Aspartame chemical

This intense sweetener (8) is quoted as having the same effective sweetness as aspartame, but unlike aspartame it is sufficiently heat stable that it can be added at the beginning of the boil in high-boiled products. If a product with the same amount of acesulfame K is compared with one based on aspartame the taste will be different. In practice acesulfame K is not normally used on its own but is sometimes used with aspartame. Chemically, acesulfame K is the potassium salt of 6-methyl-l,2,3-oxathiazine-4(3//)-one-2,2 dioxide or 3,4-dihydro-6-methyl-l,2,3-oxathiazine-4-one 2,2-dioxide. It can be regarded as a derivative of acetoacetic acid. The empirical formula is C4H4N04KS and its molecular weight is 201.2. 

There are thousands of breweries worldwide. However, the number of companies using fermentation to produce therapeutic substances and/or fine chemicals number well over 150, and those that grow microorganisms for food and feed number nearly 100. Lists of representative fermentation products produced commercially and the corresponding companies are available (1). Numerous other companies practice fermentation in some small capacity because it is often the only route to synthesize biochemical intermediates, enzymes, and many fine chemicals used in minor quantities. The large volume of L-phenylalanine is mainly used in the manufacture of the artificial dipeptide sweetener known as aspartame [22389-47-0]. Prior to the early 1980s there was httle demand for L-phenyl alanine, most of which was obtained by extraction from human hair and other nonmicrobiological sources. 

An estimation of the amount of amino acid production and the production methods are shown ia Table 11. About 340,000 t/yr of L-glutamic acid, principally as its monosodium salt, are manufactured ia the world, about 85% ia the Asian area. The demand for DL-methionine and L-lysiae as feed supplements varies considerably depending on such factors as the soybean harvest ia the United States and the anchovy catch ia Pern. Because of the actions of D-amiao acid oxidase and i.-amino acid transamiaase ia the animal body (156), the D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is iaexpensively produced by chemical synthesis is primarily used as a feed supplement. In the United States the methionine hydroxy analogue is partially used ia place of methionine. The consumption of L-lysiae has iacreased ia recent years. The world consumption tripled from 35,000 t ia 1982 to 100,000 t ia 1987 (214). Current world consumption of L-tryptophan and i.-threonine are several tens to hundreds of tons. The demand for L-phenylalanine as the raw material for the synthesis of aspartame has been increasing markedly. 

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 synergistic with other sweeteners of different chemical classes. For example, saccharin—cyclamate, saccharin—aspartame, saccharin—sucralose, and saccharin—aUtame combinations all exert synergy to various degrees. The blends, as a rule, exhibit less aftertaste than each of the component sweeteners by themselves. 

Another advantage of biocatalysis is that chemo-, regio-, and stereoselectivities are attainable that are difficult or impossible to achieve by chemical means. A pertinent example is the production of the artificial sweetener, aspartame, which has become somewhat of an industrial commodity. The enzymatic process (Fig. 2.31), operated by the Holland Sweetener Company (a joint venture of DSM and Tosoh), is completely regio- and enantiospecific (Oyama, 1992). 

FIG. 25 Chemical structures of (a) erythritol, (b) sodium saccharin, and (c) aspartame. 

Bell et al. (2002) investigated the relationship between water mobility as measured by oxygen-17 NMR (transverse relaxation rate obtained from linewidth at half-height) and chemical stability in glassy and rubbery polyvinylpyrrolidone (PVP) systems. Reported results suggest that water mobility in PVP model systems was not related to Tg. The study did not find a link between water mobility and reaction kinetics data (half-lives) for degradation of aspartame, loss of thiamin and glycine, and stability of invertase. 

Bell, L.N. and Hageman, M J. 1994. Differentiating between the effects of water activity and glass transition dependent mobility on a solid state chemical reaction Aspartame degradation. J. Agric. 

Deep-ultraviolet chemically amplified resists, 15 163-181 Deepwater barges, 25 327 Deep-well turbine pumps, 21 68 Deesterification, of aspartame, 24 227 DEET, 2 549t Defaunation, 10 871 D,E,F color scale, 7 310 Defect Action Levels (DALs), 23 160 Defects, in silicon-based semiconductors, 22 232... 

