Synthesis method of amino-protecting glycine dipeptidase derivant

A technology of glycine dipeptide and fluorenylmethoxycarbonyl glycine dipeptide, which is applied in the direction of peptides, etc., can solve the problems that product separation is not suitable for large-scale production, product yield and purity are low, and achieve the effect of environmental friendliness and simple process operation

Inactive Publication Date: 2010-02-24
上海力智生化科技有限公司
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  • Abstract
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Problems solved by technology

[0004] 9-fluorenylmethyloxycarbonyl (Fmoc-) and tert-butoxycarbonyl have been reported in the relevant professional literature, but the ubiquitous problem is that the yield (<80%) and purity (content<95%) of the product are relatively high Low, and post-treatment and product separation are not suitable for large-scale production

Method used

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  • Synthesis method of amino-protecting glycine dipeptidase derivant

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Experimental program
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Embodiment 1

[0025] Dissolve 6.1 grams (0.050 moles) of glycine dipeptide in 63 mL of 10% sodium carbonate solution, stir to dissolve the glycine dipeptide, and add dropwise Fmoc-ONSu (16.8 grams, 0.05 mol) solution, the dropwise addition was completed in 30 minutes. After the dropwise addition, the reaction was stirred at 30° C. for 2 hours, diluted with about 50 mL of water, and the reaction solution was extracted with toluene (80 mL), and the resulting aqueous phase was acidified to pH = 2, and then extracted with ethyl acetate (100 mL), the obtained organic phase was washed with water, and the organic phase was concentrated to remove the ethyl acetate solvent, and a white solid was precipitated. After filtering and drying, 16.1 g of the product Fmoc-Gly-Gly-OH was obtained, with a yield of 91%.

Embodiment 2

[0027] Dissolve 6.1 grams (0.05 moles) of glycine dipeptide in 79 mL of 10% potassium carbonate solution, stir to dissolve the glycine dipeptide, and add dropwise Fmoc-ONSu (17.7 grams, 0.0525 mol) solution, the dropwise addition was completed in 30 minutes. After the dropwise addition, the reaction was stirred at 30° C. for 2 hours, diluted with about 50 mL of water, and the reaction solution was extracted with toluene (80 mL), and the resulting aqueous phase was acidified to pH = 2, and then extracted with ethyl acetate (100 mL), the obtained organic phase was washed with water, and the organic phase was concentrated to remove the ethyl acetate solvent, and a white solid was precipitated. After filtering and drying, 16.5 g of the product Fmoc-Gly-Gly-OH was obtained, with a yield of 93%.

Embodiment 3

[0029] Dissolve 6.1 g (0.050 moles) of glycine dipeptide in 63 mL of 10% sodium carbonate solution, stir to dissolve the glycine dipeptide, and add Boc dissolved in methanol (60 mL) dropwise at 20°C 2 O (10.9 g, 0.05 mol) solution, the dropwise addition was completed in 30 minutes. After the dropwise addition was completed, the reaction was stirred at 30° C. for 2 hours, and the reaction solution was extracted with methyl tert-butyl ether (80 mL). Acidify with hydrochloric acid to pH = 3, and then extract with ethyl acetate (100 mL). The obtained organic phase is washed with water, and then the organic phase is concentrated to remove the ethyl acetate solvent, and a white solid is precipitated. After filtering and drying, 9.29 g of the product Boc-Gly-Gly-OH was obtained, with a yield of 80%.

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Abstract

The invention relates to a synthesis method of amino-protecting glycine dipeptidase derivant. The amino-protecting glycine dipeptidase derivant is N-9-Fmoc glycine dipeptidase, N-Boc glycine dipeptidase and N-acetyl glycine dipeptidase. The invention has the technology that glycine dipeptidase is dissolved in 1-20% of inorganic aqueous alkali, and the organic solution of Fmoc-OSu or Boc2O or Ac2Ois dropwise added; reaction is finished within 1-12 hours, the yield of the product Fmoc-Gly-Gly-OH, Boc-Gly-Gly-OH and Ac-Gly-Gly-OH is between 80-95%, and the content of the product is above 99%. The invention has simple technology, easy industrialization and low cost. The product of the invention is the important raw material for synthesizing polypeptide compound.

Description

technical field [0001] The invention relates to a synthesis method of amino-protected glycine dipeptide derivatives. Background technique [0002] Amino-protected glycine dipeptide (P-Gly-Gly-OH) is an important intermediate of peptide biofine products in the synthesis of peptide drugs. 9-fluorenylmethoxycarbonyl (Fmoc-) is a basic sensitive protecting group, tert-butoxycarbonyl (Boc-) is an acid sensitive protecting group, and acetyl (Ac-) is more stable to acid and alkali than the first two protecting groups , can only be deprotected under strong acid-base conditions. This different property to acid and base makes the glycine dipeptide protected by these three groups widely used in peptide synthesis. Therefore, it is particularly important to develop the synthesis process of the glycine dipeptide derivatives protected by these three groups. [0003] Prior Art US Patent US20020098567 develops the reaction of glycine dipeptide with equimolar sodium bicarbonate and acetic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/062C07K1/06
Inventor 唐晓华刘锡玲
Owner 上海力智生化科技有限公司
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