Sweeteners aspartame

Fumaric acid and malic acid [6915-15-7] are produced from maleic anhydride. The primary use for fumaric acid is in the manufacture of paper siting products (see Papermaking additives). Fumaric acid is also used to acidify food as is malic acid. Malic acid is a particularly desirable acidulant in certain beverage selections, specifically those sweetened with the artificial sweetener aspartame [22839-47-0]. 

There are numerous further appHcations for which maleic anhydride serves as a raw material. These appHcations prove the versatiHty of this molecule. The popular artificial sweetener aspartame [22839-47-0] is a dipeptide with one amino acid (l-aspartic acid [56-84-8]) which is produced from maleic anhydride as the starting material. Processes have been reported for production of poly(aspartic acid) [26063-13-8] (184—186) with appHcations for this biodegradable polymer aimed at detergent builders, water treatment, and poly(acryHc acid) [9003-01-4] replacement (184,187,188) (see Detergency). 

Sucrose occupies a unique position in the sweetener market (Table 3). The total market share of sucrose as a sweetener is 85%, compared to other sweeteners such as high fmctose com symp (HFCS) at 7%, alditols at 4%, and synthetic sweeteners (aspartame, acesulfame-K, saccharin, and cyclamate) at 4%. The world consumption of sugar has kept pace with the production. The rapid rise in the synthetic sweetener market during 1975—1995 appears to have reached a maximum. 

One of the most interesting uses for cinnamic acid in recent years has been as a raw material in the preparation of L-phenylalanine [63-91-2] the key intermediate for the synthetic dipeptide sweetener aspartame (25). Genex has described a biosynthetic route to L-phenylalanine which involves treatment of immobilized ceUs of R rubra containing the enzyme phenylalanine ammonia lyase (PAT,) with ammonium cinnamate [25459-05-6] (26). 

Different optical enantiomers of amino acids also have different properties. L-asparagine, for example, tastes bitter while D-asparagine tastes sweet (see Figure 8.3). L-Phenylalanine is a constituent of the artificial sweetener aspartame (Figure 8.3). When one uses D-phenylalanine the same compound tastes bitter. These examples clearly demonstrate the importance of the use of homochiral compounds. 

Odier dragp are taken 1 hour before or 4 to 6 hours after cholestyramine Cholestyramine is available combined widi die artificial sweetener, aspartame (Questran Light), for patients widi diabetes or diose who are concerned with weight gain. 

The artificial sweetener aspartame is the low-calorie sweetener of choice at the time of this writing, having replaced cycla-... 

C13-0115. The artificial sweetener aspartame (NutraSweet) is Ihe methyl ester of Ihe following dipeptide ... 

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). 

In this present work, an alternative PLS-2 method was investigated and applied to the determination of sodium benzoate (itsed for preservatives) artificial sweeteners Aspartame, Acesitlfame-K and caffeine in diet cola drinks. 

PLS-UV Spectrophotometric Method for the Simultaneous Determination of Ternary Mixture of Sweeteners (Aspartame, Aeesulfame-K and Saeeharin) in Commereial Produets... 

Phenylalanine (Phe or F) (2-amino-3-phenyl-propanoic acid) is a neutral, aromatic amino acid with the formula HOOCCH(NH2)CH2C6H5. It is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. Tyr and Phe play a significant role not only in protein structure but also as important precursors for thyroid and adrenocortical hormones as well as in the synthesis of neurotransmitters such as dopamine and noradrenaline. The genetic disorder phenylketonuria (PKU) is the inability to metabolize Phe. This is caused by a deficiency of phenylalanine hydroxylase with the result that there is an accumulation of Phe in body fluids. Individuals with this disorder are known as phenylketonurics and must abstain from consumption of Phe. A nonfood source of Phe is the artificial sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester), which is metabolized by the body into several by-products including Phe. The side chain of Phe is immune from side reactions, but during catalytic hydrogenations the aromatic ring can be saturated and converted into a hexahydrophenylalanine residue. ... 

The other source of modem dmgs was the European dyestuff industry of the nineteenth and early twentieth centuries. The goal of this industry was to make useful dyes, principally for fabrics. In the course of handling novel molecules, scientists occasionally make unexpected observations (serendipity) that suggest novel utilities. For example, the commonly used sweetener aspartame was discovered by accident when a scientist licked a finger containing a bit of this substance. It turned out to be surprisingly sweet. 

The artificial sweetener cyclamate was banned because of a study linking it to bladder cancer in rats when large doses were fed. At least 20 subsequent studies have failed to confirm this result but cyclamate remains banned. In 1977 saccharin was found to cause cancer in rats. It was banned by the FDA temporarily, but Congress placed a moratorium on this ban because of public pressure. In 1992 it was found that saccharin may cause cancer in rats but not in humans. Saccharin is still available today. A more recent sweetener, aspartame (Nutrasweef ), has also come under attack but has not been proven to be a problem since its introduction in 1981. 

N and O function into the molecule and has been used to prepare hydroxyarginines (136,137), hydroxyornithines (136-138), p-lysine, p-leucine, and p-phenyl-p-alanine (139,140), the low-calorie sweetener aspartame (141) and the antitumor antibiotic acivicin (142-144). 

Apart from pharmaceuticals, peptides are also used for diagnostics and vaccines. More than 40 peptides are in commercial use today. A dozen of them is shown in Table 3.1. As shown in column 3 of the table, the number of amino acids that make up a specihc peptide varies widely. At the low end there are dipeptides, like the blockbuster antihypertensive drug enalapril and the artihcial sweetener Aspartame (not shown in the table). In terms of volumes produced, there are by far the most important product group. At the high end there is the anticoagulant Hirudin, which is composed of 65 amino acids. Sales of synthetic peptides are estimated at 4 billion as formulated drugs (resp. 300- 400 million as APIs). 