CE has been applied extensively for the separation of chiral compounds in chemical and pharmaceutical analysis.First chiral separations were reported by Gozel et al. who separated the enantiomers of some dansylated amino acids by using diastereomeric complex formation with Cu " -aspartame. Later, Tran et al. demonstrated that such a separation was also possible by derivatization of amino acids with L-Marfey s reagent. Nishi et al. were able to separate some chiral pharmaceutical compounds by using bile salts as chiral selectors and as micellar surfactants. However, it was not until Fanali first showed the utilization of cyclodextrins as chiral selectors that a boom in the number of applications was noted. Cyclodextrins are added to the buffer electrolyte and a chiral recognition may... 

This is confusing. Why don t risk assessors simply decide what level of exposure is safe for each chemical, and risk managers simply put into effect mechanisms to ensure that industry reaches the safe level Why should different sources of risk be treated differently Why apply a no risk standard to certain substances (e.g., those intentionally introduced into food, such as aspartame) and an apparently more lenient risk-henefit standard to unwanted contaminants of food such as PCBs, methylmercury, and aflatoxins (which the FDA applies under another section of food law) Why allow technological limitations to influence any decision about health What is this risk-henefit balancing nonsense Aren t some of these statutes simply sophisticated mechanisms to allow polluters to expose people to risk ... 

Other Food Industries. Aspartame is a synthetic dipeptide ester, L-asp-L-phe-OMe which is about 200 times as sweet as sucrose. It has recently been released for sale in North America and Europe by G. D. Searle. It was originally synthesized chemically and reported by Mazur et al. 38). Subsequent improved methods of synthesis have been developed which involve the use of metalloproteases such as thermolysin in reverse . Metalloproteases are used because, unlike the more common proteases, they have no esterase activity. 

Aspartame is a high intensity dipeptide sweetener, ca. 200 times as sweet as sncrose. It was originally developed by G.D.Searle Co. prior to their acqnisition by Monsanto. Chemically synthesised aspartame has rapidly acqnired a major share of the world high intensity sweetener market, particnlarly in soft drinks. Until recently it has all been snpplied by a monopoly snpplier, the Nntrasweet Corp (a Monsanto-AJinomoto joint ventnre) protected by prodnct patents. Recently biocatalytic methods... 

The enzyme process is not significantly cheaper than the chemical method so that the aspartame made by both methods are very competitive. 

Traditional commercial requirements for L-phenylalanine have been small (less than 50 ton/a) and had been satisfied by the use of aminoacylase to resolve chemically synthesised DL-N-acetylphenylalanine. However with the advent of aspartame as a high intensity sweetener a very big derived demand for L-phenylalanine was generated. As a result a number of companies began to develop bioconversion and fermentation processes to produce L-phenylalanine. 

Use of biocatalysts in combination with other separate chemical steps. aspartame, (S)-2-chloropropanoic acid, L-PAC... 

There are highly developed methods for chemical peptide synthesis, both solid phase methods and solution methods. This makes it rather difficult for the enzymatic methods to compete. However, the aspartame example shows that for peptides which have a big market it can be worthwhile to develop an enzymatic process. 

Sweet Taste. The mechanism of sweetness perception has been extensively studied because of its commercial importance. Many substances that vary in chemical structure have been discovered which are similar to the taste of sucrose. Commercial sweeteners include sucralose, acesulfame-K, saccharin, aspartame, cyclamate (Canada) and the protein thaumatin 4), Each sweetener is unique in its perceived sensation because of the time to the onset of sweetness and to maximum sweetness, ability to mask other sensations, persistence, aftertaste and intensity relative to sucrose [TABLE IT. For example, the saccharides, sorbitol and... 

For the purpose of synthesizing flavor peptides or proteins in large scale, we developed "protein recombination method" and "enzymatic synthesis using chemically modified enzyme". "Protein recombination method" was applied to the synthesis of C-terminal portion of p-casein and its analog. Chymotrypsin was chemically modified by Z-DSP in aqueous solution. It was stable for organic solvents. Using this modified enzyme, we succeeded in the synfiiesis of Inverted-Aspartame-Type Sweetener "Ac-Phe-Lys-OH" in one step. 

Today, it is well-known that peptides or proteins exhibit various kinds of taste. Our group has been researching on the relationship between taste and structure of peptides, BPIa (Bitter peptide la, Arg-Gly-Pro-Pro-Phe-Ile-Val) (7 as a bitter peptide, Om-p-Ala-HCl (OBA), Om-Tau-HCl as salty peptides(2j, and "Inverted-Aspartame-Type Sweetener" (Ac-Phe-Lys-OH) as a sweet peptide(5). The relationship between taste and chemical structure was partly made clear. Since commercial demand for these flavor peptides is increasing, we need to develop new synthetic methods which can prepare these peptides in large scale. We developed the following two methods (1) protein recombination method as a chemical method, (2) enzymatic synthesis using chemically modified enzyme as a biochemical method. 

