ALITAME

Alitame is a white nonhygroscopic crystalline powder,  odorless or having a slight characteristic odor.
Alitame is an amino acidbased sweetener developed by Pfizer Central Research from l-aspartic acid, d-alanine, and 2,2,4,4-tetraethylthioethanyl amine. 
Alitame a terminal amide group instead of the methyl ester constituent of ASP was used to improve the hydrolytic stability. 

CAS Number: 80863-62-3
Molecular Formula: C14H25N3O4S
Molecular Weight: 331.43
EINECS Number: 1312995-182-4

Synonyms: (3s)-3-amino-4-oxo-4-[[(2r)-1-oxo-1-[(2,2,4,4-tetramethylthietan-3-yl)amino]propan-2-yl]amino]butanoic acid, (S)-3-amino-4-(((R)-1-amino-1-oxopropan-2-yl)(2,2,4,4-tetramethylthietan-3-yl)amino)-4-oxobutanoic acid, (S)-3-Amino-4-oxo-4-(((R)-1-oxo-1-((2,2,4,4-tetramethylthietan-3-yl)amino)propan-2-yl)amino)bu, (S)-3-((R)-1-(2,2,4,4-TETRAMETHYLTHIETAN-3-YLCARBAMOYL)ETHYLCARBAMOYL)-3-AMINOPROPANOIC ACID, l-alpha-aspartyl-n-(2,2,4,4-tetramethyl-3-thietanyl)-d-alaninamide, l-α-aspartyl-N-(2，2，4，4-tetramethyl-3-thietanyl)-D-alaninamide, CP 54802, (S)-3-AMino-4-oxo-4-(((R)-1-oxo-1-((2,2,4,4-tetraMethylthietan-3-yl)aMino)propan-2-yl)aMino)butanoic acid

Alitame is stable for over a year at pH 6–8 and room temperature and withstands pasteurization. 
However, prolonged storage of acidic solutions at high temperatures or in combination with certain ingredients (hydrogen peroxide or sodium bisulfite) may produce off-flavors. 
In the presence of high levels of reducing sugars, alitame can undergo Maillard reactions.

The incorporation of d-alanine as a second amino acid in place of l-phenylalanine has resulted in optimum sweetness. 
The increased steric and lipophilic bulk on a small ring with a sulfur derivative has provided a very sweet product and good taste qualities.
Alitame offers several benefits such as stability at high temperatures and a broader pH range. 

Alitame is an artificial sweetener that belongs to the class of dipeptide sweeteners, which means it is chemically composed of two amino acids linked together, specifically L-aspartic acid and a derivative of alanine. 
Alitame was developed as a high-intensity sweetener that is many times sweeter than sucrose (table sugar), with estimates suggesting it is approximately 2000 times sweeter, allowing it to be used in very small amounts to achieve desired sweetness levels. 
Because of its intense sweetness and favorable taste profile that closely mimics natural sugar without a bitter aftertaste, alitame has been considered a valuable ingredient in the food and beverage industry, particularly for low-calorie or sugar-free products such as diet sodas, chewing gums, desserts, and tabletop sweeteners. 

In addition to its sweetness, alitame is relatively stable under heat and acidic conditions, making it suitable for various cooking and baking applications where other sweeteners might degrade or lose potency. 
Despite its advantages, alitame has not been approved for widespread use in all countries due to regulatory hurdles and safety evaluations that have taken place over the years, although it has received approval in some regions for specific uses. 
Research into alitame’s safety profile has generally found it to be non-toxic and safe for human consumption at approved levels, but ongoing monitoring and assessment continue as with all artificial sweeteners. 

Alitame represents an important development in sweetener technology, offering a potent and sugar-like alternative for reducing caloric intake without compromising taste.
Alitame is an aspartic acid-containing dipeptide sweetener. 
It was developed by Pfizer in the early 1980s and currently marketed in some countries under the brand name Aclame.

