81-25-4Relevant articles and documents
METHODS FOR PREPARING BILE ACIDS
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Paragraph 219; 220, (2019/02/15)
The present disclosure provides methods of preparing cholic acid, deoxycholic acid, or chenodeoxycholic acid, an ester thereof, or a pharmaceutically or cosmetically acceptable salt thereof, and novel and useful synthetic intermediates, for example, as described for methods 1, 1A, 1B, 2, 3, 3A, and 4. The method can start with a plant derived steroid as a starting material, such as dehydroepiandrosterone (DHEA) or Acetyl-dehydroepiandrosterone (Ac-DHEA). Also provided are pharmaceutical or cosmetic compositions and uses thereof, which comprise one or more of cholic acid, deoxycholic acid, or chenodeoxycholic acid, an ester thereof, or a pharmaceutically or cosmetically acceptable salt thereof, which is of high purity, for example, free of animal derived impurities.
A DNA-conjugated small molecule catalyst enzyme mimic for site-selective ester hydrolysis
Flanagan, Moira L.,Arguello, A. Emilia,Colman, Drew E.,Kim, Jiyeon,Krejci, Jesse N.,Liu, Shimu,Yao, Yueyu,Zhang, Yu,Gorin, David J.
, p. 2105 - 2112 (2018/03/05)
The challenge of site-selectivity must be overcome in many chemical research contexts, including selective functionalization in complex natural products and labeling of one biomolecule in a living system. Synthetic catalysts incorporating molecular recognition domains can mimic naturally-occurring enzymes to direct a chemical reaction to a particular instance of a functional group. We propose that DNA-conjugated small molecule catalysts (DCats), prepared by tethering a small molecule catalyst to a DNA aptamer, are a promising class of reagents for site-selective transformations. Specifically, a DNA-imidazole conjugate able to increase the rate of ester hydrolysis in a target ester by >100-fold compared with equimolar untethered imidazole was developed. Other esters are unaffected. Furthermore, DCat-catalyzed hydrolysis follows enzyme-like kinetics and a stimuli-responsive variant of the DCat enables programmable turn on of the desired reaction.
Deoxycholic acid transformations catalyzed by selected filamentous fungi
Kollerov,Lobastova,Monti,Deshcherevskaya,Ferrandi,Fronza,Riva,Donova
, p. 20 - 29 (2016/03/04)
More than 100 filamentous fungi strains, mostly ascomycetes and zygomycetes from different phyla, were screened for the ability to convert deoxycholic acid (DCA) to valuable bile acid derivatives. Along with 11 molds which fully degraded DCA, several strains were revealed capable of producing cholic acid, ursocholic acid, 12-keto-lithocholic acid (12-keto-LCA), 3-keto-DCA, 15β-hydroxy-DCA and 15β-hydroxy-12-oxo-LCA as major products from DCA. The last metabolite was found to be a new compound. The ability to catalyze the introduction of a hydroxyl group at the 7(α/β)-positions of the DCA molecule was shown for 32 strains with the highest 7β-hydroxylase activity level for Fusarium merismoides VKM F-2310. Curvularia lunata VKM F-644 exhibited 12α-hydroxysteroid dehydrogenase activity and formed 12-keto-LCA from DCA. Acremonium rutilum VKM F-2853 and Neurospora crassa VKM F-875 produced 15β-hydroxy-DCA and 15β-hydroxy-12-oxo-LCA, respectively, as major products from DCA, as confirmed by MS and NMR analyses. For most of the positive strains, the described DCA-transforming activity was unreported to date. The presented results expand the knowledge on bile acid metabolism by filamentous fungi, and might be suitable for preparative-scale exploitation aimed at the production of marketed bile acids.
Hydroxylation of lithocholic acid by selected actinobacteria and filamentous fungi
Kollerov,Monti,Deshcherevskaya,Lobastova,Ferrandi,Larovere,Gulevskaya,Riva,Donova
, p. 370 - 378 (2013/03/28)
Selected actinobacteria and filamentous fungi of different taxonomy were screened for the ability to carry out regio- and stereospecific hydroxylation of lithocholic acid (LCA) at position 7β. The production of ursodeoxycholic acid (UDCA) was for the first time shown for the fungal strains of Bipolaris, Gibberella, Cunninghamella and Curvularia, as well as for isolated actinobacterial strains of Pseudonocardia, Saccharothrix, Amycolatopsis, Lentzea, Saccharopolyspora and Nocardia genera. Along with UDCA, chenodeoxycholic (CDCA), deoxycholic (DCA), cholic (CA), 7-ketodeoxycholic and 3-ketodeoxycholic acids were detected amongst the metabolites by some strains. A strain of Gibberella zeae VKM F-2600 expressed high level of 7β-hydroxylating activity towards LCA. Under optimized conditions, the yield of UDCA reached 90% at 1 g/L of LCA and up to 60% at a 8-fold increased substrate loading. The accumulation of the major by-product, 3-keto UDCA, was limited by using selected biotransformation media.
