CAS number：22839-47-0
molecular formula：C14H18N2O5
molecular weight：294.31
EINECS number：245-261-3

English synonyms

c-mer;Monoclonal Anti-MERTK antibody produced in mouse;RP38;E962;Asp-Phe-OMe H-Asp-Phe-OMe N-(L-α-Aspartyl)-L-phenylalanine methyl ester N-L-alpha-Aspartyl-L-phenylalanine 1-Methyl Ester L-Aspartyl-L-phenylalanine methyl ester;L-ASPARTYL-L-PHENYLALANINE METHYL ESTER;L-ASP-PHE METHYL ESTER;Asp-Phe-OMe

Related categories

Other biochemical reagents; carbohydrates; non-sugar sweeteners; food sweeteners; biochemical reagents; amino acids; raw materials; aspartame; food additives; sweeteners; flavoring agents (flavor enhancers); sweeteners Food Additives; Small Molecule Inhibitors; Amino Acids; Vitamins; Reference Substances; Sour Agents; Raw Materials; Biochemical Reagents - Amino Acids; Intermediates; Feed ADDITIVES;Biochemistry;Oligopeptides;Peptide Synthesis;Sweeteners;Food & Flavor Additives;Amines;Aromatics;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;NUTRASWEET;Food additive;Pyridines;Other raw materials;Drug impurities and intermediates;Pharmaceutical raw materials; Pharmaceutical, pesticide and dye intermediates; chemical materials; additives; organic chemical raw materials; additives; chemical raw materials; other raw materials and intermediates; chemical reagents; general biochemical reagents-amino acids; flavors and fragrances; biological reagents; catalog peptides

Introduction

Aspartame is an artificial sweetener that belongs to the amino acid dipeptide derivatives and was discovered by chemists in 1965 when developing ulcer drugs. It has low dosage, high sweetness (150-200 times the sweetness of sucrose), good taste, can improve the flavor of citrus and other fruits, reduce calories, does not cause dental caries, and is more toxic than saccharin and other synthetic sweeteners It has low advantages and is widely used in beverages, diabetic foods and some weight-loss health foods. The formula of cola we drink in our daily life once contained this product.

Chemical properties

 White crystalline powder, odorless, strong sweet taste, pure sweet taste, 100~200 times sweeter than sucrose. The melting point is 235°C (decomposition). It has the general properties of amino acids. It is stable under dry conditions or within the range of Ph value 2-5, can be hydrolyzed in strong acidic aqueous solution to produce monomeric amino acids, and can be cyclized into diketopiperazine under neutral or alkaline conditions. The solubility in water (25°C) is related to the Ph value, which is 10.2% when the Ph value is 7.0, and 18.2% when the Ph value is 3.72. The isoelectric point at 25°C is Ph value 5.2. Oral LD50 of mice > 10g/kg, Adl 0~40mg/kg (FAO/WHO, 1994)

Use

●  Aspartame is a synthetic low-calorie sweetener, often used in combination with sucrose or other sweeteners. It can be used in all kinds of food, and it can be used in appropriate amount according to the production needs. The general dosage is 0.5g/kg.

●  Used as a food additive, it is a high-sweetness nutritional sweetener

●  Non-nutritive sweeteners. Flavor enhancer.

●  According to my country's GB2760-90 regulations, it can be used in all kinds of food, and the maximum usage depends on the normal production needs. According to the regulations of FAO/WHO (1984), it can be used for sweet food, dosage 0.3%, gum 1.0%, beverage 0.1%, breakfast cereal 0.5%, and low sugar preparation for diabetes, hypertension, obesity, cardiovascular patients Class, low-calorie health food, the dosage depends on the need. Can also be used as a flavor enhancer.
Aspartame is a dipeptide synthesized from L-aspartic acid and L-phenylalanine (necessary nutrients for the human body), which can be completely absorbed and metabolized by the human body. It is non-toxic and harmless, safe and reliable, and has a pure taste Cool and refreshing, it resembles sucrose, but its sweetness is 200 times that of sucrose, and its calories are only 1/200 of that of sucrose. Regular consumption does not produce toothache, does not affect blood sugar, and does not cause obesity, high blood pressure, and coronary heart disease. It has been identified as A (1) sweetener by the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), and has been approved for use in more than 130 countries and regions in the world. It is widely added to various foods, non-staple foods and various soft and hard drinks, and more than 4,000 varieties of aspartame have been used. It can be used as a food additive and a nutritious sweetener with high sweetness. Packing: 25 kg fiber cardboard drum, lined with plastic bags.

Production method

●  From the condensation of L-aspartic acid and L-phenylalanine methyl ester.

●  Condensed from L-aspartic acid and L-phenylalanine methyl ester hydrochloride:

●  The preparation of aspartame usually has two kinds of chemical synthesis and enzymatic synthesis.

