911-40-0

Usage

Uses

Used in Organic Synthesis:
7-Ketodeoxycholic Acid is used as a key intermediate in the synthesis of various organic compounds. Its unique structure allows for the formation of new chemical bonds and the modification of existing ones, making it a versatile building block for the development of new molecules with potential applications in various industries.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 7-Ketodeoxycholic Acid is used as a starting material for the synthesis of drug candidates. Its ability to form new chemical entities makes it a valuable asset in the development of novel therapeutic agents with improved efficacy and reduced side effects.
Used in Chemical Research:
7-Ketodeoxycholic Acid is also used in chemical research to study the properties and reactivity of bile acids and their derivatives. This knowledge can contribute to a better understanding of the role of bile acids in various biological processes and the development of new strategies for the treatment of related disorders.

InChI:InChI=1/C24H38O5/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/h13-18,20,22,25,27H,4-12H2,1-3H3,(H,28,29)/t13-,14+,15-,16-,17+,18+,20+,22+,23+,24-/m1/s1

Upstream product

• 81-25-4 cholic acid 
• 21066-20-6 methyl 7-dehydrocholate diacetate (methyl 3α,12α-diacetoxy-7-oxo-5β-cholan-24-oate) 
• 64-19-7 acetic acid 
• 67-64-1 acetone 
• 79-15-2 N-bromoacetamide 
• 81-23-2 dehydrocholic acid 
• 361-09-1 sodium cholate 
• 7732-18-5 water 
• 128-08-5 N-Bromosuccinimide 
• 127-09-3 sodium acetate 
• 623-11-0 1-methyl-4-nitrosobenzene 
• 863-57-0 sodium glycocholate 
• 145-42-6 sodium taurocholate 
• 1448-36-8 methyl cholate 

Downstream Products

• 15073-97-9 methyl 3α,12α-dihydroxy-7-oxo-5β-cholate 
• 109845-11-6 3α.12α-diformyloxy-7-oxo-5β-cholanoic acid-(24) 
• 21059-38-1 3α,12α-dihydroxy-7-oxo-5β-cholan-24-oic acid ethyl ester 
• 115487-85-9 (R)-4-((3R,5S,8R,9S,10S,12S,13R,14S,17R)-3,12-Dihydroxy-10,13-dimethyl-7-oxo-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoic acid 4-nitro-phenyl ester 
• 2955-27-3 ursocholic acid 
• 162850-28-4 methyl 3α,12α-bis((1-pyrenoyl)oxy)-7-keto-5β-cholan-24-oate 
• 13535-96-1 3-oxo-12α-hydroxy-4,6-choladien-24-oic acid 
• 1204197-61-4 7α-amino-3α,12α-dihydroxy-5β-cholan-24-oic acid methyl ester hydrochloride 
• 1204197-64-7 7α-amino-3α,12α-dihydroxy-5β-cholan-24-oic acid methyl ester 
• 138566-73-1 C₂₄H₄₁NO₄ 
• 145682-73-1 C₂₆H₄₅NO₈S 

Relevant academic research and scientific papers

Synthesis method of intermediate 3 α - hydroxyl -7 - ketone - 5 5 5 beta-cholestane -24 - acid of obeticholic acid

The invention discloses a chemical synthesis method for an intermediate 7-ketone lithocholic acid(3alpha-hydroxy-7-ketone-5beta-cholestane-24-acid) of obeticholic acid, and belongs to the field of organic chemical synthesis. The method comprises the following steps: cholic acid is taken as a raw material, and the intermediate 7- ketone lithocholic acid of the obeticholic acid is synthesized through the selective oxidation of 7alpha-hydroxy, the benzyl esterification of side chain carboxyl, the etherification of 3alpha-hydroxy, the methanesulfonic acid esterification of 12alpha-hydroxy, elimination, hydrogenation, hydrolysis and the like. The method disclosed by the invention has the advantages of novel synthetic method, low cost, high yield, environment friendliness and convenience in industrial production since the cheap cholic acid is taken as the raw material.

SYNTHETIC DERIVATIVES OF CHOLIC ACID 7-SULFATE AND USES THEREOF

The compositions and methods provided herein are related, in part, to the discovery of cholic acid 7-sulfate as a treatment for diabetes. Provided herein is a method for treating a metabolic disorder (e.g., diabetes, obesity), or an inflammatory disease (e.g., Crohn's disease, inflammatory bowel disease, ulcerative colitis, pancreatitis, hepatitis, appendicitis, gastritis, diverticulitis, celiac disease, food intolerance, enteritis, ulcer, gastroesophageal reflux disease (GERD), psoriatic arthritis, psoriasis, and rheumatoid arthritis) in a subject in need thereof comprising administering to a subject a compound of Formulae (I)-(XVII).

Insights into the Substrate Promiscuity of Novel Hydroxysteroid Dehydrogenases

Hydroxysteroid dehydrogenases (HSDHs) are valuable biocatalysts for the regio- and stereoselective modification of steroids, bile acids and other steroid derivatives. In this work, we investigated the substrate promiscuity of this highly selective class of enzymes. In order to reach this goal, a preliminary search of HSDH homologues in in-house or public available (meta)genomes was carried out. Eight novel NAD(H)-dependent HSDHs, showing either 7α-, 7β-, or 12α-HSDH activity, and including, for the first time, enzymes from extremophilic microorganisms, were identified, recombinantly produced, and characterized. Among the novel HSDHs, four highly active (up to 92 U mg?1) NAD(H)-dependent 7β-HSDHs showing negligible similarity towards previously described 7β-HSDHs, were discovered. These enzymes, along with previously characterized HSDHs, were tested as biocatalysts for the stereoselective reduction of a panel of substrates including two α-ketoesters of pharmaceutical interest and selected ketones that partially resemble the structural features of steroids. All the reactions were coupled with a suitable cofactor regeneration system. Regarding the α-ketoesters, nearly all of the tested HSDHs showed a good activity toward the selected substrates, yielding the reduced α-hydroxyester with up to 99% conversions and enantiomeric excesses. On the other hand, only the 7β-HSDHs from Collinsella aerofaciens and Clostridium absonum showed appreciable activity toward more complex ketones, i. e., (±)-trans-1-decalone, but with interesting as well as different selectivity. (Figure presented.).

NAD+-Dependent Enzymatic Route for the Epimerization of Hydroxysteroids

Epimerization of cholic and chenodeoxycholic acid (CA and CDCA, respectively) is a notable conversion for the production of ursodeoxycholic acid (UDCA). Two enantiocomplementary hydroxysteroid dehydrogenases (7α- and 7β-HSDHs) can carry out this transformation fully selectively by specific oxidation of the 7α-OH group of the substrate and subsequent reduction of the keto intermediate to the final product (7β-OH). With a view to developing robust and active biocatalysts, novel NADH-active 7β-HSDH species are necessary to enable a solely NAD+-dependent redox-neutral cascade for UDCA production. A wild-type NADH-dependent 7β-HSDH from Lactobacillus spicheri (Ls7β-HSDH) was identified, recombinantly expressed, purified, and biochemically characterized. Using this novel NAD+-dependent 7β-HSDH enzyme in combination with 7α-HSDH from Stenotrophomonas maltophilia permitted the biotransformations of CA and CDCA in the presence of catalytic amounts of NAD+, resulting in high yields (>90 %) of UCA and UDCA.

Efficient Synthesis of 12-Oxochenodeoxycholic Acid Using a 12α-Hydroxysteroid Dehydrogenase from Rhodococcus ruber

12α-Hydroxysteroid dehydrogenase (12α-HSDH) has the potential to convert cheap and readily available cholic acid (CA) to 12-oxochenodeoxycholic acid (12-oxo-CDCA), a key precursor for chemoenzymatic synthesis of the therapeutic bile acid ursodeoxycholic acid (UDCA). In this work, a native nicotinamide adenine dinucleotide (NAD+)-dependent 12α-hydroxysteroid dehydrogenase (Rr12α-HSDH) from Rhodococcus ruber was identified using a structure-guided genome mining (SSGM) approach, which is based on the structure of cofactor pocket and the conserved nicotinamide cofactor binding motif alignment. Rr12α-HSDH was heterologously overexpressed in Escherichia coli BL21 (DE3), purified and characterized. The purified Rr12α-HSDH showed a high oxidative activity of 290 U mg?1protein toward CA, with a catalytic efficiency (kcat/KM) of 5.10×103 mM?1 s?1. In a preparative biotransformation (100 mL), CA (200 mM, 80 g L?1) was efficiently converted to 12-oxo-CDCA in 1 h, with a 85% isolated yield and a space-time yield (STY) of up to 1632 g L?1 d?1. Furthermore, Rr12α-HSDH was shown to be able to catalyze the oxidation of other 12α-hydroxysteroids at high substrate loads (up to 200 mM), giving the corresponding 12-oxo-hydroxysteroids in 71%–85% yields, indicating the great potential of Rr12α-HSDH as a promising biocatalyst for the synthesis of various therapeutic bile acids. (Figure presented.).