Regioselective oxidation of cholic acid and its 7β epimer by using o-iodoxybenzoic acid
Dangate, Prasad S.,Salunke, Chetan L.,Akamanchi, Krishnacharya G.
experimental part, p. 1397 - 1399 (2011/11/06)
Rational exploration directed by DFT (density functional theory) based atomic Fukui indices, lead to development of regioselective oxidation of cholic acid and its 7β epimer by o-iodoxybenzoic acid. In case of cholic acid only, 7α-hydroxyl underwent oxidation, where as in its 7β epimer the selectivity was towards 12α-hydroxy group. Since these oxidations are the key steps in synthesis of ursodeoxycholic acid starting from cholic acid these findings may be useful in devising a protection free synthetic route.
Xanthomonas maltophilia CBS 897.97 as a source of new 7β- and 7α-hydroxysteroid dehydrogenases and cholylglycine hydrolase: Improved biotransformations of bile acids
Pedrini, Paola,Andreotti, Elisa,Guerrini, Alessandra,Dean, Mariangela,Fantin, Giancarlo,Giovannini, Pier Paolo
, p. 189 - 198 (2007/10/03)
The paper reports the partial purification and characterization of the 7β- and 7α-hydroxysteroid dehydrogenases (HSDH) and cholylglycine hydrolase (CGH), isolated from Xanthomonas maltophilia CBS 897.97. The activity of 7β-HSDH and 7α-HSDH in the reduction of the 7-keto bile acids is determined. The affinity of 7β-HSDH for bile acids is confirmed by the reduction, on analytical scale, to the corresponding 7β-OH derivatives. A crude mixture of 7α- and 7β-HSDH, in soluble or immobilized form, is employed in the synthesis, on preparative scale, of ursocholic and ursodeoxycholic acids starting from the corresponding 7α-derivatives. On the other hand, a partially purified 7β-HSDH in a double enzyme system, where the couple formate/formate dehydrogenase allows the cofactor recycle, affords 6α-fluoro-3α, 7β-dihydroxy-5β-cholan-24-oic acid (6-FUDCA) by reduction of the corresponding 7-keto derivative. This compound is not obtainable by microbiological route. The efficient and mild hydrolysis of glycinates and taurinates of bile acids with CGH is also reported. Very promising results are also obtained with bile acid containing raw materials.
Regio- and stereoselective reductions of dehydrocholic acid
Cravotto, Giancarlo,Binello, Arianna,Boffa, Luisa,Rosati, Ornelio,Boccalini, Marco,Chimichi, Stefano
, p. 469 - 475 (2007/10/03)
Dehydrocholic acid (DHCA), an unnatural bile acid, is manufactured by oxidation of cholic acid. Its biotransformation by two basidiomycetes (Trametes hirsuta and Collybia velutipes) is reported. These mycelia showed different affinities for the substrate and selectivities of attack: T. hirsuta in particular regio- and stereoselectively reduced the 3-keto group to yield 3α-hydroxy-7,12-diketo-5β-cholan-24-oic acid (7,12-diketolithocolic acid) as the main product. A number of different chemical reductions were carried out on DHCA; among them hydrogenation with Raney Nickel in water under high-intensity ultrasound proved highly regio- and stereoselective, yielding 7,12-diketolithocolic acid exclusively. 1H and 13C resonances were assigned in details thanks to a series of 1D and 2D NMR runs including DEPT, NOESY, H-H COSY, gHSQC and gHMBC.
Chemical modifications of bile acids under high-intensity ultrasound or microwave irradiation
Cravotto, Giancarlo,Boffa, Luisa,Turello, Marta,Parenti, Massimo,Barge, Alessandro
, p. 77 - 83 (2007/10/03)
High-intensity ultrasound (HIU) and microwave (MW) irradiation, having emerged as effective promoters of organic reactions, were exploited for the synthesis of bile acids derivatives. Esterification, amidation, hydrolysis, oxidation, and reduction were investigated. Compared to conventional methods, both techniques proved much more efficient, increasing product yields and dramatically cutting down reaction times. Scaled-up studies are now under way.
Design, synthesis and photochemical properties of caged bile acids
Hirayama, Yuuki,Iwamura, Michiko,Furuta, Toshiaki
, p. 905 - 908 (2007/10/03)
Photolabile derivatives of bile acids (8-10 and 13) were synthesized via silver (I) oxide promoted selective etherification of 3α-hydroxyls. Quantitative production of the parent cholic acid was detected from the photolytic mixture of 3-NB-CA (8) in Tris buffered solution. Interestingly, the unexpectedly stable nitroso-hemiacetal intermediate (14) was detected when the photolysis was conducted in methanol. The enzymatic analysis using 7α-HSDH showed 8 and 9 could serve as caged bile acids that might be able to regulate certain biological processes upon UV irradiation.
SLIME REMOVER AND SLIME PREVENTING/REMOVING AGENT
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, (2008/06/13)
A drainage slime remover capable of spreading a solution of a solid over slime generated wall surface portions, comprising a solid containing a microorganism growth retarding substance and a container which has a shape for permitting the installation thereof at the inlet or upper portion of a drain outlet and stores the solid characterized in that the container has drain flow-in holes having an opening capable of controlling a drain flow-in amount and provided in the upper surface or the upper side portion of the container and solution flow-out holes having an opening capable of controlling a flow-out amount of a solid solution and provided in the bottom or the lower side portion of the container or additionally in the side surface thereof, and a slime preventing/removing agent which can remove slime from portions such as kitchen sinks and bathroom drain outlets where slime is grown by metabolites such as miscellaneous germs and mildews and which can prevent the occurrence of slime safely and for an extended period of time.
