28535-81-1Relevant articles and documents
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Plattner,Heusser
, p. 748,756 (1944)
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Engineering Regioselectivity of a P450 Monooxygenase Enables the Synthesis of Ursodeoxycholic Acid via 7β-Hydroxylation of Lithocholic Acid
Grobe, Sascha,Badenhorst, Christoffel P. S.,Bayer, Thomas,Hamnevik, Emil,Wu, Shuke,Grathwol, Christoph W.,Link, Andreas,Koban, Sven,Brundiek, Henrike,Gro?johann, Beatrice,Bornscheuer, Uwe T.
, p. 753 - 757 (2020/12/01)
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.
Chenodeoxycholic acid derivatives, preparation method thereof and medical application thereof
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, (2018/06/26)
The invention relates to the field of medicinal chemistry, relates to chenodeoxycholic acid derivatives, a preparation method thereof and a medical application thereof, in particular to a kind of chenodeoxycholic acid derivatives with a general formula of (I), a preparation method thereof, a pharmaceutical composition comprising the compounds and medical application thereof, especially used as drugs for preventing or treating hyperlipidaemia, type II diabetes, atherosis and non-alcoholic steatohepatitis. The formula is shown in the description.
Chemical synthesis of uncommon natural bile acids: The 9α-hydroxy derivatives of chenodeoxycholic and lithocholic acids
Iida, Takashi,Namegawa, Kazunari,Nakane, Naoya,Iida, Kyoko,Hofmann, Alan Frederick,Omura, Kaoru
, p. 1397 - 1402 (2016/10/03)
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-Δ9(11)-derivatives using in situ generated monochloroalane (AlH2Cl) prepared from LiAlH4 and AlCl3, (2) epoxidation of the deoxygenated Δ9(11)-enes using m-chloroperbenzoic acid catalyzed by 4,4'-thiobis-(6-tert-butyl-3-methylphenol), (3) subsequent Markovnikov 9a-hydroxylation of the Δ9(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 1H- and 13C-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.