Most dipeptides are not sweet, but the unexpected discovery of aspartame in 1965 led to a search for similar compounds that shared its sweetness. 
Alitame is one such second-generation dipeptide sweetener. 
Neotame, developed by the owners of the NutraSweet brand, is another.

Alitame is about 2000 times sweeter than sucrose (table sugar), about 10 times sweeter than aspartame, and has no aftertaste. 
Its half-life under hot or acidic conditions is about twice as long as aspartame's, although some other artificial sweeteners, including saccharin and acesulfame potassium, are more stable yet. 
Unlike aspartame, alitame does not contain phenylalanine, and can therefore be used by people with phenylketonuria.

Alitame has approved for use in Mexico, Australia, New Zealand and China. 
Danisco has withdrawn its petition for using alitame as a sweetening agent or flavoring in food in US.
Alitame is a dipeptide-based amide derived from aspartate and alanine that is 2000 times sweeter than sucrose. 

Alitame is currently undergoing safety evaluation trials as a sweetener.
Alitame is prepared by a multistep synthesis involving the reaction between two intermediates, (S)-[2,5-dioxo-(4-thiazolidine)] acetic acid and (R)-2-aminoN-(2,2,4,4-tetramethyl-3-thietanyl)propanamide. 
The final product is isolated and purified through crystallization of an alitame / 4-methylbenzenesulfonic acid adduct followed by additional purification steps, and finally recrystallization from water as the 2.5 hydrate. 

Alitame is a high-intensity sweetener formed from the amino acids L-aspartic acid and D-alanine, and an amine derived from thietane.
Alitame is an artificial sweetener developed by Pfizer in the early 1980s and currently marketed in some countries under the brand name Aclame.

Like aspartame, alitame is an aspartic acid-containing dipeptide. Most dipeptides are not sweet, but the unexpected discovery of aspartame in 1965 led to a search for similar compounds that shared its sweetness. 
Alitame is one such second-generation dipeptide sweetener.

Melting point: 136–147°
alpha: D25 +40 to +50° (c = 1 in water)
Boiling point: 608.5±55.0 °C (Predicted)
Density: 1.25±0.1 g/cm³ (Predicted)
Solubility: Methanol (Slightly)
Form: Solid
pKa: 3.71±0.10 (Predicted)
Color: White to Off-White
Odor: odorless
Odor Type: odorless
LogP: 1.508 (est)

Alitame is a sweetener based on an amino acid. 
Alitame is a very intense sweetener, possessing a sweetening power of about 2000 times that of sucrose. 
Alitame also exhibits a clean sweet taste similar to sucrose. 

Alitame is metabolized, so little is needed that its caloric contribution is insignificant. 
Alitame is prepared from the amino acids, L-aspartic acid, D-alamine, and a novel amine.
Alitame may be synthesized by a number of routes.

Alitame is dissolved in water and L-aspartic acid N-thiocarboxyanhydride is then added in portions with vigorous stirring, maintaining the pH of 8.5–9.5. 
The pH is then adjusted to 5.5 and p-toluenesulfonic acid monohydrate is added over a period of one hour. 
The precipitated crystalline p-toluenesulfonate salt is collected by filtration. 

To obtain alitame from its salt, a mixture of Amberlite LA-1 (liquid anion exchange resin), dichloromethane, deionized water, and the salt is stirred for one hour, resulting in two clear layers. 
The aqueous layer is treated with carbon, clarified by filtration, and cooled to crystallize alitame.
Alternatively, Alitame is condensed with anNprotected form of D-alanine to give alanyl amide. 

This is then coupled to a protected analogue of L-aspartic acid to give a crude form of alitame. 
The crude product is then purified.
Alitame's unique structure as a dipeptide sweetener not only contributes to its remarkable sweetness potency but also affects how it interacts with taste receptors on the human tongue, resulting in a clean, sugar-like taste that lacks the lingering bitterness or metallic aftertaste common to some other artificial sweeteners such as saccharin or aspartame. 