Aspartame is synthesized using the L enantiomer of phenylalanine. The L enantiomer is separated from the D enantiomer, the racemic mixture, by reacting it with acetic anhydride (CH3C0)20) and sodium hydroxide. The product of this reaction is then treated with the enzyme porcine kidney acylase. An organic extraction with acid yields the L enantiomer in the aqueous layer and the D enantiomer in the organic layer. The L-phenylalanine is reacted with methanol and hydrochloric acid to esterify the COOH group on phenylalanine. The esterified L-phenyalanine is then reacted with aspartic acid, while using other chemicals to prevent unwanted side reactions, to produce aspartame. 

Figure 12.3 Effect of basic inorganic salt on K2C03 per mole Phe-OMe HCl. Reprinted with initial rate of protease-catalyzed synthesis permission from Erbeldinger, M. Ni, X. of Z-aspartame (0.1 mmol Z-Asp, 0.1 mmol Hailing, P.). Biotechnol. Bioeng., 2001, 72, 69. Phe-OMe HCl) with varied amounts of KHC03 Copyright (2001) American Chemical Society, (triangles) and K2C03 (circles). The x-axis unit [51]. is equivalent to 1 mol of KHC03 or 0.5 mol...

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

Aspartame is an intense sweetener first discovered in 1965 by J. Schlatter it is available under the brand names of Nutrasweet , Equal , and Canderel . Chemically, aspartame is N-L-a-aspartyl-L-phenylalanine methyl ester (Fig. 1), withamolecularformulaofC14H 805N2 (MW = 294.30). It is a white, odorless, crystalline powder. It is slightly soluble in water and sparingly soluble in alcohol. The solubility increases as the pH is lowered (2,6,57). It has 100-200 times the sweetness of sucrose and exhibits a sweet, clean taste and a sweetness profile similar to that of sucrose, without bitter or metallic aftertaste (Table 1). However, it displays a slow onset of sweetness coupled with lingering sweet taste. It extends and intensifies tastes and enhances fruit flavors. Aspartame exhibits synergism, a superior taste profile, and improved stability when used with other sweeteners (1,4,14,55,75). 

Salt of aspartame and acesulfame. A salt of aspartame and acesul-fame is now available. The product is a chemical combination of aspartame and acesulfame in a ratio of 64 36 on a weight basis. This product was given 2 years temporary national approval in the United Kingdom (Statutory Instrument 2003 number 1182). It also has temporary approval in The Netherlands (Staatscourant, 17 July 2002), and it can be used in the United States, Canada, China, Mexico and Russia. In 2004, amendment of the EU Sweetener Regulation saw extension of the approval to all EU markets. In solution, the salt breaks up to form aspartame and acesulfame. The relative sweetness is 350 (HSC, 2003). 

James M. Schlatter, American chemist, combines two amino acids and obtains a sweet-tasting substance. This chemical is about 200 times sweeter than sugar and is named aspartame. In 1983, it is approved for use in carbonated beverages. It becomes the most widely used artificial sweetener. 

The synthesis of aspartame can be achieved by numerous chemical and enzymatic methods of amide bond formation between (Z)-aspartic acid and either (Z,)-phenylalanine or (Z)-phenylalanine methyl ester. Both approaches have been thoroughly reviewed [10]. The chief difficulty with chemical methods is formation of the non-sweet P-isomer as a by-product. 

Two chemical methods have been devised to avoid formation of the nonsweet (Z)-P-aspartyl compound. The first of these entails the use of an activated precursor in which the P-carboxyl group is protected [11]. In this method, the approach described in Scheme 1 is used. This route gives an overall aspartame yield of about 55%. The rate of formation of the product depends on the degree of hydrolysis of the intermediate aspartyl P-methyl ester to the diacid (not shown), before entering the esterification medium (steps 3 and 4). 

The enzymatic approach for the synthesis of aspartame has the advantage of producing only the (Z,)-a-aspartyl compound (the sweet diastereomer). The less expensive racemic (DZ)-phenylalanine can be used as the starting material. The unreacted (D)-phenylalanine can be recovered and racemized for further reaction. By contrast, the chemical methods used industrially also produce the (L)-p-aspartyl compound (non-sweet) in 10-40% yield, for which a purification step is needed. In 1999, the world market for enzymatically synthesized aspartame was reported to be 800 million US [13]. 

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