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Non-natural chiral amino acid and biological catalysis desymmetrisation preparation method thereof

A chiral and compound technology, applied in the field of non-natural chiral amino acid and its biocatalytic desymmetry preparation, can solve the problems of poor selectivity and harsh chemical transformation requirements

Inactive Publication Date: 2012-12-05
INST OF CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Amides are an important class of organic synthesis intermediates. The chemical transformation of amides requires harsh conditions and poor selectivity, while the biotransformation of amides has the advantages of mild conditions and high selectivity. At present, it has been possible to start from nitriles in industry. Preparation of corresponding carboxylic acids and amide derivatives, and preparation of carboxylic acids from amides, especially the preparation of chiral amide carboxylate compounds with quaternary carbon centers and their amino acid derivatives by biotransformation desymmetry related reports

Method used

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  • Non-natural chiral amino acid and biological catalysis desymmetrisation preparation method thereof
  • Non-natural chiral amino acid and biological catalysis desymmetrisation preparation method thereof
  • Non-natural chiral amino acid and biological catalysis desymmetrisation preparation method thereof

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preparation example Construction

[0063] References for the preparation of malononitrile compounds with two different substituents: Enrique Diez-Barra; Antonio de la Hoz; Andres Moreno and Prado Sanchez-Verdu.J.CHEM.SOC.PERKIN TRANS.1991, 1, 2589. The preparation method of the compound not in the literature is the same as the preparation method of allylmethylmalononitrile.

[0064] The preparation method of allylmethylmalononitrile: dissolve NaH (5mmol) in the mixed solvent DMF (2mL) and THF (20mL), add the substrate malononitrile (10mmol), stir at 0°C for 1 hour, then add Allyl bromide (5mmol), continue stirring for 4 hours and add H 2 O (20mL), extracted three times with ethyl acetate (25), MgSO 4 Drying, removal of solvent, separation by column chromatography to obtain allyl malononitrile. Dissolve allyl malononitrile (2mmol) in acetone (10mL), add K 2 CO 3 (4mmol) and CH 3 I (10 mmol), stirred at room temperature for 3 hours, filtered, removed the solvent, and separated by column chromatography to obt...

Embodiment 1

[0067] Embodiment 1: preparation compound 1

[0068]

[0069] Specific implementation method:

[0070] 1) Take 2 grams of wet weight of Rhodococcus erythropolis AJ270 cells (Institute of Chemistry, Chinese Academy of Sciences), thaw at 30°C for 30 minutes, and use a buffer solution of dipotassium hydrogen phosphate and potassium dihydrogen phosphate (0.1M, pH 7.0, 50ml ) wash the thalline into the Erlenmeyer flat-bottomed flask with threaded mouth, disperse and shake well and put it into a shaker for activation at 30°C for 30 minutes, then add 1 mmol (156 mg) of the formula IV-1 at one time The compound was placed in a shaker at 30° C. and 200 rpm to carry out catalytic hydrolysis reaction. Whole reaction TLC monitors, stops reaction after reacting 0.5 hour, and gained reaction solution removes thalline by suction filtration of one layer of diatomaceous earth, washes filter residue three times with 20 milliliters of water successively, obtains the compound shown in formula...

Embodiment 2

[0074] Embodiment 2: preparation compound 2

[0075]

[0076] 1) Take two grams of wet weight of Rhodococcus erythropolis AJ270 cells (Institute of Chemistry, Chinese Academy of Sciences), thaw at 30°C for 30 minutes, and use a buffer solution of dipotassium hydrogen phosphate and potassium dihydrogen phosphate (0.1M, pH 7.0, 50ml ) wash the thalline into 150 milliliters of Erlenmeyer flat-bottomed flasks with threaded openings, disperse and shake well, and then put into a shaker to activate at 30°C for 30 minutes, then add 1 mmol (206 mg) of formula IV-2 at one time The compounds shown were placed in a shaker at 30° C. and 200 rpm for catalytic hydrolysis. Whole reaction TLC monitors, stops reaction after reacting 8h, and gained reaction solution is removed thalline through one layer of diatomaceous earth suction filtration, washes filter residue three times with 20 milliliters of water successively, obtains the compound shown in formula I-1 provided by the invention (R 1...

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Abstract

The invention discloses non-natural chiral amino acid compounds and a preparation method thereof. The non-natural chiral amino acid compounds are shown as a formula III. Raw materials for preparing the non-natural chiral amino acid compounds provided by the invention are obtained by using a Rhodococcus erythropolis AJ270 microbial system to catalytically hydrolyze prochiral malonamide compounds with different substituents. The dosage of Rhodococcus erythropolis AJ270 thalluses can be adjusted according to the dosage of substrate. Reaction solvent is commonly used buffer solution with a pH (potential of hydrogen) value being 6.0-8.0, the temperature is 20-37DEG C and reaction time is 0.1-120 hours. The Rhodococcus erythropolis AJ270 microbial catalytic system has the characteristics of fermented cultivation and convenience in storage. The method for preparing chiral monoamine carboxylic acid and dicarboxylic acid through biological conversion has the advantages of simplicity and convenience in operation, high reaction efficiency, moderate reaction conditions, high enantioselectivity, easiness in product separation and high product purity, and can be used for synthesizing non-natural chiral amino acid.

Description

technical field [0001] The invention relates to a non-natural chiral amino acid and a biocatalytic desymmetry preparation method thereof. Background technique [0002] Amino acid compounds are the most widely existing compounds in living organisms, and are important components of living organisms, which play a very important role in the process of life. Because of its similar structure to natural amino acids, unnatural amino acids can often be used as substitutes for natural amino acids to study the role of different amino acids in life processes. Unnatural amino acids have shown certain promise as synthetic raw materials for some growth factor receptor proteins. drug activity. Currently commercialized unnatural amino acids include 2-Amino-2-methyl-3-phenylpropanoic acid (sold by Pure Chemistry Scientific Inc, USA) and 2-Amino-2-methyl-4-pentenoic acid (sold by hexagon labs, USA) . [0003] Biocatalysis is by far the most efficient, highly selective and environmentally fr...

Claims

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Application Information

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IPC IPC(8): C07C233/09C07C233/05C07C233/11C07C231/12C07C229/36C07C229/24C07C227/20C12P13/02A61P35/00A61P1/00C12R1/01
Inventor 王梅祥王德先张立彬
Owner INST OF CHEM CHINESE ACAD OF SCI
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