Non-nutritive, sweeteners

The isothiazole ring does not occur in nature. By far the most important synthetic isothiazole derivative is saccharin. This was the first non-carbohydrate sweetening agent to be discovered, as long ago as 1879. It is about 300 times as sweet as sucrose, and is still used in many countries as a non-nutritive sweetener. After it was found that administration of massive doses to rats caused bladder cancer, its use was banned in the New World, but the controversy continues as to whether there is any danger when it is used in small quantity. Saccharin is also used as an additive in electroplating processes (73AHC(15)233). 

The non-nutritive sweeteners stand out because they are so much sweeter than sugar. 

Saccharin is a non-nutritive sweetener used in toothpastes, cold remedies, ice creams, and coffee-sweetening packets. Its use in soft drinks has been almost entirely replaced by aspartame. 

Did you know the average American consumes the equivalent of 20 teaspoons of sugar each day The non-nutritive sweetener industry is described as a billion-dollar industry with projections of even more rapid expansion in the next few years. What do chemists look for in their search for an ideal sweetener Consumers seek good-tasting, nontoxic, low-caloric sweeteners. Chemists in the sweetener industry add further demands an inexpensive, easy-to-synthesize product that is readily soluble in water and resists degradation by heat and light is of prime importance. The chemical structure of sucralose keeps the sweetener intact as it passes through the acidic environment of the stomach. Thus, sucralose is not... 

NMR, protein structure determination, 23, 275 non-enzymatic glycosylation, 14, 261 non-HIV antiviral agents, 36, 119, 38, 213 non-nutritive, sweeteners, V7, 323 non-peptide agonists, 32, 277 non-peptidic d-opinoid agonists, 37,159... 

That no risk exists can he proved under one and only one set of circumstances when it is certain that exposure does not exist. How can the latter condition he ensured The only real way is to guarantee that a chemical is not used for any purpose. We can know that exposure to cyclamate, a commonly used non-nutritive sweetener until 35 years ago when it was banned by the FDA, does not exist (save, perhaps, in somebody s laboratory, where a few bottles might be sitting around, and in some other countries, where its use is permitted), because food manufacturers are prohibited from adding it to foods and beverages. Cyclamate thus poses no risk to individuals in the United States -under present conditions we are absolutely protected from any risks this chemical may pose (a debate still continues about whether it is carcinogenic but that is irrelevant to this discussion). 

The FDA also regulates food additives - substances, such as antioxidants, emulsifiers and non-nutritive sweeteners, that are intentionally and directly added to food to achieve some desired technical quality in the food. As noted, the Delaney clause prohibits the deliberate addition to food of any amount of a carcinogen. These additives, if they are threshold agents (not carcinogenic), can be allowed as long as the human intake does not exceed a well-documented ADI. Those who would seek approval for an additive need to supply the FDA with all of the toxicity information needed to establish a reliable ADI, and all of the product-use data that would permit the agency to assure itself that the ADI will not be exceeded when the additive is used. 

Every patient with diabetes requires some form of dietary assessment, and often therapy. This is important to allocate the relative amounts of energy derived from carbohydrate, protein and fat of total recommended daily calories in proportion to the patient s body weight and height and daily requirements, while avoiding atherogenic diets. Diets with high carbohydrate content (50-60%), low fat (30-35%) and adequate protein (10-15%) is recommended. Fibre-rich foods are preferable. The use of non-nutritive sweeteners (saccharin, aspartame, ace-sulfame K and sucralose) are acceptable. Alcohol intake should be assessed since excess consumption... 

Lactitol. Lactitol (4-0-/ -D-galactopyranosyl-D-sorbitol), is a synthetic sugar alcohol produced on reduction of lactose, usually using Raney nickel. It can be crystallized as a mono- or di-hydrate. Lactitol is not metabolized by higher animals it is relatively sweet and hence has potential as a non-nutritive sweetener. It is claimed that lactitol reduces the absorption of sucrose, blood and liver cholesterol levels and to be anticariogenic. It has applications in low-calorie foods (jams, marmalade, chocolate, baked goods) it is non-hygroscopic and can be used to coat moisture-sensitive foods, e.g. sweets. 

