Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Acinetobacter sp. ZJPH1806 and application thereof to preparation of miconazole chiral intermediate

A technology of bacillus and wet bacteria, which is applied in the field of preparation of miconazole chiral intermediates, can solve the problems of environmental pollution and low yield, and achieve the effect of high optical purity

Active Publication Date: 2019-07-16
ZHEJIANG UNIV OF TECH
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The preparation of (R)-2-chloro-1-(2,4-chlorophenyl)ethanol by chemical method requires the use of complexes of chiral oxazoboridine and heavy metal ruthenium as a catalyst, which will pollute the environment and reduce the yield. not tall

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
  • Acinetobacter sp. ZJPH1806 and application thereof to preparation of miconazole chiral intermediate
  • Acinetobacter sp. ZJPH1806 and application thereof to preparation of miconazole chiral intermediate
  • Acinetobacter sp. ZJPH1806 and application thereof to preparation of miconazole chiral intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1, screening and identification of Acinetobacter ZJPH1806 strain

[0037] 1. Strain screening

[0038] 1) Enrichment culture and primary screening: Add 1g of fresh soil samples collected near the Jianfeng Mountain Orchard in Wucheng District, Jinhua City, Zhejiang Province, into a 250mL shake flask filled with 50mL enrichment medium, culture at 30°C and 200rpm for 5 days , transfer 1 mL of the culture solution to a fresh enrichment medium, continue the enrichment culture for 5 days, and repeat the enrichment twice. The enrichment medium consists of: (NH 4 ) 2 SO 4 2g / L, KH 2 PO 4 2g / L, NaCl1g / L, MgSO 4 ·7H 2 O 0.5g / L, 2,2',4'-trichloroacetophenone (2g / L) is the only carbon source, the solvent is water, pH 6.5.

[0039] 2) Plate culture: Dilute the enriched culture solution with normal saline for 10 4 -10 6 After doubling, it was spread on a plate containing screening medium, cultured at 30°C for 2 days, and a single colony strain was obtained after...

Embodiment 2

[0060] Embodiment 2 optimizes medium composition

[0061] 1. Optimize the types of carbon sources, nitrogen sources and inorganic salts in the fermentation medium

[0062] Fermentation medium composition: carbon source 15g / L, nitrogen source nitrogen content 1.8g / L, inorganic salt 1mM, solvent is water, pH 6.5.

[0063] Acinetobacter ZJPH1806 was inoculated into fermentation media composed of different carbon sources, nitrogen sources and inorganic salts. The culture conditions were as follows: initial pH value 6.5, shake flask filling volume 100mL / 250mL Erlenmeyer flask, culture temperature 30°C, shaker The rotating speed is 200rpm, the inoculum volume is 10%, and the incubation time is 24h. The enzyme activity and ee value are determined by the method in Example 1.

[0064] By examining the single factor experiments (shown in Table 1-Table 3 and Table 5) of different types of carbon sources, nitrogen sources and inorganic salts, the best carbon sources, nitrogen sources and...

Embodiment 3

[0087] Embodiment 3: the acquisition of wet fungus cells

[0088] (1) Incline culture: Acinetobacter ZJPH1806 was inoculated into the slant medium, cultured in a constant temperature incubator at 30°C for 1-2 days to obtain slant strains, and stored in a refrigerator at 4°C. The final concentration of the slant medium consists of: glucose 15g / L, peptone 7.5g / L, yeast extract 6g / L, (NH 4 ) 2 SO 4 3g / L, KH 2 PO 4 1.5g / L, NaCl 0.75g / L, MgSO 4 ·7H 2 O 0.75g / L, agar powder 20g / L, solvent is water, pH 6.5.

[0089] (2) Seed culture: Inoculate the slant bacteria into the seed medium, cultivate at 30°C and 200rpm for 12 hours, and obtain the seed liquid; the composition of the seed medium is: glucose 15g / L, peptone 20g / L, yeast extract 10g / L, (NH 4 ) 2 SO 4 2g / L, KH 2 PO 4 2g / L, NaCl1g / L, MgSO 4 ·7H 2 O 0.5g / L, solvent is water, pH 6.5.

[0090] (3) Fermentation culture: transfer the seed liquid to the fermentation medium with an inoculum size of 10% (v / v), culture a...

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

The invention discloses acinetobacter sp. ZJPH1806 and an application thereof to preparation of a miconazole chiral intermediate. 2,2',4'-trichloroacetophenone is subjected to asymmetric reduction toprepare (R)-2-chlorine-1-(2,4-chlorophenyl) ethanol, and obtained products are high in optical purity. In a phosphate buffer liquid system of which the pH is 7.6, glycerine is used as an auxiliary substrate, 2g / L of a substrate is added, a reaction is performed for 26h, the yield of R-type products is 83.2%, and e.e. value is greater than 99.9%.

Description

[0001] (1) Technical field [0002] The invention relates to the preparation of a chiral intermediate of miconazole, in particular to a method for asymmetrically synthesizing the chiral intermediate of miconazole by utilizing a new bacterial strain-Acinetobacter ZJPH1806 biocatalysis. [0003] (2) Background technology [0004] 2-Chloro-1-(2,4-dichlorophenyl)ethanol (molecular weight: 225.48, CAS number: 11446-57-0) is a key chiral intermediate for the preparation of miconazole. Among them, the R-configuration compound, that is, the formula (I-a) is the key chiral intermediate for the preparation of miconazole mentioned in the present invention. The chemical name of formula (Ⅲ) is 1-[2-(2,4-dichlorophenyl)-2-[(2,4-dichlorophenyl)methoxy]ethyl]-1H-imidazole, also It is called diclobendazole. [0005] [0006] Formula (I) is 2,2',4'-trichloroacetophenone, formula (II) is 2-chloro-1-(2,4-chlorophenyl)ethanol, and formula (III) is miconazole. [0007] [0008] Formula (I-a...

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): C12N1/20C12P7/22C12R1/01
CPCC12N1/20C12P7/22C12N1/205C12R2001/01
Inventor 王普缪彦斐刘月旺
Owner ZHEJIANG UNIV OF TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com