Advantame
[CAS# 714229-20-6]

Identification

• Classification: Food additive >> Sweetener
• Name: Advantame
• Synonyms: (3S)-3-[3-(3-hydroxy-4-methoxyphenyl)propylamino]-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid;hydrate
• Protein Sequence: DF
• Molecular Formula: C₂₄H₃₂N₂O₈
• Molecular Weight: 476.52
• CAS Registry Number: 714229-20-6
• SMILES: COC1=C(C=C(C=C1)CCCN[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)OC)O.O

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovory and Applicatios

Advantame is an artificial sweetener derived from aspartame and vanillin, recognized for its intense sweetness and high stability. Structurally, it is an N-[N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, combining the peptide backbone of aspartame with a vanillyl substituent. This design enhances its sweetness potency and resistance to hydrolysis, allowing it to retain flavor under heat, acidic conditions, and during storage. Advantame is reported to be approximately 20,000 times sweeter than sucrose by weight, making it effective at very low concentrations.

The synthesis of advantame involves a multi-step peptide coupling process starting from L-phenylalanine and aspartic acid derivatives. The vanillylpropyl group is introduced through an amide linkage to the aspartyl moiety, followed by methyl esterification to form the final structure. Careful protection and deprotection strategies are employed to ensure selective reaction at the desired functional groups, minimizing racemization and side reactions. The final product is purified by crystallization or chromatographic methods to achieve a high-purity sweetener suitable for food applications.

Advantame’s primary application is as a high-intensity sweetener in food and beverages, particularly in products requiring heat stability or acidic conditions, such as baked goods, soft drinks, and confectionery. Unlike aspartame, which can degrade under heat, advantame maintains sweetness during cooking or storage. Its low required usage level also reduces caloric contribution, supporting low-calorie and sugar-reduced formulations.

In addition to its sweetening properties, advantame has been evaluated for safety and metabolic stability. It is largely metabolized to amino acids and vanillin derivatives in the digestive tract, with minimal systemic exposure to the intact molecule. This metabolic profile contributes to its safety, making it suitable for general consumption, including in products targeted at individuals with dietary restrictions on sugar or caloric intake.

Advantame also finds use in combination with other sweeteners to create synergistic effects. When blended with compounds such as acesulfame potassium or sucralose, it can enhance overall sweetness perception while reducing potential aftertastes associated with individual sweeteners. This allows formulation flexibility and improved sensory profiles in processed foods.

Physically, advantame is typically obtained as a crystalline powder with low hygroscopicity, good solubility in water, and stability under normal storage conditions. It should be protected from extreme pH, strong oxidants, or prolonged high temperatures to preserve its chemical integrity. Proper handling ensures consistent sweetness and performance in various food matrices.

Overall, advantame is a chemically engineered high-intensity sweetener featuring a peptide-based backbone combined with a vanillylpropyl moiety. Its exceptional sweetness, heat and acid stability, and low caloric contribution make it a valuable ingredient in food and beverage applications, enabling sugar reduction while maintaining desirable taste and stability.

References

2019. Theoretical Risk Assessment of Dietary Exposure to Advantame among the Chinese Population. Biomedical and Environmental Sciences, 32(12).
DOI: 10.3967/bes2019.117

2015. [Determination of a new sweetener advantame in food by ultra-high performance liquid chromatography-tandem mass spectrometry]. Se Pu, 33(10).
DOI: 10.3724/sp.j.1123.2015.01028

2012. A two-generation reproductive toxicity study of the high-intensity sweetener advantame in CD rats. Food and Chemical Toxicology, 50.
DOI: 10.1016/j.fct.2011.07.002