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Preparation method of alpha arylglycine

A radical and aromatic technology, applied in the field of new synthetic process routes of α-aryl amino acids, can solve the problems of long reaction time of phase transfer catalyst, low conversion rate, long synthesis steps, etc., and achieve good optical purity and chemical yield. High efficiency, high ligand recovery, and simple post-reaction treatment

Inactive Publication Date: 2016-08-24
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
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  • Application Information

AI Technical Summary

Problems solved by technology

In the above method for synthesizing optically pure α unnatural amino acids, there are generally the following problems: 1) the synthesis steps of the cyclic chiral template molecule are relatively long, and some uncommon reagents need to be used, which increases the synthetic effort. Cost, on the other hand, also makes the possibility of large-scale production very small; 2) The enolization reaction of bicyclic chiral template molecules usually uses strong bases such as n-butyllithium, diisopropyl 3) The enantioselectivity of the asymmetric strecker reaction is poor, and highly toxic cyanide is used; 4) The reaction time of the phase transfer catalyst is longer and the conversion rate is lower Wait

Method used

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  • Preparation method of alpha arylglycine
  • Preparation method of alpha arylglycine
  • Preparation method of alpha arylglycine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Synthesis of Phenyl-Substituted Ni Ligands

[0028] Dissolve 50mg Ni(II) chelate, 11μL iodobenzene, 63.68mg potassium phosphate, 11.55mg tetrakistriphenylphosphine palladium and 3.9mg tetrakistriphenylphosphine in 2ml of dioxane, reflux under nitrogen protection for 20 After 1 hour, the reaction solution was filtered, concentrated, and purified by silica gel column to obtain 42.4 mg of the target product with a yield of 74%. 1 H NMR (300MHz, CDCl 3 ): δ8.21-8.10(m, 3H), 7.81-7.72(m, 2H), 7.61-7.35(m, 5H), 7.28-7.23(m, 5H), 7.21-7.19(m, 1H), 7.03 -6.98(m, 1H), 6.69-6.68(m, 2H), 6.13-6.10(m, 1H), 4.84(s, 1H), 4.55-4.51(d, 1H), 3.67-3.59(d, 2H) , 3.57-3.47(m, 3H), 2.87-2.82(m, 2H), 2.59-2.55(m, 1H), 2.09-2.02(m, 2H); ESI-MS m / z=596.1[M+Na] +

Embodiment 2

[0030] Synthesis of 3-Chlorophenyl Substituted Ni Ligands

[0031] Dissolve 50 mg of Ni(II) chelate, 11 μL of 3-chlorobromobenzene, 63.68 mg of potassium phosphate, 11.55 mg of palladium tetrakistriphenylphosphine and 3.9 mg of tetrakistriphenylphosphine in 2 ml of dioxane, under nitrogen protection Under reflux for 20 hours, the reaction solution was filtered, concentrated, and purified by silica gel column to obtain 39.8 mg of the target product with a yield of 65%. 1 H NMR (300MHz, CDCl 3 ): δ8.18-8.08(m, 3H), 8.10(s, 1H), 7.70-7.63(m, 2H), 7.57-7.38(m, 5H), 7.43-7.38(m, 3H), 7.24-7.16 (m, 3H), 7.07-7.02 (m, 1H), 6.68-6.67 (m, 2H), 6.16-6.13 (m, 1H), 4.84 (s, 1H), 4.55-4.51 (d, 1H), 3.67 -3.59(d, 2H), 3.57-3.47(m, 3H), 2.87-2.82(m, 2H), 2.59-2.55(m, 1H), 2.09-2.02(m, 2H); ESI-MS m / z =608.1[M+1] +

Embodiment 3

[0033] Synthesis of 4-methylphenyl substituted Ni ligands

[0034] Dissolve 50 mg of Ni(II) chelate, 11 μL of 4-methylbromobenzene, 63.68 mg of potassium phosphate, 11.55 mg of tetrakistriphenylphosphine palladium and 3.9 mg of tetrakistriphenylphosphine in 2 ml of dioxane, under nitrogen protection Under reflux for 20 hours, the reaction solution was filtered, concentrated and purified by silica gel column to obtain 32.4 mg of the target product with a yield of 56%. 1 H NMR (300MHz, CDCl 3 ): δ8.19-8.08(m, 3H), 7.79-7.77(s, 1H), 7.68-7.66(s, 1H), 7.50-7.45(m, 2H), 7.42-7.35(m, 3H), 7.30 -7.27(m, 2H), 7.23-7.18(m, 2H), 7.11-6.99(m, 2H), 6.67(s, 2H), 6.15-6.09(m, 1H), 4.84(s, 1H), 4.55 -4.51(d, 1H), 3.67-3.59(d, 2H), 3.57-3.47(m, 3H), 2.87-2.82(m, 2H), 2.59-2.55(m, 1H), 2.32(s.3H) , 2.09-2.02 (m, 2H); ESI-MS m / z=610.2[M+Na] +

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Abstract

The invention relates to the field of pharmacy and concretely relates to a novel synthesis route of alpha arylglycine. The preparation method comprises contracting an arylated metal complex through a transition metal-catalyzed coupling reaction of a halogenated aryl compound and a metal complex and carrying out arylated metal complex dissociation to realize alpha arylglycine preparation. The preparation method is simple and economic and is suitable for synthesis of alpha arylglycine with a novel structure type.

Description

technical field [0001] The invention relates to the field of pharmacy, in particular to a new synthetic process route of alpha aryl amino acid. The method is simple and economical, and is suitable for synthesizing alpha aryl amino acid with novel structure type. Background technique [0002] Unnatural amino acids are used in genetically engineered drugs based on recombinant proteins, such as recombinant cytokines, protein hormones, recombinant plasma proteins, recombinant thrombolytic drugs, soluble receptors, therapeutic antibodies, recombinant medicinal animal and plant proteins, etc. It has important applications in biological drugs and vaccines such as therapeutic vaccines, nucleic acid drugs, and small molecule polypeptide drugs. On the other hand, unnatural amino acids are also important drugs themselves. They are important structural units of many commercial and research drugs, and are widely used in antibacterial, antiviral, anti-inflammatory, anticonvulsant, cytosta...

Claims

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Application Information

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IPC IPC(8): C07C227/18C07C227/30C07C229/36C07C253/30C07C255/42
Inventor 孙宏斌张帆孙恒之
Owner CHINA PHARM UNIV
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