A method for preparing leuprolide by combining solid phase and liquid phase

A technology of leuprorelin and liquid phase is applied in the field of preparing leuprolide by combining solid phase and liquid phase, which can solve problems such as difficulty in large-scale production and inconvenience, achieve high synthesis yield and avoid product instability. Effect

Active Publication Date: 2022-03-29
浙江湃肽生物股份有限公司南京分公司
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the synthesis of leuprolide by the existing solid-phase synthesis method, after connecting all amino acids from the carbon end, the liquid ethylamine is used to cut it from the resin. However, the cutting with liquid ethylamine needs to be carried out at low temperature and under pressure. Inconvenient in industrial production, difficult to produce on a large scale

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 method for preparing leuprolide by combining solid phase and liquid phase
  • A method for preparing leuprolide by combining solid phase and liquid phase
  • A method for preparing leuprolide by combining solid phase and liquid phase

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] A method for preparing leuprolide by combining solid phase and liquid phase,

[0079] Preparation of the liquid phase carrier: Add potassium carbonate to DMF, then add 3-ethoxy-4-hydroxybenzaldehyde and 2-(2-ethoxyphenoxy)bromoethane, protect with nitrogen, at 70°C Stir the reaction for 24 h at a temperature of 100 °C, add deionized water to precipitate, filter, wash, and dry to obtain benzaldehyde compounds; under nitrogen protection, add benzaldehyde compounds to the tetrahydrofuran solution, add sodium borohydride, The reaction was stirred at high temperature for 6 h. After the reaction was completed, deionized water was added to the solution to precipitate a precipitate, which was filtered, washed, and dried to obtain a liquid phase carrier. The usage amount of potassium carbonate is 1.2 wt% of DMF, the addition amount of 3-ethoxy-4-hydroxybenzaldehyde is 6 wt% of DMF, the addition of 2-(2-ethoxyphenoxy)bromoethane The amount is 9 wt% of DMF, the tetrahydrofuran so...

Embodiment 2

[0094] A method for preparing leuprolide by combining solid phase and liquid phase,

[0095] Preparation of the liquid phase carrier: Add potassium carbonate to DMF, then add 3-ethoxy-4-hydroxybenzaldehyde and 2-(2-ethoxyphenoxy)bromoethane, protect with nitrogen, at 70°C Stir the reaction for 24 h at a temperature of 100 °C, add deionized water to precipitate, filter, wash, and dry to obtain benzaldehyde compounds; under nitrogen protection, add benzaldehyde compounds into the tetrahydrofuran solution, add sodium borohydride, The reaction was stirred at high temperature for 6 h. After the reaction was completed, deionized water was added to the solution to precipitate a precipitate, which was filtered, washed, and dried to obtain a liquid phase carrier. The usage amount of potassium carbonate is 1.2 wt% of DMF, the addition amount of 3-ethoxy-4-hydroxybenzaldehyde is 6 wt% of DMF, the addition of 2-(2-ethoxyphenoxy)bromoethane The amount is 9 wt% of DMF, the tetrahydrofuran ...

Embodiment 3

[0110] A method for preparing leuprolide by combining solid phase and liquid phase,

[0111] Compared with Example 2, the present embodiment is only different in that in the preparation of Fmoc-Arg(Pbf)-Pro-Wang resin, the usage amount of 2-[(3-aminophenyl)sulfonyl)ethanol is DMF 1.9 wt%.

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 a method for preparing leuprolide by combining a solid phase and a liquid phase, which belongs to the technical field of polypeptide synthesis, and specifically relates to a liquid phase carrier and its application. Hydroxybenzaldehyde and 2-(2-ethoxyphenoxy)bromoethane react in DMF containing potassium carbonate to obtain a liquid phase carrier, and the above-mentioned liquid phase carrier is used to carry out fragment synthesis in the liquid phase; the fragment synthesis obtains Fmoc‑Arg‑Pro‑O‑liquid phase carrier; the product of the above steps is removed from the liquid phase carrier, combined with a solid phase resin, and then coupled with amino acid reagents in the order of the amino acid sequence in leuprolide to obtain leuprolide The leuprolide-based polypeptide resin; after cutting the leuprolide-based polypeptide resin, the leuprolide-based polypeptide is separated, and then ethylaminated to obtain the leuprolide.

Description

technical field [0001] The invention belongs to the technical field of polypeptide synthesis, and in particular relates to a method for preparing leuprolide by combining a solid phase and a liquid phase. Background technique [0002] Leuprolide is a gonadotropin-releasing hormone analog that is widely used to treat women with precocious puberty, endometriosis, uterine fibroids, or premenopausal breast cancer and men with prostate cancer. The chemical name of leuprolide is 5-oxo-prolyl-histidyl-tryptophanyl-seryl-tyrosyl-D-leucyl-leucyl-arginyl-N-acetyl Base-prolinamide, peptide sequence: H-Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NH-C 2 h 5 , molecular weight 1209.41. In the synthesis of leuprolide by the existing solid-phase synthesis method, after connecting all amino acids from the carbon end, the liquid ethylamine is used to cut it from the resin. However, the cutting with liquid ethylamine needs to be carried out at low temperature and under pressure. It is inconvenien...

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 Patents(China)
IPC IPC(8): C07K7/23C07K1/16C07K1/06C07K1/04C07K1/02
CPCC07K7/23
Inventor 章砚东涂仕前魏祝宇潘海良
Owner 浙江湃肽生物股份有限公司南京分公司
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