Neotame

Neotame is the generic name for A-[A-(3,3-dimethylbutyl)-L-a-aspartyl]-L-phenylalanine-1-methyl ester. It is a derivative of aspartame and is a white powder. It is approximately 8000 times sweeter than sucrose and is, therefore, used at extremely low levels in soft drinks (e.g. 6 ppm in cola) (Prakash el al., 2002). 

Neotame is characterised by an intensely sweet taste with a lingering liquorice back-taste, which is more noticeable when it is used as a sole sweetener or at high levels. Combinations with other bulk and intense sweeteners improve the taste quality. Generally, acceptable products can be made without major reformulation using up to 25% of sweetener provided by neotame (The NutraSweet Company, 2003). 

Neotame is an amino acid derivative and is, therefore, hydrolysed under conditions of low or high pH. Its stability will be a function of pH, temperature and time. The optimum pH range is similar to that for aspartame pH 3.2 1.5. In dry form neotame is stable. Products containing neotame and processed by high-temperature short-time (HTST) do not show significant losses to degradation of neotame (The NutraSweet Company, 2003). 

Neotame is reported to have some flavour-enhancing properties, for example, of mint. It is rapidly metabolised by the body, yielding de-esterified neotame and small amounts of methanol. It does not accumulate in the body and is eliminated via the urine and faeces. Owing to its structure, L-phenylalanine is not a metabolite and, therefore, a PKU (phenylketonuria) statement is not required. No ADI has been assigned (The NutraSweet Company, 2003). 

In the United States the FDA granted general use approval for neotame as a sweetener and flavour enhancer in July 2002. At the time of writing it is also approved in Australia, New Zealand, China, Mexico, Costa Rica and Puerto Rico. Neotame was submitted to the EU SCF in 2001 for evaluation and to date no evaluation has been published. Poland has granted temporary approval for neotame and it is also approved in the Czech Republic and Romania. 

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Neotame is an artificial sweetener designed to overcome some of the problems with aspartame. The dimethylbutyl part of the molecule was added to block the action of peptidases, enzymes that break the peptide bond between the two amino acids aspartic acid and phenylalanine. This reduces the availability of phenylalanine, eliminating the need for a warning on labels directed at people who cannot properly metabolize phenylalanine. 

Neotame does not break down with the heat of cooking, another drawback to aspartame. It is also thirty times sweeter than aspartame, so less is needed to sweeten a product. 

Neotame is about eight thousand times sweeter than sugar, so only 6 milligrams is needed to sweeten a typical 12-ounce soft drink. 

Neotame is used in tabletop sweeteners, frozen desserts, chewing gum, candy, baked goods, fruit spreads, and ready-to-eat cereals. 

Food Additives Permitted for Direct Addition to Food for Human Consumption Sucralose. Federal Register August 12,1999 (Vol. 64, No. 155), http //class.fst.ohio-state.edu/fst621/Lectures/neotame.htm... 

Neostigmine bromide, 4 360t Neotame, 12 42 24 231-232, 247 NEP1 gene, 13 351 Nepetalactone, 2 101 24 473 Nepheline, 2 345t... 

One of the most efficient methods for oxidation of primary alcohols to either aldehydes or carboxylic acids is the one, commonly known as the Anelli oxidation. This reaction is carried out in a two-phase (CH2Cl2/aq.buffer) system utilizing TEMPO/NaBr as a catalyst and NaOCl as the terminal oxidant The new system described here is an extension of the Anelli oxidation, but surprisingly, does not require the use of any organic solvents and replaces the KBr co-catalyst with the more benign, Na2B40y (Borax). The use of the new cocatalyst reduces the volume of the buffer solution and eliminates completely the need of a reaction solvent. The new system was successfully applied in the industrial synthesis of the 3,3-Dimethylbutanal, which is a key intermediate in the preparation of the new artificial sweetener Neotame. 

In some cases, yeast preparations which contain a high amount of nucleotides can be used to increase saltiness in combination with masking ofiF-notes of KCl [30]. Additionally, use of low amounts of fruit acids may reduce the bad taste of KCl-containing food preparations [31]. Usage of low amounts of sweeteners such as thaumatin [32] or neotame [33] was described to mask the ofiF-taste of KCl. 

Formulators in most markets now have a wide range of sweeteners available to use either alone or in combination. As Figures 4.1 and 4.2 show, the main intense sweeteners in use in soft drinks today are acesulfame K, aspartame, saccharin and cyclamate. Currently of less importance commercially (either because they are new to the market or because they have not found significant use in soft drinks), but still approved for use in soft drinks in some markets, are thaumatin, neohesperidin diliy-diochalcones, alitame, stevioside, sucralose and neotame. 

The NutraSweet Company (2003) Neotame Technical Brochure, The NutraSweet Company, Chicago, II. 

When attempting quantitation of a mixture of polymorphs, the first step is to identify which peaks are due to each polymorph, and to select two well-resolved peaks corresponding to the same carbon in each polymorph. A multiple-contact time experiment is then acquired to determine the rates of magnetization transfer (7ch) and decay (Tip) for each form. If these rates are identical in each form, direct integration of the peaks will provide quantitative data, with the relative areas representing the amount of each form present in the mixture. An example of the results of a multiple-contact time experiment is shown in Fig. 2—a plot of the natural logarithm of relative peak area as a function of contact time for neotame forms A and It is clear from this plot that spectra acquired at any contact time will not give equal peak area for both forms. 

Fig. 2 Plot of the results of a multiple-contact time experiment of neotame polymorphic forms A and G showing buildup and decay of magnetization as a function of contact time. (From Ref. l)...

Fig. 3 CPMAS NMR spectrum of a 1 1 (wt/wt) mixture of neotame forms A and G. Inset shows expansion of the peaks used for quantitation, representing the same aromatic carbon in each polymorph. Relative peak areas are shown. (From Ref 1)...

Gao described the use of CPMAS NMR to quantitate binary mixtures of crystalline forms of dela-virdine mesylate, with calculated limits of detection (LODs) of 1-1.5% and observed LODs of 2-3%. Mass fractions ranging from 2%i to 50%i of the minor component were analyzed, and a linear correlation was found between the calculated and NMR-measured values. The methods used here, similar to those described above for neotame, benefit from the fact that no calibration curve or internal standard is needed however. 

Table 1 Quantitation data for mixtures of neotame forms A and G...

Offerdahl, T.J. Salsbury, J.S. Dong, Z. Grant, D.J.W. Schroeder, S.A. Prakash, I. Munson, E.J. Quantitation of crystalhne and amorphous forms of neotame using C CPMAS NMR spectroscopy. J. Pharm. Sci. Submitted for publication. 

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