Its metabolic pathway is another key aspect: alitame is partially broken down in the digestive system into amino acids that are then utilized or metabolized by the body, which contributes to its classification as a low-calorie sweetener and may provide some reassurance regarding its safety and nutritional impact. 
From a manufacturing standpoint, alitame can be produced through chemical synthesis, which allows for precise control over purity and consistency, though production costs have historically been higher compared to more common sweeteners, influencing its market penetration and availability. 

Due to its high sweetness intensity, only minuscule amounts of alitame are needed in formulations, which means that even slight variations in concentration can significantly affect the sweetness level of the final product, necessitating careful formulation and quality control. 
Additionally, alitame’s stability across a broad range of pH values and temperatures makes it suitable for inclusion in a wide variety of food products, including carbonated beverages, baked goods, and dairy products, without significant loss of sweetness or degradation. 
Despite these promising attributes, consumer acceptance and regulatory approval remain crucial factors that have limited its widespread adoption compared to other sweeteners like sucralose or stevia. 

Alitame is an intense sweetener, with a sweetness potency 2000 times greater than that of sucrose. 
Alitame is a dipeptide of L-aspartic acid and D-alanine, with a terminal N-substituted tetramethylthietanyl-amine moiety. 

Alitame is prepared by a multistep synthesis involving the reaction between two intermediates, (S)-[2,5-dioxo-(4-thiazolidine)] acetic acid and (R)-2-amino-N-(2,2,4,4-tetramethyl-3-thietanyl) propanamide. 
The final product is isolated and purified by crystallization of an alitame-4-methylbenzenesulfonic acid adduct, followed by additional purification steps, and finally recrystallization from water.

Uses Of Alitame:
Alitame is a sweetener based on an amino acid. 
Alitame is a very intense sweetener, possessing a sweetening power of about 2000 times that of sucrose. 
Alitame also exhibits a clean sweet taste similar to sucrose. 

Although Alitame is metabolized, so little is needed that its caloric contribution is insignificant. 
Alitame is prepared from the amino acids, L-aspartic acid, D-alamine, and a novel amine.
Alitame is a dipeptide amide derivative of aspartic acid used as an artificial sweetener. 

Alitame is about ten times sweeter than Aspartame (A790015) with a half life about twice as long.
Alitame’s remarkable sweetness potency means that food technologists can formulate products with minimal impact on the overall recipe’s bulk or moisture content, which is especially important in delicate formulations like low-fat or sugar-free baked goods where sugar also acts as a texturizer and humectant. 
Because alitame does not promote tooth decay, it is commonly included in oral care products such as sugar-free gums, mints, and toothpastes, where it provides a pleasant sweetness without contributing to dental caries. 

Additionally, alitame’s compatibility with other sweeteners enables it to be used in combination blends, allowing manufacturers to tailor sweetness profiles that balance taste, cost, and stability, often mitigating any off-flavors that individual sweeteners may impart when used alone. 
In the beverage industry, alitame is valuable for sweetening diet sodas, flavored waters, and energy drinks, where maintaining a consistent and appealing sweetness is essential despite storage and temperature fluctuations. 
The pharmaceutical sector benefits from alitame’s use as a taste-masking agent not only in oral medications but also in chewable vitamins and supplements, improving patient adherence, particularly among children and the elderly.

Alitame is an intense sweetening agent developed in the early 1980s and is approximately 2000 times sweeter than sucrose. 
Alitame has an insignificant energy contribution of 6 kJ (1.4 kcal) per gram of alitame.
Alitame is currently primarily used in a wide range of foods and beverages at a maximum level of 40–300 mg/kg.

