcholan-23-yl)-4',4'-dimethyl-4',5'-dihydrooxazole 
• 87826-99-1 (R)-4-((3R,5R,8R,9S,10S,13R,14S,17R)-3-((3-carboxypropanoyl)oxy)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid 
• 181633-70-5 3α-Trifluoroacetoxy-5β-cholan-24-oic acid 

Relevant articles and documents

Determination of sulfated and nonsulfated bile acids in serum by mass fragmentography

A Sep-Pak C18 cartridge was used for purification of bile acids from serum. Three kinds of deuterium labeled internal standards were required for accurate measurement of individual sulfated and nonsulfated bile acids. These internal standards were added to the serum before its application to the cartridge. Separation of sulfated and nonsulfated bile acids was performed on piperidinohydroxypropyl Sephadex LH-20 column chromatography. The nonsulfate fraction was submitted to alkaline hydrolysis, and the sulfate fraction to solvolysis followed by alkaline hydrolysis. Each fraction was converted to the hexafluoroisopropyl-trifluoroacetyl derivatives and quantitated by mass fragmentography. The recovery of each bile acid sulfate was quite satisfactory. In fasting healthy subjects the mean of total nonsulfated bile acids in serum was 1.324 μg/ml, and that of total sulfated bile acids was 0.450 μg/ml. Sulfated lithocholic aid comprised a large part of sulfated bile acids in healthy subjects.

Preparation method of lithocholic acid and intermediates thereof

The invention discloses a synthesis method of lithocholic acid and an intermediates thereof. According to the preparation method of the lithocholic acid intermediate, a compound I reacts with hydrogento generate a compound II in a mixed solvent by taking palladium on carbon as a catalyst and adding specific alkali; a low-price botanical bulk fermentation product BA is used as a raw material, andlithocholic acid is synthesized through side chain construction, hydrogenation, reduction, hydrolysis and other reactions; and the selectivity of 5beta hydrogen in the hydrogenation reaction is improved, high-toxicity reagents such as hydrazine hydrate are prevented from being used for hydroxyl due to removal of other animal-derived cholic acids, and the method is environmentally friendly, high insafety, simple in route, mild in reaction condition and suitable for industrial mass production.

METHOD FOR HOMOGENIZING BILE ACID DERIVATIVES

The present invention relates to a process for producing bile acid derivatives having a protected hydroxyl group in the 3 position comprising contacting a bile acid derivative having an unprotected 3-alpha-hydroxyl group with a specific lipase. The present invention further relates to a bile acid derivative obtained or obtainable by the process, to the use of the bile acid derivative obtained or obtainable by the process for producing lithocholic acid and also to a process for producing lithocholic acid and to lithocholic obtained by the process. The invention further relates to the use of lithocholic acid obtained or obtainable by the process for producing ursodeoxycholic acid or ursodeoxycholic acid derivatives.

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.

Method for synthesizing lithocholic acid by taking BA as raw material

The invention discloses a method for synthesizing lithocholic acid. According to the method, 21-hydroxy-20-methylpregn-4-en-3-one (BA) is used as a raw material and successively subjected to an oxidation reaction, a Wittig reaction and a reduction reaction to synthesize lithocholic acid. The method for synthesizing lithocholic acid has the advantages of environmental protection, simple steps, fewside reactions, high yield, usage cheap and easily available raw materials, and suitableness for industrial production, and overcomes the problems of high synthesis cost, low yield and unsuitability for large-scale industrial production in the prior art.

ISOLITHOCHOLIC ACID OR ISOALLOLITHOCHOLIC ACID AND DEUTERATED DERIVATIVES THEREOF FOR PREVENTING AND TREATING CLOSTRIDIUM DIFFICILE-ASSOCIATED DISEASES

The present invention relates to isolithocholic acid (3?-hydroxy-5?-cholan-24-oic acid, iso-LCA) and isoallolithocholic acid (3?-hydroxy-5α-cholan-24-oic acid) and their deuterated analogs for preventing or treating Clostridium difficile-associated disease in a mammalian subject.

3-MODIFIED ISO-/ISOALLO-LITHOCHOLIC ACID DERIVATIVES OR THEIR HOMO-ANALOGS FOR PREVENTING AND TREATING CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DISEASES

The present invention relates to isolithocholic acid (3β-hydroxy-5β-cholan-24-oic acid) and isoallolithocholic acid (3β-hydroxy-5α-cholan-24-oic acid) together with the respective 22-homo-analogs or the deuterated analogs, which are modified in 3-position

Optimization of EphA2 antagonists based on a lithocholic acid core led to the identification of UniPR505, a new 3α-carbamoyloxy derivative with antiangiogenetic properties

The EphA2 receptor has been validated in animal models as new target for treating tumors depending on angiogenesis and vasculogenic mimicry. In the present work, we extended our current knowledge on structure-activity relationship (SAR) data of two related classes of antagonists of the EphA2 receptor, namely 5β-cholan-24-oic acids and 5β-cholan-24-oyl L-β-homotryptophan conjugates, with the aim to develop new antiangiogenic compounds able to efficiently prevent the formation of blood vessels. As a result of our exploration, we identified UniPR505, N-[3α-(Ethylcarbamoyl)oxy-5β-cholan-24-oyl]-L-β-homo-tryptophan (compound 14), as a submicromolar antagonist of the EphA2 receptor capable to block EphA2 phosphorylation and to inhibit neovascularization in a chorioallantoic membrane (CAM) assay.

Method for synthesizing lithocholic acid from hyodeoxycholic acid as raw material

The invention discloses a method for synthesizing a lithocholic acid from a hyodeoxycholic acid as the raw material. The hyodeoxycholic acid is used as the starting material, the lithocholic acid is produced through the seven reaction steps of 24-carboxylesterification, carboxylation of 3alpha-hydroxyl and 6alpha-hydroxyl through oxidation, selective reduction, acylation, hydrazone formation, hydrazoneremoval, and hydrolysis. The starting material is cheap and easy to get, no hydrazine hydrate is used in the synthesis process, the technological conditions for synthesis are safe, environmentally friendly and mild, the total yield is relatively high, and the method is suitable for industrial production.

Method for synthesizing lithocholic acid from deoxycholic acid as raw material

The invention belongs to the field of organic chemicals, relates to a method for synthesizing lithocholic acid, and in particular relates to a method for synthesizing lithocholic acid from deoxycholicacid as a raw material. The method comprises the following steps: by taking deoxycholic acid as an initial raw material; carrying out oxidation and a hydrazone generation reaction, and further carrying out a reduction reaction, thereby obtaining the lithocholic acid. The method provided by the invention is low in initial raw material price, easy in raw material obtaining, short in synthesis stepand is a completely novel synthesis route; reagents used in the method are easy to preserve and safe and nontoxic, and the method is gentle in reaction condition, simple in aftertreatment, high in efficiency and total yield and applicable to industrial production.