2458-08-4Relevant articles and documents
Preparation and characterization of some keto-bile acid azines
Bertolasi, Valerio,Bortolini, Olga,Fantin, Giancarlo,Fogagnolo, Marco,Perrone, Daniela
, p. 756 - 764 (2007)
New acyclic dimers of ketocholanic acids with hydrazine were obtained. Crystal structure was determined for the 3,7-dihydroxy-12-ketocholanic acid azine. Some distinctive 1H NMR signals are assigned for the entire set of azines.
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Kawai
, p. 71,72 (1933)
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Clean Enzymatic Oxidation of 12α-Hydroxysteroids to 12-Oxo-Derivatives Catalyzed by Hydroxysteroid Dehydrogenase
Tonin, Fabio,Alvarenga, Natália,Ye, Jia Zheng,Arends, Isabel W. C. E.,Hanefeld, Ulf
, p. 2448 - 2455 (2019)
The C12 specific oxidation of hydroxysteroids is an essential reaction required for the preparation of pharmaceutical ingredients like ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA), which can be synthesized by Wolff-Kishner reduction of the obtained 12-oxo-hydroxysteroids. 12α-hydroxysteroid dehydrogenases (12α-HSDHs) have been shown to perform this reaction with high yields, under mild conditions and without the need of protection and deprotection steps, required in chemical synthesis. Here, the recombinant expression and biochemical characterization of the nicotinamide adenine dinucleotide (NAD+)-dependent HSDH from Eggerthella lenta (El12α-HSDH) are reported. This enzyme shows comparable properties with the well-known nicotinamide adenine dinucleotide phosphate (NADP+)-dependent enzyme from Clostridium sp. 48–50. In order to perform a viable and atom efficient enzymatic hydroxysteroid oxidation, NAD(P)H oxidase (NOX) was employed as cofactor regeneration system: NOX uses oxygen (O2) as sacrificial substrate and produces only water as side product. 10 mM of cholic acid was fully and selectively converted to 12-oxo-CDCA in 24 h. The possibility to employ this system on UCA and 7-oxo-deoxycholic acid (7-oxo-DCA) as substrates was additionally investigated. The performance of the El12α-HSDH was evaluated also in combination with a “classical” regeneration system (oxaloacetate/malate dehydrogenase) showing full conversion in 4 h. Finally, the feasibility of a catalytic aerobic-NAD+-dependent enzymatic oxidation was shown on a preparative scale (oxidation of CA to 12-oxo-CDCA) employing the El12α-HSDH-NOX system in a segmented-flow-reactor. (Figure presented.).
Efficient Synthesis of 12-Oxochenodeoxycholic Acid Using a 12α-Hydroxysteroid Dehydrogenase from Rhodococcus ruber
Shi, Shou-Cheng,You, Zhi-Neng,Zhou, Ke,Chen, Qi,Pan, Jiang,Qian, Xiao-Long,Xu, Jian-He,Li, Chun-Xiu
, p. 4661 - 4668 (2019)
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.).
Chenodeoxycholic acid derivative or pharmaceutically acceptable salt thereof, and preparation method and applications thereof
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, (2020/03/12)
The invention discloses a chenodeoxycholic acid derivative with a structure as shown in general formula I or a medicinal salt thereof, and a preparation method and application of the chenodeoxycholicacid derivative. The chenodeoxycholic acid derivative can up-regulate the transcription levels of FXR mRNA and SHP mRNA, can obviously activate FXR, and can be used for preparing drugs for treating orpreventing hyperlipidemia, atherosclerosis, non-alcoholic steatohepatitis, type II diabetes mellitus and other diseases related to blood fat.
