(3S)-3-azaniumyl-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoate

Base Information

• Chemical Name: (3S)-3-azaniumyl-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoate
• CAS No.: 22839-47-0
• Molecular Formula: C14H18N2O5
• Molecular Weight: 294.307
• Hs Code.: 29242990
• Mol file: 22839-47-0.mol

Synonyms:

Chemical Property of (3S)-3-azaniumyl-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoate

Chemical Property:

• Appearance/Colour: White powder or tablets
• Vapor Pressure: 2.6E-12mmHg at 25°C
• Melting Point: 242-248 °C
• Refractive Index: 14.5 ° (C=4, 15mol/L Formic Acid)
• Boiling Point: 535.8 °C at 760 mmHg
• PKA: pKa 3.19±0.01 (H2O t=25.0 I=0.100(NaCl))(Approximate);7.87±0.02(H2O t=25.0 I=0.100(NaCl))(Approximate)
• Flash Point: 277.8 °C
• PSA: 118.72000
• Density: 1.28 g/cm³
• LogP: 0.78010
• Storage Temp.: 2-8°C
• Solubility.: Sparingly soluble or slightly soluble in water and in ethanol (96 per cent), practically insoluble in hexane and in methylene chloride.
• Water Solubility.: Soluble in formic acid, dimethyl sulfoxide. Sparingly soluble in water and ethanol.
• XLogP3: -2.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 294.12157168
• Heavy Atom Count: 21
• Complexity: 374

Purity/Quality:

99.5% ^*data from raw suppliers

Aspartame ^*data from reagent suppliers

Safty Information:

• Safety Statements: 22-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: COC(=O)C(CC1=CC=CC=C1)NC(=O)C(CC(=O)[O-])[NH3+]
• Isomeric SMILES: COC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)[O-])[NH3+]
• Composition and Usage: Aspartame is the methyl-ester of the aspartate-phenylalanine dipeptide and is widely used as a sweetener in both the food and pharmaceutical industries. It is found in over 5000 food products globally, including low-calorie beverages, dessert mixes, yogurt, multivitamins, morning cereals, and medicines.
• Discovery and Approval: Invented in 1965 by James M. Schlatter during research on antiulcer drugs, aspartame's sweetness was discovered accidentally. Approved by the U.S. FDA in 1981, it is about 200 times sweeter than sugar with almost zero calories.
• Acceptable Daily Intake and Labeling: The acceptable daily intake of aspartame is 40 mg/kg body weight in Europe and 50 mg/kg body weight in the United States. Products containing aspartame must be labeled to inform consumers, especially those with phenylketonuria, as it contains phenylalanine.
• Metabolism and Risks: Aspartame is hydrolyzed and absorbed in the gastrointestinal tract, releasing methanol, aspartic acid, and phenylalanine. Prolonged consumption may pose risks, especially to phenylketonuria patients.
• Applications Beyond Sweetening: Aspartame has been used in encapsulation processes to improve properties like stability, taste, color, and texture, extending storage times. It finds applications in food, cosmetics, agrochemicals, and pharmaceuticals.
• Stability and Degradation: Aspartame is stable in solid form but degrades in solution, especially in high temperatures or pH values above 6. It also loses sweetness when reacting with certain flavorings, aldehydes, or ketones.
• Usage in Baking and Confectionery: Although decomposed by baking, aspartame salts, and metal complexes can protect it, allowing its use in pastries. Its high sweetness makes it common in confectionery products like chewing gums.
• Safety Assessment and Genotoxic Properties: Despite safety assessments by various regulatory bodies, few studies have tested aspartame's genotoxic properties in vivo and in vitro, and none were conducted according to GLP standards.
• General Description: Aspartame is a dipeptide sweetener synthesized using immobilized penicillinacylase, which selectively cleaves the N-phenacetyl protecting group from N-phenacetyl aspartame to yield aspartame and phenylacetic acid. This enzymatic method offers a more efficient and selective alternative to traditional synthesis routes by enabling the removal of the nitrogen protecting group under mild conditions (pH 7.5), with the reaction rate influenced by the substituents at the α-carboxyl group of aspartic acid and its absolute configuration.

Technology Process of (3S)-3-azaniumyl-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoate

There total 45 articles about (3S)-3-azaniumyl-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 90.0%

(S)-N-((S)-1-Methoxycarbonyl-2-phenyl-ethyl)-3-(2-p-tolyl-acetylamino)-succinamic acid (140233-83-6) → 4-tolylacetic acid (622-47-9) + L-Asp-L-Phe-OMe (22839-47-0,7421-84-3)

Guidance literature:

With penicillin amidase; at 25 ℃; for 3.8h; Rate constant; Product distribution;

DOI:10.1016/S0040-4020(01)88207-7

Reference yield: 87.0%

N-phenacetyl-α-L-aspartyl-L-phenylalanine methyl ester (101623-22-7) → phenylacetic acid (103-82-2) + L-Asp-L-Phe-OMe (22839-47-0,7421-84-3)

Guidance literature:

With pH 7.5; penicillinacylase on Eupergit C beads; In water; at 28 ℃;

DOI:10.1016/S0040-4039(00)84751-6

Reference yield: 84.0%

α-L-aspartyl-L-phenylalanine methyl ester hydrochloride (5910-52-1) → L-Asp-L-Phe-OMe (22839-47-0,7421-84-3)

Guidance literature:

With sodium carbonate; In water; at 20 ℃; for 0.5h; pH=5;

DOI:10.1002/anie.200903510

upstream raw materials:

Boc-Asp(OtBu)-Phe-OMe

Z-Asp(OBzl)-Phe-OMe

methyl (2S)-2-amino-3-phenylpropanoate

<(4S)-2,2-bis(trifluoromethyl)-5-oxo-1,3-oxazolidine-4-yl>acetate

Downstream raw materials:

N,N-dimethyl-L-aspartyl-L-phenylalanine methyl ester

methanol

L-Aspartic acid

L-phenylalanine

Refernces

IMMOBILIZED PENICILLINACYLASE: APPLICATION TO THE SYNTHESIS OF THE DIPEPTIDE ASPARTAME

10.1016/S0040-4039(00)84751-6

This research explores the application of immobilized penicillinacylase in the synthesis of the dipeptide sweetener aspartame. The purpose is to find a more selective and efficient method to replace the formyl group in the traditional synthesis route with a nitrogen protecting group that can be removed enzymatically. The researchers used penicillinacylase immobilized on Eupergit C beads to catalyze the conversion of N-phenacetyl aspartame into aspartame and phenylacetic acid at pH 7.5. The results showed that the enzyme selectively cleaved the phenacetyl group, and the rate of hydrolysis depended on the substituents at the α-carboxyl group of aspartic acid and the absolute configuration of aspartic acid.