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. 

A first prototype can then be put together with the decided carbohydrate system and with salts added to approximate to the target electrolyte levels. Sweetness must be adjusted, probably by adding non-nutritive sweetener(s), an acidity level must be selected and flavour, colour and preservative must be added at appropriate levels. If the drink is to be carbonated a level must be chosen (a low level is preferable). 

International Agency for Research on Cancer, IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Some Non-nutritive Sweetening Agents, Vol. 22, pp. 64-109, Lyon, France, 1980. 

Carter, E.B., S.L. Culver, P.A. Fox, R.D. Goode, I. Ntai, M.D. Tickell, R.K. Traylor, N.W. Hoffman and J.H. Davis Jr., Sweet Success Ionic Liquids Derived from Non-Nutritive Sweeteners, Chemical Communications, 630-631 (2004). 

In the past, ketose-type pyranose carbasugars were mainly investigated in the search for sucrose mimics to employ as non-nutritive sweeteners [25a,b]. Probably due to this seemingly unappealing potential and the inherent difficulties related to their stereoconstitutional features, up until 1990 only one report was found to have been published dealing with the asymmetric synthesis of D- and L-carba-analogues of fructopyranose [34]. 

Enantioselective catalytic hydrogenation. Hoffmann-LaRoche chemists have examined the efficiency of DIOP (1) and a number of related phosphines as ligands for asymmetric hydrogenation of acrylic acids for synthesis of (R)-6-methyl-tryptophan (6), of potential value as a non-nutritive sweetening agent. Of these, 2 and the less available 3 showed the most promise. Thus catalytic hydrogenation of 4... 

FAOAVHO. Specifications for the identity and purity of food additives and their toxicological evaluation some flavouring substances and non-nutritive sweetening agents. Eleventh report of the Joint FAOAVHO Expert Committee on Food Additives. 

DuBois GE, Crosby GA, Saffron P. Non-nutritive sweeteners taste-structure relationships for some new simple dihydrochalcones. 

Carter E B, Culver S L, Fox P A, et al. Sweet success Ionic hquids derived from non-nutritive sweeteners. Chem. Commun. 2004. 6, 630-631. 

The sulfur derivative (87) is 1000 times as sweet as sugar and without the bitter after-taste of saccharin however, it was discovered that N-alkylation of (87) removed the sweetness. On the other hand, in the saccharins (88a)-(88e) containing substituents in the 4-position and 6-position, sweetness was retained after N-alkylation. Many sulfamic acid derivatives are sweet, and there have been numerous studies of structure-taste relationships which have highlighted the importance of molecular shape and stereochemistry (see Chapter 9, p. 162). Two sulfamates which are commercial, non-nutritive sweeteners are cyclamate (85) and acesulfame potassium (86) (Figure 11). Cyclamate (85) is manufactured by refluixing cyclohexylamine either with triethylamine-sulfur trioxide in dichloromethane or with sulfamic acid (see Chapter 9, p. 162). 

Jeffrey AM and Williams GM (2000) Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repair assay. Pood and Chemical Toxicology 38 335-338. 

Sodium chloride/salt Sodium nitrite Sodium/potassium nitrate Monosodium glutamate/MSG/Vetsin specific name for non-nutritive sweeteners... 

The once widely used non-nutritive sweetener, saccharin, produces... 

An illustration of the second strategy is provided by the para-cyano analogs of the non-nutritive sweetener suosan (Figure 41.18). The replacement of the planar carboxylic group by the bioisosteric tetrazolyl group yields less potent, but still sweet compounds. ... 

The non-nutritive sweetening properties of the salts of certain aliphatic and alicyclic sulphamic acids are well known. DuBois235 considered that the sulphamic acid salt (215) of the dihydrochalcone (216) should be sweet. Known sulphamation methods of 217... 

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