Nevertheless, one process for synthesis of the low calorie sweetener, Aspartame, which is a methyl ester of a dipeptide, (Asp-Phe-OMe) involves a biocatalytic step. Aspartic acid amino protected by benzyloxycarboi rl group, is reacted with two moles of phenylalanine methylester catalysed by the protease thermolysin. The extra mole of ester makes the dipeptide precipitate and it is later recycled. For details see section 4.6. 

Aspartic acid has been used in pharmaceuticals and foods etc. for some time, for instance as an acidulant. More recently, demand has been stimulated because it is a component of the dipeptide high intensity sweetener aspartame. 

Problem 21.25 (a) The artificial sweetener aspartame is a synthetic dipeptide. Asp.Phe. How many stereo-mers can aspartame have (b) Which isomer would result if naturally occurring amino acids were used ... 

Nowadays a wide variety of food ingredients are already produced in an encapsulated form. These comprise artificial sweeteners (aspartame), flavouring agents such as oils or spices (with desirable flavour but possibly undesirable odour), natural colorants (e.g., p-carotene, turmeric), preservatives, acids (citric, lactic and ascorbic), bases, buffers, enzymes, lactic acid bacteria, and some antioxidants (Kirby, 1991 Gibbs et al, 1999 Chen et al, 2006b Ubbink and Kruger, 2006 Augustin and He-... 

Phenylketonuria was among the first inheritable metabolic defects discovered in humans. When this condition is recognized early in infancy, mental retardation can largely be prevented by rigid dietary control. The diet must supply only enough phenylalanine and tyrosine to meet the needs for protein synthesis. Consumption of protein-rich foods must be curtailed. Natural proteins, such as casein of milk, must first be hydrolyzed and much of the phenylalanine removed to provide an appropriate diet, at least through childhood. Because the artificial sweetener aspartame is a dipeptide of aspartate and the methyl ester of phenylalanine (see Fig. l-23b), foods sweetened with aspartame bear warnings addressed to individuals on phenylalanine-controlled diets. 

Homogeneous asymmetric hydrogenation is a practical synthetic method (27). The DIPAMP-Rh-catalyzed reaction has been used for the commercial production of (S)-DOPA [(5)-3-(3,4-dihydroxy-phenyl) alanine] used to treat Parkinson s disease (Monsanto Co. and VES Isis-Chemie) (Scheme 12) (27, 28). (S)-Phenylalanine, a component of the nonnutritive sweetener aspartame, is also prepared by en-antioselective hydrogenation (Anic S.p.A. and Enichem Synthesis) (29). A cationic PNNP-Rh(nbd) complex appears to be the best catalyst for this purpose (15c) (see Scheme 5 in Chapter 1). 

M.9 In a combustion analysis of a 0.152-g sample of the artificial sweetener aspartame, it was found that 0.318 g of carbon dioxide, 0.084 g of water, and 0.0145 g of nitrogen were produced. What is the empirical formula of aspartame The molar mass of aspartame is 294 g-mol. What is its molecular formula ... 

JC Scherz, JC Monti, R Jost. Analysis of the peptide sweetener aspartame by liquid chromatography. Z Lebensm Unters Forsch 177 124-128, 1983. 

In the United Kingdom, intense sweeteners can be described on ingredient listings as Sweetener (name) (e.g. Sweetener aspartame ) or sweetener E-number ... 

Ingredients Carbonated water. Concentrated fruit juices (pineapple, grapefruit) (5% when reconstituted). Citric acid. Acidity regulator (sodium citrate). Artificial sweeteners (aspartame, saccharin). Flavourings. Preservative (sodium benzoate). Antioxidants (ascorbic acid, ascorbyl palmitate). Colour (lutein)... 

Paradoxically, the nutritional component of greatest commercial significance is the absence of nutrition, achieved by substituting carbohydrate sweeteners with non-nutritive sweeteners such as saccharin and acesulfame-K, or the amino acid sweetener aspartame. 

The food industry is a fertile area for biocatalysis applications high-fructose corn syrup (HFCS) from glucose with glucose isomerase, the thermolysin-catalyzed synthesis of the artificial sweetener Aspartame , hydrolysis of lactose for lactose-intolerant consumers, and the synthesis of the nutraceutical i-camitine in a two-enzyme system from "ybutyrobetaine all serve as examples. 

This approach enables high peptide yields in equilibrium-controlled peptide synthesis in high-density aqueous media with an equimolar supply of substrates. Scale-up to molar amounts verified the concepts as well as demonstrate the synthetic utility of this approach Z-His-Phe-NH2 and Z-Asp-Phe-OMe, precursors for cyclo-[-His-Phe-] and the low-calorie sweetener Aspartame, respectively, were synthesized in preparative yields of 84-88% (Eichhom, 1997). For a review of the field of peptide synthesis in unusual media, see Jakubke (1996). 

An example of a nonoccupational exposure is methanol, which is formed endogenously, probably as the result of the activities of intestinal flora or enzymatic processes. It is present in a number of consumer products. Methanol may be present in low concentrations in some foods, juices, and alcoholic beverages. Methanol can also be derived from the intestinal enzymatic hydrolysis of the artificial sweetener aspartame, which results in methanol absorption from the intestine (Butchko et al. 2002). It is estimated that a 355-mL serving of aspartame-sweetened beverages and of various fruit and tomato juices may contribute about 20-100 mg of dietary methanol (Butchko et al. 2002). For comparison purposes, exposure at the current Threshold Limit Value time-weighted average of methanol (262 mg/m3) would result in a daily dose of about 1,500 mg, assuming an 8-hour inhaled volume of 10 m3 of air and absorption of 57%. 

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