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

Synthetic method for goserelin

A synthesis method and the technology of desirelin, applied in the field of chemical pharmacy, can solve the problems of high pollution of three wastes and low yield of peptides, and achieve the effect of simplifying cumbersomeness, avoiding unsafe cutting, and shortening synthesis time.

Inactive Publication Date: 2014-08-27
ANHUI RUBIOX VISION BIOTECH
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In order to solve the technical problems of low yield of deserelin synthesis and high pollution of three wastes in the prior art, the present invention provides a synthesis method of deserelin, and the technical scheme adopted is as follows:

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
  • Synthetic method for goserelin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] 1. Preparation of Fmoc-Pro-CTC resin

[0034] The preparation of Fmoc-Pro-CTC resin is carried out according to the following steps:

[0035] 1). Take 1g of CTC resin (Loading: 1.2mmol / g, 1.2mmol), soak it in 15ml of DCM to fully swell the resin;

[0036] 2). Take 0.607g Fmoc-Pro-OH (FW:337.4, 1.8mmol), dissolve it with 15ml of peptide reagent, add it to the reactor, and react at room temperature for 1.5 hours;

[0037] 3) Blow dry, wash with DMF and methanol three times respectively, and blow dry.

[0038] 2. Linkage of Deserelin Amino Acids

[0039] 2.1 Preparation of Fmoc-Arg(pbf)-Pro-CTC resin

[0040] 1). Add 15ml of deprotection reagent, react at room temperature for 15 minutes, dry, wash with DMF and methanol 3 times, dry,

[0041] 2) Take 2.4g Fmoc-Arg(pbf)-OH (FW: 648.8, 3.6mmol), 1.2gTBTU (FW: 321, 3.6mmol), 0.5gHOBT (FW: 135, 3.6mmol), dissolve it with 15ml peptide reagent, Add to the reactor, react at room temperature for 1.5h,

[0042] 3) Blow dry, wa...

Embodiment 2

[0078] 1. Preparation of Fmoc-Pro-CTC resin

[0079] The preparation of Fmoc-Pro-CTC resin is carried out according to the following steps:

[0080] 1). Take 10g of CTC resin (Loading: 1.2mmol / g, 12mmol), soak it in 100ml of DCM to fully swell the resin;

[0081] 2). Take 6.1g of Fmoc-Pro-OH (FW: 337.4, 18mmol), dissolve it with 100ml of peptide reagent, add it to the reactor, and react at room temperature for 1.5 hours;

[0082] 3) Blow dry, wash with DMF and methanol three times respectively, and blow dry.

[0083] 2. Linkage of Deserelin Amino Acids

[0084] 2.1 Preparation of Fmoc-Arg(pbf)-Pro-CTC resin

[0085] 1) Add 100ml of deprotection reagent, react at room temperature for 15 minutes, dry, wash with DMF and methanol 3 times, and dry;

[0086] 2) Take 23.3g Fmoc-Arg(pbf)-OH (FW: 648.8, 36mmol), 11.6gTBTU (FW: 321, 36mmol), 4.8 HOBT (FW: 135, 36mmol), dissolve it with 100ml peptide reagent, and add it to the reactor. Reaction at room temperature for 1.5h;

[0087...

Embodiment 3

[0123] 1. Preparation of Fmoc-Pro-CTC resin

[0124] The preparation of Fmoc-Pro-CTC resin is carried out according to the following steps:

[0125] 1). Take 150g of CTC resin (Loading: 1.2mmol / g, 180mmol), soak it in 1000ml of DCM to fully swell the resin;

[0126] 2). Take 91.1g Fmoc-Pro-OH (FW: 337.4, 270mmol), dissolve it with 1000ml peptide reagent, add it to the reactor, and react at room temperature for 1.5 hours;

[0127] 3) Blow dry, wash with DMF and methanol three times respectively, and blow dry.

[0128] 2. Linkage of Deserelin Amino Acids

[0129] 2.1 Preparation of Fmoc-Arg(pbf)-Pro-CTC resin

[0130] 1). Add 1000ml deprotection reagent, react at room temperature for 15 minutes, dry, wash with DMF and methanol 3 times, and dry;

[0131] 2) Take 350.1g Fmoc-Arg(pbf)-OH (FW: 648.8, 540mmol), 173.4g TBTU (FW: 321, 540mmol), 72.9 HOBT (FW: 135, 540mmol), dissolve it with 1000ml of peptide reagent, and add it to the reactor , react at room temperature for 1.5h; ...

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 synthetic method for goserelin and belongs to the technical field of chemical pharmacy. The synthetic method comprises: taking 2-chlorotritylchloride polymer resin as a raw material, linking 2-chlorotritylchloride polymer resin with carboxyl of fluorenylmethyloxycarbonyl-protected proline under an alkaline condition, so as to obtain fluorenylmethyloxycarbonyl-protected proline-2-chlorotritylchloride polymer resin, then successively linking with residual amino acids of goserelin through peptide linking connections, using a full-protection cutting reagent for cracking and obtain a full-protection nine-peptide fragment, then performing ethylamination to obtain a full-protection goserelin fragment, and finally cracking the full-protection goserelin fragment to obtain a goserelin crude product. Goserelin is synthesized by employing a solid-liquid combination method and the yield reaches 84.1%. Also, the synthetic method helps to avoid the problems that a pure solid phase is not safe and convenient to cut from resin, the synthetic time is shortened, the tedious process for synthesizing a pure liquid phase is simplified, the production cost is substantially reduced, and the synthetic method is suitable for industrialized popularization.

Description

technical field [0001] The invention relates to a method for synthesizing deserelin, which belongs to the technical field of chemical pharmacy. Background technique [0002] Deserelin is also known as LHRH-Hydrogel implant, RL0903, and its molecular formula is: C 64 h 83 N 17 o 12 , the molecular weight is: 1282.47, the structural formula is as figure 1 shown. Deserelin is a synthetic nonapeptide used in the treatment of central precocious puberty. [0003] Deserelin is a luteinizing hormone-releasing hormone (LHRH) agonist. American scholars Shore et al. reported that for patients with advanced prostate cancer, subcutaneous implantation of deserelin long-acting implants once a year can stably inhibit testosterone for a long time. , to keep it castrated. [0004] The existing synthetic methods all have certain shortcomings. Trifluoroacetic acid is required for each deprotection, so there is a lot of pollution from the three wastes, low peptide yield, and high producti...

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
IPC IPC(8): C07K7/06C07K1/06C07K1/04
Inventor 张旭光汪国兴
Owner ANHUI RUBIOX VISION BIOTECH
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