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Prepartion method of N-acetyl-L-carnosine

A carnosine and acetyl technology, which is applied in the field of synthesis of pharmaceutical intermediates, can solve the problems of complex synthesis process, low yield and purity, and difficulty in industrial application, and achieves the effects of high yield and ideal purity

Active Publication Date: 2011-04-13
SUZHOU FUSHILAI PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The limitation of this method is that special highly active esters need to be prepared, which are currently unavailable in the market, and the synthesis process is complicated, and the production equipment is expensive, so it is not suitable for industrial production.
[0008] Throughout the above-mentioned prior art, due to the lack of commonality of low yield and purity, it is difficult to put it into industrial application

Method used

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  • Prepartion method of N-acetyl-L-carnosine
  • Prepartion method of N-acetyl-L-carnosine
  • Prepartion method of N-acetyl-L-carnosine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Prepare active ester solution (II).

[0021] In a 1000ml reaction flask, add 400g tetrahydrofuran, 84g p-nitrophenol (0.604mol) and 61g triethylamine (0.604mol), lower the temperature to 5°C-10°C, add 47.4g acetyl chloride (0.604mol) dropwise for 30 minutes After the dropwise addition, stir again at a temperature of 5° C. to 10° C. for 0.5 hours. Samples are analyzed by HPLC. The raw material p-nitrophenol is completely reacted, filtered, and the filter cake is washed with 20 g of tetrahydrofuran. After merging the filtrates, 520 g of the active ester solution (solution Containing active ester 109g, molar yield 99.6%) wherein, (II) represents active ester.

[0022]

[0023] Preparation of N-acetyl-L-carnosine (I).

[0024] In a 2000ml reaction flask, add 500g of pure water, 113g of L-carnosine (0.5mol) and 68g of imidazole (1mol), stir to dissolve, cool down to 10°C to 15°C, and dropwise add 520g of active ester solution (II) (the solution contains active Ester 109...

Embodiment 2

[0027] Prepare active ester solution (II).

[0028] In a 1000ml reaction flask, add 400g butanone, 84g p-nitrophenol (0.604mol) and 61g triethylamine (0.604mol), cool down to 5°C-10°C, add dropwise 47.4g acetyl chloride (0.604mol), 30 After 10 minutes of dropwise addition, stir again at a temperature of 5°C to 10°C for 0.5 hours. Samples were analyzed by HPLC. The raw material p-nitrophenol was completely reacted, filtered, and the filter cake was washed with 20g methyl ethyl ketone, and the filtrates were combined to obtain 517g active ester solution. (Containing active ester 108g in the solution, molar yield 99.1%)

[0029] Preparation of N-acetyl-L-carnosine (I).

[0030] In a 2000ml reaction flask, add 500g of pure water, 113g of L-carnosine (0.5mol) and 68g of imidazole (1mol), stir to dissolve, cool down to 10°C to 15°C, and dropwise add 517g of active ester solution (II) (the solution contains active Ester 108g, 0.6mol), 60 minutes dropwise, then stirred at a temperat...

Embodiment 3

[0033] Prepare active ester solution (II).

[0034] In a 1000ml reaction flask, add 400g diethyl ether, 84g p-nitrophenol (0.604mol) and 61g triethylamine (0.604mol), cool down to 5°C-10°C, add dropwise 47.4g acetyl chloride (0.604mol) for 30 minutes After the dropwise addition is completed, stir again at a temperature of 5°C to 10°C for 0.5 hours. Samples are analyzed by HPLC. The p-nitrophenol reaction of the raw material is complete, filtered, and the filter cake is washed with 20g of ether, and the combined filtrates are combined to obtain 505g of active ester solution (solution Containing active ester 108g, molar yield 99.1%)

[0035] Preparation of N-acetyl-L-carnosine (I).

[0036] In a 2000ml reaction flask, add 500g of pure water, 113g of L-carnosine (0.5mol) and 68g of imidazole (1mol), stir to dissolve, cool down to 10°C to 15°C, and dropwise add 505g of active ester solution (II) (the solution contains active Ester 108g, 0.6mol), 60 minutes dropwise, then stirred...

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Abstract

A prepartion method of N-acetyl-L-carnosine, relates to pharmaceutical intermediates synthesis technology field. Dissolving p-nitrophenol into organic solvent, reacting with acetyl chloride to obtain active ester solution at the presence of acid-binding agent; dissolving the L-carnosine and protection agent into water to obtain aqueous solution, then adding the avtive ester solution into the aqueous solution for reacting, and when the reaction is finished, demixing, decoloring the water layer and decompressing condensing to pulpous state, then mixing the condensed residue with acetate acid andadding into polar solvent for stirring, cold separating and drying to obtain the N-acetyl-L-carnosine. The advantages are: the molar yield is more than 90%, the chemical purity is more than 90%, therefore high yield and ideal purity is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of synthesis of pharmaceutical intermediates, in particular to a preparation method of N-acetyl-L-carnosine. Background technique [0002] The English name of N-acetyl-L-carnosine is N-Acetyl-L-Carnosine, the chemical name is acetyl-β-alanyl-histidine (Acetyl-β-Alanyl-Histidine), it is a white crystalline powder, and its structural formula as follows: [0003] [0004] In 1991, Dr. Babizhayev of Russia and Dr. Edoardo Bozzo Costa of Italy and Mr.OvidioCaveri of Bruschettini S.r.l., Genoa began a collaborative research to explore the use of N-acetyl-L-carnosine as an ophthalmic drug. It is a very effective drug for the treatment of senile cataract disease. The clinical application results have promoted the commercial development of N-acetyl-L-carnosine. Many manufacturers have begun to produce and sell N-acetyl-L-carnosine eye drops. In recent years, the global market sales of this product are about 300-...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D233/64A61P27/12A61Q19/08
Inventor 陆建刚邢健
Owner SUZHOU FUSHILAI PHARMA CO LTD
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