Preparation method of plant-derived 7-ketolithocholic acid

A cornerstone cholic acid and cornerstone technology, which is applied in the field of preparation of plant-sourced 7-ketolithocholic acid, can solve the problems of chenodeoxycholic acid and cholic acid source limitations, viruses brought into downstream products, and human impact, etc., to achieve reduction The effect of good effect, good purity and wide source

Active Publication Date: 2022-01-25
HUNAN KEREY BIOTECH
View PDF13 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The method in the prior art to prepare 7-ketolithocholic acid has the following technical problems: in the past, 7-ketolithocholic acid was mainly prepared from chenodeoxycholic acid or cholic acid from animal viscera through a series of chemical synthesis, and the extracted chenodeoxycholic acid The sources of deoxycholic acid and cholic acid are limited, generally the purity is not high, and may carry viruses into downstream finished products, causing certain impact on the human body

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
  • Preparation method of plant-derived 7-ketolithocholic acid
  • Preparation method of plant-derived 7-ketolithocholic acid
  • Preparation method of plant-derived 7-ketolithocholic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Add 300ml of water in a clean reaction bottle, add 50.0g of compound I (purity: 99.1%) under stirring, adjust pH=13~14 with 2N sodium hydroxide, after compound I is completely dissolved, adjust pH= with 3N hydrochloric acid 8~9. Adjust the reaction temperature to 30-35° C., add 120 g of glucose, 10 g of 3α reductase, 22 g of glucose dehydrogenase, 1.5 g of coenzyme 1, and 1.5 g of coenzyme 2. After stirring evenly, use 2N sodium hydroxide solution to adjust the pH to 7-8 and react for 2 hours until the content of Compound I is 0.1% as monitored by HPLC. After the reaction is finished, the temperature of the system is raised to 70-80°C, and the temperature is kept and stirred for 30-60 minutes. Suction filtration while it is hot, collect the filtrate, heat the filter cake again to 70-80°C with 100ml of water, keep stirring for 30min-60min, heat filter and combine the filtrate. Cool the filtrate to 0-10°C, slowly add 2N hydrochloric acid dropwise to adjust pH = 2-3, a l...

Embodiment 2

[0027] Add 300ml of water to a clean reaction bottle, add 50.0g of compound I (purity: 99.1%) and 50.0ml of glycerin under stirring, adjust the pH to 7~8 with 2N sodium hydroxide, and adjust the reaction after compound I is completely dissolved At a temperature of 30-35°C, add 120g of glucose, 10g of 3α reductase, 22g of glucose dehydrogenase, 1.5g of coenzyme 1, and 1.5g of coenzyme 2. After stirring evenly, use 2N sodium hydroxide solution to adjust the pH to 7-8 and react for 2 hours until the content of Compound I is 0.1% as monitored by HPLC. After the reaction is finished, the temperature of the system is raised to 70-80°C, and the temperature is kept and stirred for 30-60 minutes. Suction filtration while it is hot, collect the filtrate, heat the filter cake again to 70-80°C with 100ml of water, keep stirring for 30min-60min, heat filter and combine the filtrate. Concentrate the filtrate under reduced pressure at 50-60°C to remove all glycerin, cool down to 0-10°C, slo...

Embodiment 3

[0029] Add 300ml of water into a clean reaction bottle, add 50.0g of compound I (purity: 99.1%) and 50.0ml of 2-methyltetrahydrofuran under stirring, adjust the pH to 7~8 with 2N sodium hydroxide, and wait until compound I is completely dissolved , adjust the reaction temperature to 30-35° C., add 120 g of glucose, 10 g of 3α reductase, 22 g of glucose dehydrogenase, 1.5 g of coenzyme I, and 1.5 g of coenzyme II. After stirring evenly, use 2N sodium hydroxide solution to adjust the pH to 7-8 and react for 2 hours until the content of Compound I is 0.1% as monitored by HPLC. After the reaction is finished, the temperature of the system is raised to 70-80°C, and the temperature is kept and stirred for 30-60 minutes. Suction filtration while it is hot, collect the filtrate, heat the filter cake again to 70-80°C with 100ml of water, keep stirring for 30min-60min, heat filter and combine the filtrate. Concentrate the filtrate under reduced pressure at 50-60°C to remove 2-methyltet...

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

PropertyMeasurementUnit
purityaaaaaaaaaa
purityaaaaaaaaaa
Login to view more

Abstract

The invention provides a preparation method of plant-derived 7-ketolithocholic acid, which comprises the following steps: by taking 3,7-diketone-5beta-cholestane-24-acid shown in a formula I as a raw material, reacting in 3 alpha reductase and a system containing alkaline water to generate the 7-ketolithocholic acid shown in a formula II. According to the invention, 3,7-diketone-5beta-cholestane-24-acid prepared from a plant source fermentation product BA through a series of synthesis is taken as a starting material, so that a plant source total synthesis route is opened, and monopoly of animal sources is broken. The starting raw materials are wide in source, and the possibility of carrying animal source genetic viruses is avoided. According to the method, the 3alpha reductase is used, the characteristic of high specificity of the enzyme is utilized, the selective reduction effect is good, and no 3beta hydroxyl isomer exists; meanwhile, the process is safe and environmentally friendly through reaction of alkaline water and the glycerin/2-methyltetrahydrofuran system, and the compound II is high in yield and good in purity.

Description

technical field [0001] The invention belongs to the technical field of organic chemical synthesis / drug synthesis, and in particular relates to a preparation method of plant source 7-ketolithocholic acid. Background technique [0002] The chemical formula of 7-ketolithocholic acid (3α-hydroxy 7-keto-5β-cholestane-24-acid) is C 24 h 38 o 4 , its structural formula is as follows: [0003] [0004] 7-Ketolithocholic acid is an important pharmaceutical intermediate, which is the main ingredient for the preparation of various cholic acid drugs such as chenodeoxycholic acid, ursodeoxycholic acid, obeticholic acid, tauroursodeoxycholic acid, etc. Starting materials. [0005] Ursodeoxycholic acid is an important hepatobiliary drug. It has clear curative effect on gallbladder cholesterol stones, cholestatic liver disease, bile reflux gastritis and other hepatobiliary diseases. The ancient preparation method of ursodeoxycholic acid mainly Extracted from bear bile. In recent yea...

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): C07J9/00
CPCC07J9/005Y02P20/55
Inventor 李斌曾春玲龙能吟谢来宾戴怡才
Owner HUNAN KEREY BIOTECH
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