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Chemical Synthesis of Uncommon Natural Bile Acids: The 9α-Hydroxy Derivatives of Chenodeoxycholic and Lithocholic Acids
- Source :
- CHEMICAL & PHARMACEUTICAL BULLETIN. 64:1397-1402
- Publication Year :
- 2016
- Publisher :
- Pharmaceutical Society of Japan, 2016.
-
Abstract
- The chemical synthesis of the 9α-hydroxy derivatives of chenodeoxycholic and lithocholic acids is reported. For initiating the synthesis of the 9α-hydroxy derivative of chenodeoxycholic acid, cholic acid was used; for the synthesis of the 9α-hydroxy derivative of lithocholic acid, deoxycholic acid was used. The principal reactions involved were (1) decarbonylation of conjugated 12-oxo-Δ(9(11))-derivatives using in situ generated monochloroalane (AlH2Cl) prepared from LiAlH4 and AlCl3, (2) epoxidation of the deoxygenated Δ(9(11))-enes using m-chloroperbenzoic acid catalyzed by 4,4'-thiobis-(6-tert-butyl-3-methylphenol), (3) subsequent Markovnikov 9α-hydroxylation of the Δ(9(11))-enes with AlH2Cl, and (4) selective oxidation of the primary hydroxyl group at C-24 in the resulting 3α,9α,24-triol and 3α,7α,9α,24-tetrol to the corresponding C-24 carboxylic acids using sodium chlorite (NaClO2) in the presence of a catalytic amount of 2,2,6,6-tetramethylpiperidine 1-oxyl free radical (TEMPO) and sodium hypochlorite (NaOCl). The (1)H- and (13)C-NMR spectra are reported. The 3α,7α,9α-trihydroxy-5β-cholan-24-oic acid has been reported to be present in the bile of the Asian bear, and its 7-deoxy derivative is likely to be a bacterial metabolite. These bile acids are now available as authentic reference standards, permitting their identification in vertebrate bile acids.
- Subjects :
- 0301 basic medicine
Biological Products
Lithocholic acid
Chemistry
Decarbonylation
Sodium chlorite
Deoxycholic acid
Markovnikov's rule
Molecular Conformation
Cholic acid
General Chemistry
General Medicine
Chenodeoxycholic Acid
Chemical synthesis
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
Chenodeoxycholic acid
Drug Discovery
Organic chemistry
Lithocholic Acid
Subjects
Details
- ISSN :
- 13475223 and 00092363
- Volume :
- 64
- Database :
- OpenAIRE
- Journal :
- CHEMICAL & PHARMACEUTICAL BULLETIN
- Accession number :
- edsair.doi.dedup.....670472e45d4ee5df3c91c8208ac87485