A facile synthesis of ursodeoxycholic acid and obeticholic acid from cholic acid

A novel synthetic route of producing ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) was developed through multiple reactions from cheap and readily-available cholic acid. The reaction conditions of the key elimination reaction of mesylate ester group were also investigated and optimized, including solvent, base and reaction temperature. In the straightforward synthetic route for preparation of UDCA and OCA, most of the reaction steps have high conversions with average yields of 94% and 92%, and overall yield up to 65% (7 steps) and 36% (11 steps) from cholic acid, respectively. This promising route offers economical and efficient strategies for potential large-scale production of UDCA and OCA.

Synthesis method of intermediate 7-ketolithocholic acid of ursodeoxycholic acid

The invention discloses a chemical synthesis method of intermediate 7-ketolithocholic acid (3alpha-hydroxy-7-one-5beta-cholestan-2-4-acid) of ursodeoxycholic acid, and belongs to the field of organic chemical synthesis. According to the method, cholic acid is adopted as a material, and is subjected to reactions including selective oxidation of 7alpha-hydroxy, benzyl esterification of a side chain carboxyl group, esterification of 3alpha-hydroxy, methanesulfonic acid esterification of 12alpha-hydroxy, elimination, hydrogenation and hydrolysis to synthesize the intermediate 7-ketolithocholic acid of the ursodeoxycholic acid; the cheap cholic acid is adopted as the material, the synthesis method has the advantages of being novel, low in cost, high in yield and environment-friendly and industrial production is facilitated.

Synthesis method for obeticholic acid intermediate 7-ketolithocholic acid

The invention discloses a chemical synthesis method for an obeticholic acid intermediate 7-ketolithocholic acid (3alpha-hydroxy-7-keto-5beta-cholestane-24-acid), and belongs to the field of organic chemical synthesis. The method adopts cholic acid as a raw material, and through 7alpha-hydroxyl selective oxidation, side chain carboxyl esterification, 3alpha-hydroxyl etherification, 12alpha-hydroxyl methanesulfonic acid esterification, elimination, hydrogenation, hydrolysis and other reactions, the obeticholic acid intermediate 7-ketolithocholic acid is synthesized. The synthesis method for 7-ketolithocholic acid adopts cheap cholic acid as the raw material, and has the advantages of novel synthesis method, low cost, high yield, environmental friendliness and convenience in industrialized production.

Synthetic method of 7-keto-lithocholic acid

The invention discloses a chemical synthetic method of an intermediate 7-keto-lithocholic acid (3alpha-hydroxyl-7-ketone-5beta-cholestane-24-acid) of obeticholic acid, and belongs to the field of organic chemical synthesis. According to the chemical synthetic method of the intermediate 7-keto-lithocholic acid (3alpha-hydroxyl-7-ketone-5beta-cholestane-24-acid) of obeticholic acid, cholic acid is adopted as a raw material, and through reactions of selective oxidization of 7alpha-hydroxyl, esterification of side chain carboxyl groups, esterification of 3alpha-hydroxyl, methanesulfonic acid esterification, elimination, hydrogenation, and hydrolysis of 12alpha-hydroxyl, the intermediate 7-keto-lithocholic acid (3alpha-hydroxyl-7-ketone-5beta-cholestane-24-acid) of obeticholic acid is synthesized. According to the chemical synthetic method of the intermediate 7-keto-lithocholic acid (3alpha-hydroxyl-7-ketone-5beta-cholestane-24-acid) of obeticholic acid, cheap cholic acid is adopted as the raw material, the synthesis method is novel, low in cost, high in yield and environmentally friendly, which facilitates industrialized production.

[...] synthetic method and intermediate (by machine translation)

The invention discloses a method for synthesizing [...], the cholic acid as the raw material, after 7 α - hydroxy selective oxidation, side chain carboxyl ester, 3 α - hydroxy ester, 12 α - hydroxy methanesulfonic acid esterification, eliminate, selective hydrolysis of 3 bit ester group, with the three-a chlorosilane reaction to produce the silicon ether, with acetaldehyde to aldol condensation, and the hydrolysis, catalytic hydrogenation reduction olefinic bond, carbonyl reduction reaction such as, to synthesize states the aobeiaobei cholic acid. The method of the invention uses cheap cholic acid as raw materials, synthetic method is novel, low cost, high yield, mild reaction conditions, easy post treatment, environmental friendly, convenient to industrial production. (by machine translation)