●  enzymatic synthesis
Tao Guoliang, Department of Chemistry, Wuhan University and others gave the following synthetic route:
Preparation of I Add 0.5mmol benzyloxycarbonyl aspartate, 1.5mmol phenylalanine methyl ester hydrochloride and 2.5mL water into a 25mL Erlenmeyer flask, adjust the pH value to 6 with ammonia water, add 7mg thermophilic For protease, stir the reaction at 40°C for 6h. It was filtered, washed with distilled water, and dried to obtain 0.29 g of white solid (I), with a yield of 95.6% and a melting point of 116-118°C. Elemental analysis results: C 62.96%, H 6.09%. N 6.65%.
(2) Preparation of II Add 0.5 g of sample I and 20 mL of 3 mol/L hydrochloric acid into a 25 mL Erlenmeyer flask, and stir and react at 45° C. for 0.5 h. Filtration, washing with distilled water, and drying gave 0.32 g of product II with a yield of 92% and a melting point of 129-131°C. Elemental analysis results: C 61.45%, H 5.42%, N 6.82%.
Preparation of III Add 0.2g of palladium-carbon (10%) catalyst, 20mL of glacial acetic acid, and 5mL of water into a 100mL three-necked flask, and activate it by hydrogenation for 1.5h. Add 20mL of glacial acetic acid dissolved in 0.6g II, and stir and hydrogenate at 30°C for 6h. After the reaction was completed, filter and wash the catalyst three times with glacial acetic acid; concentrate the filtrate and washings to dryness under reduced pressure, add 15 mL of benzene, and continue to concentrate under reduced pressure to dryness to obtain a white solid, which was dried to obtain 0.38 g of product III, with a yield of 92.3% , melting point 245°C. Elemental analysis results: C 55.63%, H 6.23%, N 8.96%.
chemical synthesis
Using aspartic acid and phenylalanine as raw materials, it is synthesized through the steps of amino protection, internal anhydride, condensation, hydrolysis, and neutralization. Different protecting groups and methyl esterification sequences can have various synthetic methods. Such as adopting formyl as the process route of protecting group and methyl esterification after, its
Put 27mL of 95% methanol and 0.2g of magnesium oxide into a 250mL flask. After the magnesium oxide is dissolved, add 100mL of 98% acetic anhydride. At this time, the temperature gradually rises to 40°C. Add 67g of L-aspartic acid, raise the temperature to 50°C, stir and keep it warm for 2.5h, add 15mL of 98% acetic anhydride, continue to keep warm for 2.5h, add 16mL of isopropanol, continue to react for 1.5h, cool to room temperature after the reaction .
Add the above-mentioned internal anhydride into a 1000mL flask, then add 207mL ethyl acetate and 66Gl-phenylalanine, stir at 25~30°C for 1.5h, then add 126mL of glacial acetic acid, continue the reaction for 4.5h, remove the vacuum after the reaction Solvent, until the temperature of the reaction system is 65°C.
Then 45mL of 35% hydrochloric acid was added, the temperature was raised to 60°C, and the reaction was refluxed for 2h. After hydrolysis, carry out atmospheric distillation until the distillation temperature reaches 63°C (reaction system temperature 73°C), add 180mL of methanol, and continue atmospheric distillation until the system temperature is 85°C. After cooling to 25°C, the light ends were removed in vacuo.
Add 54mL of 35% hydrochloric acid, 9mL of methanol and 43mL of water to the above hydrolysis reaction solution, and perform esterification reaction at 20~30°C for 7 days. Then suction filter and wash with water to separate α-APM hydrochloride. Dissolve it in 600mL of distilled water, and neutralize it to Ph=4.5 with 5%-10% NaOH solution at 40°C. Cool to below 5°C, suction filter and wash to obtain the crude α-APM, and then dissolve it in a mixture of 500 mL methanol and water (volume ratio 1:2). After cooling and crystallization, suction filtration and washing, and vacuum drying, the yield is 45% (based on L-phenylalanine).
Japanese scholars propose an unprotected route:
Dissolve 90g of phenylalanine methyl ester hydrochloride in 450mL of water, neutralize with 24g of sodium carbonate, and then extract with two 350mL dichlorethylene to obtain phenylalanine methyl ester. Add 9g of acetic acid and 8mL of methanol to the extract, then add 15.2g of aspartic anhydride hydrochloride at -20°C, keep stirring for 30min, then add 350mL of hot water at 70~80°C and sodium carbonate (5.7g) solution 300mL. After extracting the remaining phenylalanine methyl ester twice with 150 mL of dichloroethylene, the pH value of the aqueous layer was adjusted to 4.8 with dilute hydrochloric acid. This aqueous solution was measured by paper electrophoresis to contain 18.2g (60% molar yield) of α-APM and 6.1g (20% molar yield) of β-APM. This aqueous solution was concentrated in vacuo to 100mL, and added. 30mL of 36% hydrochloric acid, put in the refrigerator overnight. 21.3 g of α-APM·HCl crystals were precipitated (yield 58%), and the crystals were filtered off and dissolved in 200 mL of water. The solution was stirred at 50°C, and the pH value was adjusted to 4.8 with 5% sodium carbonate solution, then placed in the refrigerator overnight, precipitated and filtered to obtain 13.0 g of α-APM crystals (yield 43%). The crystals were dissolved in 500 mL of water, passed through a Dowex 1×4 (acetate form) column (1×20 cm) at 45° C., and washed with 20 mL of water. The effluent was concentrated in vacuo with the washing liquid, and 11.2 g of α-APM crystals were precipitated. Yield 37%, melting point 235~236°C (decomposition), specific rotation αD22+32.0° (C=1, in acetic acid). Elemental analysis results: C 55.30%, H 6.19%, N 9.36%.

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