A chemical-enzyme method of preparing ursodeoxycholic acid

A technology for the preparation of ursodeoxycholic acid and enzymatic method, which is applied in the field of chemical-enzymatic preparation of ursodeoxycholic acid, can solve the problems of low product ee, increased cost, and reduced yield, and achieve low overall cost and improved The effect of ee value

Active Publication Date: 2016-11-09
ENZYMEWORKS
View PDF5 Cites 24 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chemical methods usually use oxidants such as NBS, and reducing agents such as sodium borohydride or sodium alkoxide. The problem is that the product ee is not high, usually only 90%, so additional post-processing steps are required, which reduces the yield and increases the cost. (Formula 4)

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A chemical-enzyme method of preparing ursodeoxycholic acid
  • A chemical-enzyme method of preparing ursodeoxycholic acid
  • A chemical-enzyme method of preparing ursodeoxycholic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Embodiment 1 prepares 7-KLCA

[0026] Add 5 g of CDCA and 2 g of tartaric acid into 50 ml of methanol, and stir at room temperature for 10 minutes. Slowly add 25mL of sodium hypochlorite solution (active chlorine 5%) dropwise, and the dropwise addition is completed in 3 hours, and continue to stir for 5 hours. The reaction is monitored by HPLC, and the conversion rate is 99%. After the reaction, 0.5 g of sodium sulfite was added, after stirring, 200 mL of water was added, and 5 g of 7-KLCA was obtained by filtration with a content of 95%.

Embodiment 2

[0027] Embodiment 2 prepares UDCA

[0028] Add 5g 7-KLCA, 4g glucose monohydrate, 45mL 0.1M PBS buffer solution with pH 6.5 to a 100mL three-neck reaction flask, place in a 35°C water bath, and stir mechanically at 400-450rpm for 5min;

[0029] Add 5 mL of n-hexanol and 0.25 mL of Triton X-100 to the reaction flask, and after stirring evenly, add 0.1 g of 7-KLCA reductase (obtained by expressing sequence 20 in Escherichia coli) and glucose dehydrogenation Enzyme (from Suzhou Hanzyme Biotechnology Co., Ltd., No. EW002) 0.1g, NADP 0.005g, start the reaction, use 1M NaOH solution to control the pH at 6.5±0.1 during the reaction. After 4 hours, the reaction is completed, adjust the pH to 3.0, etc. The volume of ethyl acetate was extracted three times, the organic phase was combined, the pH was adjusted to 9.5, the equal volume of water was extracted three times, the aqueous phase was combined, and 4.7 g of the product was obtained by rotary evaporation. The product content was 95%...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

A chemical-enzyme method of preparing ursodeoxycholic acid is disclosed. The method adopts chenodeoxycholic acid as an initial substrate, and prepares the ursodeoxycholic acid through a chemical process and a bio-enzyme process in order, wherein 7-KLCA reductase is adopted as a biological catalyst. A situation that an oxidant residual in a process of preparing 7-ketolithocholic acid through a chemical manner causes later enzyme inactivation in the prior art does not occur. A product prepared by the method is high in ee value and low in comprehensive cost.

Description

technical field [0001] The invention relates to the field of pharmacy, in particular to a chemical-enzymatic method for preparing ursodeoxycholic acid. Background technique [0002] Ursodeoxycholic acid (Ursodeoxycholic Acid, UDCA) structure is shown in formula 1, used for the treatment of cholesterol-type gallstone formation and steatorrhea due to lack of bile, and can also be used for the prevention of drug-induced stone formation. [0003] [0004] Among the currently disclosed methods for preparing ursodeoxycholic acid, the method of "draining live bears for bile extraction" is restricted because it conflicts with wildlife protection regulations and violates humanitarianism. Therefore, there are many reports on methods for extracting bile acids, such as chenodeoxycholic acid (CDCA) from poultry bile and converting them into ursodeoxycholic acid (Formula 2). For example, patent CN201210473483 etc. have reported that CDCA is enzymatically oxidized to 7-ketolithocholic ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C12P33/06C07J9/00
CPCC07J9/005C12P33/06
Inventor 张跃
Owner ENZYMEWORKS
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap