Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of solid-liquid synthesis method of buserelin

A technology of solid-liquid synthesis and solid-phase synthesis, which is applied in the field of solid-liquid synthesis of buserelin, can solve the problems of easy introduction of heavy metals into products, unfavorable industrial production, and high operation requirements, so as to reduce special equipment requirements, improve synthesis efficiency, The effect of safe and easy operation

Active Publication Date: 2017-11-14
NANTONG SHIMEIKANG PHARMA CHEM
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Catalytic hydrogenation is to use Pd / C, the method of passing hydrogen to remove the protective group, Pd / C is expensive, the product is easy to introduce heavy metals, the necessary heavy metal detection is required, it is not suitable for the production of drugs, and catalytic hydrogenation requires special equipment, operating requirements High, low safety factor, not conducive to industrial production

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 kind of solid-liquid synthesis method of buserelin
  • A kind of solid-liquid synthesis method of buserelin
  • A kind of solid-liquid synthesis method of buserelin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1: Preparation of Fmoc-Tyr(tBu)-dichlorotrityl chloride resin.

[0031]Weigh 0.5g (0.30mmol) of dichlorotrityl chloride resin (substitution value 0.60mmol / g) into a 20ml BD syringe (or common glass peptide reactor) with a sieve plate, and swell with 3 times the volume of the resin in DCM Twice, 1 hour each time, to make the resin swell completely. Dissolve 551.40mg (1.2mmol) Fmoc-Tyr(tBu)-OH in 10ml DMF, add 0.4ml (2.4mmol) DIEA, activate for 3min, add the mixed solution into the solid phase reactor, stir for 2h, wash with DMF three times, Wash three times with DCM. Add 10 ml of DCM and 800 μl of methanol-blocked resin, stir for 30 min, wash with DCM for 3 times, and drain to obtain Fmoc-Tyr(tBu)-dichlorotrityl chloride resin.

Embodiment 2

[0032] Example 2: Synthesis of Pyr-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-dichlorotrityl chloride resin.

[0033] Fmoc-Tyr (tBu)-dichlorotrityl chloride resin is loaded into a solid-phase reactor, washed twice with DMF, and the Fmoc protecting group is removed twice with 20% (v / v) piperidine / DMF solution, and the time is 5min and 20min respectively, washed 3 times with DMF, and tested by ninhydrin method. Dissolve 460.08mg (1.2mmol) Fmoc-Ser(tBu)-OH and 162.12mg (1.2mmol) HOBt in 10ml DMF, ice bath for 10min, add 0.4ml (2.4mmol) DIEA, activate for 3min, then add 455.04mg (1.2mmol) ) HBTU, the mixed solution was added to the solid-phase reactor, stirred for 1.5h, and the ninhydrin test was negative, washed three times with DMF and three times with DCM.

[0034] Repeat the above operation, connect Fmoc-Trp(Boc)-OH, Fmoc-His(Trt)-OH, H-Pyr-OH in sequence, the amount of raw materials: amino acid (1.2mmol), HBTU 455.04mg (1.2mmol), HOBt 162.12mg (1.2 mmol). Example 3: Synthesis of ...

Embodiment 3

[0034] Repeat the above operation, connect Fmoc-Trp(Boc)-OH, Fmoc-His(Trt)-OH, H-Pyr-OH in sequence, the amount of raw materials: amino acid (1.2mmol), HBTU 455.04mg (1.2mmol), HOBt 162.12mg (1.2 mmol). Example 3: Synthesis of Fmoc-D-Ser(tBu)-Leu-Arg(HCl)-dichlorotrityl chloride resin.

[0035] Weigh 0.5g (0.30mmol) of dichlorotrityl chloride resin (substitution value 0.60mmol / g) into a 20ml BD syringe (or common glass peptide reactor) with a sieve plate, and swell with 3 times the volume of the resin in DCM Twice, 1 hour each time, to make the resin swell completely. Dissolve 519.48mg (1.2mmol) Fmoc-Arg(HCl)-OH in 10ml DMF, add 0.4ml (2.4mmol) DIEA, activate for 3min, add the mixed solution into the solid phase reactor, stir for 2h, wash with DMF three times, Wash three times with DCM. Add 10 ml of DCM and 800 μl of methanol-blocked resin, stir for 30 min, wash with DCM for 3 times, and drain to obtain Fmoc-Arg(HCl)-dichlorotrityl chloride resin.

[0036] The Fmoc-Arg (HC...

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 solid-liquid synthesis method of buserelin, comprising the following steps: 1) synthesizing the pentapeptide fragment H-Pyr-His-Trp-Ser-Tyr-OH with a solid-phase synthesis method, 2) using a solid-phase The synthesis method synthesizes the tripeptide fragment H-D-Ser(tBu)-Leu-Arg(HCl)-OH, and then the liquid phase synthesis method connects the special amino acid Pro-NHEt·HCl to synthesize the 4-peptide fragment H-D-Ser(tBu)- Leu-Arg(HCl)-Pro-NHEt; 3) Pentapeptide fragments and tetrapeptide fragments are condensed in liquid phase, and after precipitation, purification, desalting, and salt conversion, buserelin is obtained. The invention has simple process steps, mild reaction conditions, easy control, little harm to human body and environment, high yield and is suitable for large-scale production.

Description

technical field [0001] The invention relates to a solid-liquid synthesis method of buserelin. Background technique [0002] Buserelin (Buserelin), trade name is CinnaFact, and the Buserelin acetate aqueous injection produced by CinnaGen Company has been put into the market. Indications: For the treatment of endometriosis, central precocious puberty, breast and prostate cancer. Buserelin is a gonadotropin-releasing hormone (LH-RH) drug. LH-RH is a hormone secreted by the hypothalamus, which can promote the synthesis of pituitary gland and release luteinizing hormone and egg cell estrogen. Homologues of this class of hormones include Goserelin, Leuprorelin, Triptorelin, and Gonadoerlin. [0003] Buserelin is a linear nonapeptide with a molecular weight of 1239.42, a CAS registration number of 57982-77-1, and a molecular formula of C 60 h 86 N 16 o 13 , whose amino acid sequence is H-Pyr-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NHEt. The structural formula is as follows: ...

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): C07K7/23C07K1/10C07K1/06C07K1/04C07K1/02
Inventor 董守良玄其存曹硕常民
Owner NANTONG SHIMEIKANG PHARMA CHEM