Preparation method of argireline

A technology of guanidinium and amino resins, which is applied in the field of preparation of ajirelin, which can solve the problems of unfavorable promotion and use, high cost of ajirelin, and cumbersome steps

Active Publication Date: 2014-04-02
浙江华军药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This preparation method steps are loaded down with trivial details, and yield is low, and because ajirelin peptide chain is shorter, use fragment synthesis method to inevitably cause a large amount of waste of fragment, these all cause the cost of ajirelin to be higher, are unfavorable for its popularization and production. use

Method used

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  • Preparation method of argireline
  • Preparation method of argireline
  • Preparation method of argireline

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preparation example Construction

[0110] The invention discloses a preparation method of ajirelin. Those skilled in the art can refer to the content herein to obtain ajirelin. In particular, it should be pointed out that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The preparation method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously make changes or appropriate changes and combinations to the preparation method and application herein without departing from the content, spirit and scope of the present invention to realize and Apply the technology of the present invention.

[0111] The reagents and raw materials used in the preparation method of ajirelin provided by the present invention can be purchased from the market.

[0112] See Table 1 for the Chinese-English comparison of English abbreviations involved in the present...

Embodiment 1

[0115] The preparation of embodiment 1 amino resin

[0116] Weigh 10 g of Rink Amide-MBHA Resin (purchased from Shangyu Puer Resin Co., Ltd.), with a substitution degree of 0.5 mmol / g, add 100 mL of DMF to the resin, stir and wash for 10 minutes, remove the DMF by suction filtration on the No. 3 sand core, and then add 80 mL of DCM was fully swollen for 1 hour.

[0117] Add 80mL of 25% by volume hexahydropyridine DMF solution into the above-mentioned fully swollen Rink Amide-MBHA Resin, react at 25°C for 20 minutes, filter under reduced pressure on the No. 3 sand core, and use 80mL DMF and 80mL DCM alternately Washed six times in total to obtain the amino resin.

Embodiment 2

[0118] The preparation of the first amino acid resin of embodiment 2

[0119] Take Fmoc-L-ArgfPbf)-OH15mmol, HOBT20mmol, DIEA30mmol, dissolve it with 50mL of DMF, add it to the amino resin prepared in Example 1 and stir, and when it is cooled to -15°C, slowly add EDCI30mmol dropwise with a pipette funnel, The dropwise addition was completed in half an hour. After stirring at -15°C for half an hour, let it naturally return to 20°C and react for one hour. Take a few resins for ninhydrin negative test. The resin is colorless and transparent, and the reaction is complete. The No. 3 sand core was vacuum-filtered to remove the reaction solution, and the resin was washed once with 80mL DMF and 80mL DCM. Add 80mL of 25% hexahydropyridine DMF solution by volume to the obtained resin, react at 25°C for 20 minutes, filter under reduced pressure on No. The first amino acid resin.

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Abstract

The invention belongs to the technical field of medicinal chemistry and discloses a preparation method of argireline. The preparation method provided by the invention comprises the steps: activating resin to obtain amino resin; gradually enabling the obtained amino resin, guanidyl-protected L-arginine, the other guanidyl-protected L-arginine and side chain amino protected L-glutamine to be subjected to the first coupling reaction to obtain tripeptide resin; gradually enabling the obtained tripeptide resin, L-methionine, side chain carboxyl protected L-glutamic acid and side chain carboxyl protected N-acetyl-L-glutamic acid to be subjected to second coupling reaction to obtain hexapeptide resin; cracking the obtained hexapeptide resin to obtain a first product; and purifying the obtained first product to obtain the argireline. The preparation method provided by the invention is used for preparing the argireline through solid-phase synthesis so as to be simple in operation, capable of remarkably increasing the yield of the argireline and greatly improving the purity of the argireline, suitable for large-scale industrial production and more beneficial to the popularization and application of the argireline.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, in particular to a preparation method of ajirelin. Background technique [0002] Argireline, also known as acetyl hexapeptide-3 and botulinum toxin, is derived from the N-terminal region of SNAP-25 protein (25kDa synaptosome-associated protein), consisting of six amino acids Residue composition, the molecular formula is C 34 h 60 N 14 o 12 S, molecular weight 888.4, it has the structure shown in formula I, [0003] [0004] Ajirelin participates in the competition for the site of SNAP-25 in the fusion complex, thereby affecting the formation of the fusion complex, causing the vesicles to fail to release neurotransmitters effectively, weakening muscle contraction, and then relaxing muscles and soothing fine lines It can make the skin appear clear and flawless, and can also promote cell regeneration and restore the softness and elasticity of the skin, so it is widely used in the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C07K1/20C07K1/06C07K1/04
Inventor 顾含华俞保彬周天琼
Owner 浙江华军药业有限公司
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