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

Synthesis method of chiral amine

A synthesis method and technology of chiral amines, applied in the field of chiral amine synthesis, can solve the problems of harsh reaction conditions and high cost

Active Publication Date: 2021-06-18
ASYMCHEM LAB TIANJIN +1
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The main purpose of the present invention is to provide a kind of synthetic method of chiral amine compound, to solve the problem of high cost and harsh reaction conditions of the synthetic method of chiral amine compound in the prior art

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
  • Synthesis method of chiral amine
  • Synthesis method of chiral amine
  • Synthesis method of chiral amine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1 Screening of wild-type amino enzymes

[0054] This embodiment first chooses to Chromobaterium Violaceum The transaminase (sequence such as SEQID NO: 1, which is recorded as a CVTA wild type aminotransferase), the catalytic activity of the substrate (substrate 1) which catalyzes the primary resistance of the synthesis of the target is tested. Among them, the detailed process of the CVTA wild-type amino enzyme catalytic substrate 1 is as follows: 1 ml system includes 1 mg substrate 1, 0.1 mg PLP, 1 mg isopropylamine hydrochloride, 50 mg enzyme powder, pH 8.0 100 mm phosphate buffer Liquid, 30 o C reaction 40 h.

[0055] The results show that the efficiency of the CVTA wild-type amino enzyme catalytic synthetic substrate 1 is 0.56%.

[0056] Next, it is selected that the same but different kinds of the above CVTA wild-type aminaminase, and the amino acid sequence is selected from the SEQ IDNO: 1, and the homology is from 82% of the wild-type aminaminase (specifically...

Embodiment 2

[0062] In addition to the transaminase from the Chromobacterium source, this application also tested other stems of 69% to 87% homology with ChromOBATERIUMVIOLACEUM. The specific information is shown in Table 2.

[0063] The wild-type aminotransferase of different sources in this embodiment, the amino acid sequence between the 54th and 63th and the 96th and the 96th, also shows highly conservative. These wild-type transaminases have been tested to have a catalytic activity of 0.01% to 1% for the target large-site resistant substrate (substrate 1) (see Table 2).

[0064] Table 2: With CHROMOBATERIUM VIOLACEUM, it has lower homology, but derived from other transaminase.

[0065]

[0066] .

[0067] In the above table, + represents the conversion rate of 0.01% to 0.1%, ++ represents between 0.1 to 0.5%, ++ + represents the conversion rate of 0.5 ~ 1%.

[0068] Further, the sequence alignment is performed on the different aminaminase strains shown in Tables 1 and 2, and the compar...

Embodiment 3

[0070] In order to further confirm that the impact of the aminotransferase of the above conservative amino acid region, the inventor is preliminary Chromobaterium Violaceum The conservative amino acid region 1 in the source of the source of transaminase (ie, SEQ ID NO: 1) (specific sequence is DGMAGL) WC The amino acid W and C in VnVGYGR were mutated, and the catalytic efficiency of these conserved amino acids had improved after mutation of these conservative amino acids, and the conversion rate after WA mutation was increased between 5 and 10%, and CA mutation The conversion rate is increased to between 1 to 5% (the specific reaction process is described in Example 1).

[0071] In order to confirm the source of transaminase from other species, the conversion of the substrate has increased after the conserved site, and the inventors also have the same mutation of other sources of transaminase, and the test results are shown below.

[0072] table 3:

[0073] .

[0074] In the abo...

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 provides a synthesis method of a chiral amine compound. According to the synthesis method, transaminase is adopted to carry out transamino reaction on a ketone substrate shown in a formula I under the action of an amino donor, and a chiral amine compound is obtained. The transaminase in the formula I is a kind of transaminase with a conservative amino acid sequence region, the conservative amino acid sequence region at least comprises a region 1 and a region 2, the conservative amino acid sequence of the region 1 is MAGLWCVN, and the conservative amino acid sequence of the region 2 is YNTFFKT. The large steric hindrance chiral amine is synthesized by adopting transaminase with a specific conservative amino acid sequence region, the enzyme catalysis reaction volume is small, the synthesis route is short, the product yield is high, high-cost noble metal catalysis is not needed for synthesis conditions, three wastes are greatly reduced, and the production cost is saved.

Description

Technical field [0001] The present invention relates to the field of chiral amine synthesis, and in particular, a method of synthesizing a chiral amine. Background technique [0002] A large-scale obstructive amine compound (the group refers to the group next to the potential chiral carbonyl group than the methyl large) is a class of extensive applications in optical active substances, functional molecules, drugs, and ligand synthesis. Chiral intermediate. However, there is less related reports in such chiral compounds, and unable to achieve satisfactory results. For example, the selectivity of the lactabhenyl tert-butyl group is 76% (Angew. Chem. Int. ED. 2007, 46, 4367). At present, an asymmetrical hydrogenation of a small resistance (a class of a compound of the group is h or methyl), some metal catalysts, such as ruthenium, ruthenium, and palladium, are reported. Good stereo selectivity, but the catalytic effect becomes poor as the carbonyl is large. [0003] Asymmetric hydro...

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): C12P13/00C12P17/12C12P17/14C12N9/10
CPCC12P13/001C12P17/12C12P17/14C12N9/1096C12Y206/01C12R2001/01
Inventor 洪浩詹姆斯·盖吉肖毅张娜焦学成马玉磊牟慧艳王祖建孙凯华贾如刘芳刘文敬
Owner ASYMCHEM LAB TIANJIN
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