Alitame

Alitame [L-a-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamide] is a sweetener based on an amino acid. It is a very intense sweetener, possessing a sweetening power of about 2000 times that of sucrose. It also exhibits a clean sweet taste similar to sucrose. Although it 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 [9]. 

Alitame is the generic name for L-a-aspartyl-N-(2,2,4,4-tetramethyl-3-thetanyl)-D-alaninamide hydrate. Pfizer patented the sweetener in 1980 (Pfizer, 1980). It is a white, non-hygroscopic crystalline powder with good solubility in 

Alitame is an amino acid derivative and, therefore, not completely stable. It does hydrolyse in acid conditions, but is more stable than aspartame under certain conditions (Pfizer, 1987). Alitame is partially metabolised and absorbed in humans and is excreted as a mixture of its metabolites and unchanged alitame (Pfizer, 1987). 

The caloric value of alitame is 1.4 cal/g. JECFA have assigned an ADI of 0.1 rng/kg bw. The Committee on Toxicology (COT) ADI is 0.3 rng/kg bw. Alitame is currently permitted for food use in China and Australia. Submissions for approval have been made to the FDA. In Europe, a submission will be made to the EU Commission and also temporary approval will be sought in the United Kingdom via the Food Standards Agency (Koivistoinen, 2003). 

Amides of dipeptides consisting of L-aspartic acid and D-alanine are sweet (Table 8.11). The compound alitame is the N-3-(2,2,4,4-tetra-methyl)-thietanylamide of L-Asp-D-Ala (Formula 8.20) and with /sac,g(10) = 2000, it is a potential sweetener. 

Separation of the two dipeptide isomers (I, II) is possible since there are solubility differences between the two isomers as a consequence of their differing isoelectric points (IPi IPn). 

Other possible syntheses are based on a plas-tein reaction (cf. 1.4.6.3.2) with an N-derivatized aspartic acid and phenylalanine methylester or on bacterial synthesis of an Asp-Phe polymer, achieved by genetic engineering techniques, enzymatic cleavage of the polymer to Asp-Phe, followed by acid or enzyme catalyzed esterification of the dipeptide with methanol. 

Since the second amino acid has a D configuration, its side chain must be small, corresponding to the structure activity relationships discussed for dipeptide esters of the aspartame type (cf. 1.3.3). On the other hand, the carbonyl group should carry the largest possible hydrophobic residue. 

The stability of dipeptide amides of the alitame type is substantially higher than that of dipeptide esters of the aspartame type. Therefore, alitame can also be used in bread and confectionery. 

Adame-, L-aspartyl-D-alanine-N-(2,2,4,4-tetramethylthietan-3-yl)amide 3-(L-aspartyl-D-alaninamido)-2,2,4,4-tetramethyl-thietane. 

Alitame is an intense sweetening agent developed in the early 1980s and is approximately 2000 times sweeter than sucrose. It 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.  

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Alitame. A new group of aspartyl-dipeptide sweeteners became known to the pubHc in 1983 (95). Alitame [80863-62-3] L-aspartyl-D-alanine... 

Alitame (trade name Adame) is a water-soluble, crystalline powder of high sweetness potency (2000X, 10% sucrose solution sweetness equivalence). The sweet taste is clean, and the time—intensity profile is similar to that of aspartame. Because it is a stericaHy hindered amide rather than an ester, ahtame is expected to be more stable than aspartame. At pH 2 to 4, the half-life of aUtame in solution is reported to be twice that of aspartame. The main decomposition pathways (Fig. 6) include conversion to the unsweet P-aspartic isomer (17) and hydrolysis to aspartic acid and alanine amide (96). No cyclization to diketopiperazine or hydrolysis of the alanine amide bond has been reported. AUtame-sweetened beverages, particularly colas, that have a pH below 4.0 can develop an off-flavor which can be avoided or minimized by the addition of edetic acid (EDTA) [60-00-4] (97). 

Aliphatic solvents, alkyllithium compounds and, 14 250-251 Aliphatic sulfonates, 26 145 Aliquot samples, 13 413-415 analysis of, 13 416 Aliskren, 5 158 Alitame, 12 42 24 232 Alite, phase in Portland cement clinker, 5 471, 472t, 473t Alitretinoin, 25 790 Alizarin, color of, 7 331 Alizarin derivatives, 9 337 Alizarin pure Blue B, 4 361t Alkadienes, metathesis of, 26 923 Alkali/alkaline-earth cation recognition,... 

