Chemical-enzyme method for preparing D-basic amino acid hydrochloride

A technology of amino acid hydrochloride and amino acid, which is applied in the chemical-enzymatic field of preparing D-basic amino acid hydrochloride, can solve the problems of low resolution yield, low optical purity of D-lysine, and resolution conditions Difficult to control and other issues to achieve high optical activity and reduce process costs

Inactive Publication Date: 2012-03-28
CHONGQING UNIV OF POSTS & TELECOMM
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The main disadvantage of this method is that the resolution conditions are difficult to control, the resolution yield is low, and the optical purity of D-lysine is not high

Method used

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  • Chemical-enzyme method for preparing D-basic amino acid hydrochloride
  • Chemical-enzyme method for preparing D-basic amino acid hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1 : Preparation of DL-2, 5-N-diphenylacetylornithine

[0024] Add 52.9g (0.4mol) DL-ornithine and 40g NaOH (1.0mol) into 1000ml water, stir to dissolve. 128ml (0.97mol) of phenylacetyl chloride was added dropwise under ice bath conditions. After the dropwise addition was completed, the reaction was carried out overnight. Cool in an ice bath to 5°C, filter with suction, wash the solid with a small amount of deionized water, and dry to obtain 135.6 g of DL-2, 5-N-diphenylacetylornithine with a yield of 92%.

Embodiment 2

[0025] Example 2: DL-2, 5-N-diphenylacetylornithinase-catalyzed hydrolysis

[0026] Add 110.5g (0.3mol) of DL-2, 5-N-diphenylacetylornithine into 1000ml of water, and adjust the pH to 8.0 with ammonia water. 44 g of immobilized penicillin acylase was added, and the reaction was stirred at 30° C. for 24 h. Suction filtration to remove immobilized penicillin acylase. The filtrate was adjusted to pH 1-2 with concentrated hydrochloric acid, filtered with suction, the solid was washed with cold water, and dried to obtain 31.5 g of D-α-N-phenylacetylornithine with a yield of 42%.

Embodiment 3

[0027] Example 3: Preparation of D-ornithine hydrochloride

[0028] Dissolve 31.5g D-α-N-phenylacetylornithine in 200mL 6 mol / L concentrated hydrochloric acid, hydrolyze at 90°C for 12h, extract three times with ethyl acetate (200ml×3), evaporate the water layer to dryness under reduced pressure, add Dissolve the solid in 100ml of absolute ethanol, then add 100ml of propylene oxide, filter with suction, wash the solid with a small amount of ethanol, and dry to obtain 19.1g of D-ornithine hydrochloride, with a yield of 90%. The ee measured by HPLC is 99.6%.

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Abstract

The invention provides a chemical-enzyme method for preparing D-basic amino acid hydrochloride. The method comprises the following steps of: derivatizing DL-basic amino acid serving as a raw material to obtain DL-N-diphenyl acetyl basic amino acid by utilizing an acylating agent, hydrolyzing the DL-N-diphenyl acetyl basic amino acid by using immobilized penicillin acylase as a biocatalyst through non-stereo selectivity and enantioselectivity to obtain L-basic amino acid, phenylacetic acid and D-alpha-N-phenylacetyl basic amino acid; and performing acidolysis on the D-alpha-N-phenylacetyl basic amino acid to obtain phenylacetic acid and D-basic amino acid dihydrochloride, and performing treatment of epoxypropane to obtain the D-basic amino acid hydrochloride. The D-lysine hydrochloride and D-ornithine hydrochloride which are prepared by the method have the yield of more than 40 percent, and ee is more than 99 percent. The method has the characteristics of high yield and optical purity, simple process and the like, and is suitable for the large-scale production of the D-basic amino acid hydrochloride.

Description

technical field [0001] The invention relates to a chemical-enzymatic method for preparing D-basic amino acid hydrochloride, which belongs to the technical field of biocatalytic preparation of chiral drug intermediates. Background technique [0002] D-basic amino acids represented by D-ornithine and D-lysine are non-protein source chiral amino acids, which are usually prepared in the form of monohydrochloride and are widely used in the synthesis of chiral drugs. For example, a derivative of D-ornithine - D-α-difluoromethylornithine (D-DFMO, ifornithine) is an irreversible inhibitor of ornithine decarboxylase, which has been approved in the United States It is used in a topical cream for the removal of unwanted hair and possibly for tumor treatment. Tetrapeptide Tyr-D-Orn-Gly-PheNH formed by replacing the second amino acid of enkephalin with D-ornithine 2 , its physiological effect is tens of times stronger than that of enkephalin. Some amino acid antibiotics are mixed with...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P13/08C12P13/10C07C229/26C07C227/18
Inventor 夏仕文方国兰
Owner CHONGQING UNIV OF POSTS & TELECOMM
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