Alitame is primarily used as a high-intensity artificial sweetener in various food and beverage products, especially those designed to provide a sweet taste while significantly reducing caloric content, making it an attractive option for people seeking to manage their weight or blood sugar levels. 
Its intense sweetness, which is roughly 2000 times that of sucrose, allows manufacturers to use only very small quantities to achieve the desired level of sweetness, thereby minimizing any impact on the product’s texture or bulk that larger amounts of sugar or other sweeteners might cause. 

Because alitame is stable under heat and across a wide range of pH levels, it is well-suited for use in baked goods, confectionery, dairy products, soft drinks, chewing gum, and tabletop sweeteners, where other sweeteners might break down or lose potency during processing or storage. 
Moreover, its clean and sugar-like taste profile, without bitter or metallic aftertaste, makes it especially valuable in products where a natural sweet flavor is essential for consumer acceptance, such as in diet sodas, sugar-free desserts, and low-calorie snacks. 
Alitame is also used in pharmaceutical formulations to mask the unpleasant bitter taste of certain medications, thereby improving patient compliance, particularly in chewable tablets or syrups. 

Additionally, because it is a dipeptide-based sweetener that breaks down into amino acids, alitame can be incorporated into specialized nutrition products, such as those for diabetics or individuals requiring controlled sugar intake. 
Despite these many uses, the extent of alitame’s application varies by country due to differing regulatory approvals, with some regions permitting it in a wider range of products than others.
Alitame serves as a versatile and potent sweetening agent that helps manufacturers meet consumer demand for flavorful, low-calorie, and sugar-reduced foods and beverages.

Furthermore, because alitame’s sweetness intensity is not diminished by acidic conditions, it is particularly useful in citrus-flavored products and acidic syrups where other sweeteners might degrade. 
Although its adoption has been limited in some markets due to regulatory restrictions, ongoing research into its safety and sensory properties may pave the way for broader acceptance and use in future food and pharmaceutical applications.

Storage Of Alitame:
Alitame is stable in dry, room temperature conditions but undergoes degradation at elevated temperatures or when in solution at low pH. 
Alitame can degrade in a one-stage process to aspartic acid and alanine amide (under harsh conditions) or in a slow two-stage process by first degrading to its β-aspartic isomer and then to aspartic acid and alanine amide. 
At pH 5–8, alitame solutions at 238℃ have a half-life of approximately 4 years. At pH 2 and 238℃ the half-life is 1 year.

Safety Profile Of Alitame:
The Joint Expert Committee on Food Additives (JECFA) concluded that alitame was not carcinogenic and did not show reproductive toxicity. 
In 1996, an ADI of 0–1 mg/kg of body weight was allocated. It is approved for use in Australia, New Zealand, Mexico, and China. 
A food additive petition was submitted to the FDA in 1986, and approval is awaited. 

In the petition, the estimated daily intake is 0.34 mg/kg of body weight, which represents the amount if alitame is the only sweetener in the diet. 
The level at which no observed adverse effects occur in animals is 100 mg/ kg. 
Potential uses include baked goods, baking mixes, hot and cold beverages, dry beverage mixes, tabletop sweeteners, chewing gum, candies, frozen desserts, and pharmaceuticals. 

Alitame has been approved for use in some countries such as Australia, Mexico, New Zealand, and China, but not in the United States or the EU.
Alitame is a relatively new intense sweetening agent used primarily in foods and confectionary. 
It is generally regarded as a relatively nontoxic and nonirritant material.

Chronic animal studies in mice, rats, and dogs carried out for a minimum of 18 months at concentrations >100 mg/kg per day exhibited no toxic or carcinogenic effects. 
In people, no evidence of untoward effects were observed following ingestion of 15 mg/kg per day for two weeks.

Following oral administration 7–22% of alitame is unabsorbed and excreted in the feces. 
The remaining amount is hydrolyzed to aspartic acid and alanine amide. 
The aspartic acid is metabolized normally and the alanine amide excreted in the urine as a sulfoxide isomer, as the sulfone, or conjugated with glucuronic acid.