Sweeteners can be roughly divided into two groups bulk and intense sweeteners. Prodolliet (1996) and Gloria (2000) reviewed thoroughly the analysis and properties of intense sweeteners acesulfame-K, alitame, cyclamate, aspartame, glycyrrhizin, neohesperidin DC, saccharin, stevioside, sucralose and thaumatin. They are generally used in low calorie products such as diet... 

Alitame, L-a-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alanine amide, has undergone a series of safety studies. While most of the studies did not show adverse effects and no indications for carcinogenicity were found, a dose-dependent increase in liver weights was found at levels above 100 mg/kg which was identified as the no-effect level. While JECFA has allocated an ADI of 0-1 mg/kg12 only a few countries, but neither the European Union nor the USA, have approved alitame. 

Alitame is high potency sweetener, although it is more stable than aspartame, the control of sweetness of food is difficult while using it. 

What problem arises in using alitame as artificial sweetener ... 

In the future aspartame can expect to encounter competition from new high intensity sweeteners such as sucralose which is produced by Tate Lyle/Johnson Johnson and alitame (Pfizer), which have advantages such as even higher sweetness and, in the case of sucralose, heat stability. In response Nutrasweet are busy developing a new very high intensity sweetener (Sweetener 2000), which is reputed to be 10,000 times as sweet as sucrose. 

The type of solvent can affect the kinetics, and, as a consequence, the equilibrium is sometimes not reached within a reasonable time. For example, Kim and Shin studied the kinetically controlled synthesis of alitame precursor (Z-Asp(OEt)-D-Ala-NH2), and better results were obtained in the presence of dimethyl sulfoxide and 2-methoxyethyl acetate as adjuvants. These solvents promoted product precipitation while maintaining the reaction mixture in a homogeneous state, thus improving the conversion [64]. 

Saccharin imparts a sweetness that is pleasant at the onset but is followed by a lingering, bitter aftertaste. Sensitivity to this bitterness varies from person to person. At high concentration, however, most people can detect the rather unpleasant aftertaste. Saccharin is syneigistic with other sweeteners of different chemical classes. For example, saccharin—cyclamate, saccharin—aspartame, saccharin—sucralose, and saccharin—alitame combinations all exert synergy to various degrees. The blends, as a rule, exhibit less aftertaste than each of the component sweeteners by themselves. 

Alitame. A new group of aspartyl-dipeptide sweeteners became known to the public in 1983 (95). Alitame [80863-62-3 ], l- as p a rtyl- d - alanine A -(2,2,4,4-tetramethylthietan-3-yl)armde (16), was selected for commercial development. In 1986 Pfizer filed a food additive petition with the FDA. As of December, 1996, it was still pending. Alitame was approved for use as a sweetener by Australia in 1993, by China, Mexico, and New Zealand in 1994, by Indonesia in 1995, and by Colombia in 1996. 

Fig-1 Chemical structures of the intense sweeteners saccharin, sodium cyclamate, acesulfame-K, aspartame, alitame, dulcin, sucralose, and neohesperidin dihydrochalcone. 

Reverse-phase chromatography was used by Lawrence and Cbarbonneau (16) for the separation of cyclamate from saccharin, aspartame, acesulfame-K, alitame, sucralose, and dulcin. The system consisted of a Supelcosil LC-18 column and gradient elution of 0-100% mobile phase B [20 mM KH2P04 (pH 3.5) acetonitrile, 8 2 v/v] in mobile phase A [20 mM KH2P04 (pH 5.0) acetonitrile, 97 3 v/v]. 

Alitame [L- -aspartyl-/V-(2,2,4,4-tetramethyl-3-thioethanyl)-D-alaninamide] is an amino acid-based sweetener developed by Pfizer from L-aspartic acid, D-alanine, and an amine 2,2,4,4-tetraethylthioethanyl amine (Fig. 1). Its formula is CI4H2504N3S with a molecular weight of 331.06. It is produced under the brand name Aclame . It is a crystalline, odorless, nonhygro-scopic powder that is soluble in water (130 g/L at pH 5.6) and alcohol and significantly more stable than aspartame (Table 1). Alitame is 2000 times as sweet as sucrose and has a clean, sweet taste, with no unpleasant aftertaste. It blends with other sweeteners, such as acesulfame-K, saccharin, and cyclamate, to maximize the quality of sweetness (3,7-9). 

Sample preparation for HPLC analysis of alitame will depend on the type of food (16,33), and complex matrices may be clarified with Carrez solutions or by means of C18 disposable cartridge (33), as described in Sec. I.C. 

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