Sucralose from sucrose

Sucralose, Developed in England during the mid-1980s, testing and evaluation commenced in 1988. The structural formula of the compound (a chlorinated disaccharide derived from sucrose) is shown below. 

The sweetener aspartame was discovered in 1965 and approved by the FDA in 1981. It is the methyl ester of a dipeptide formed from the amino acids aspartic acid and phenylalanine. Because both of these amino acids occur naturally and arc part of nearly every protein, there is much less reason to be concerned about the health effects of this compound. Nevertheless, it has been extensively tested. Aspartame is about 180 times sweeter than sucrose, so the amount that is needed to sweeten a can of a soft drink, for example, is so small that it contributes only negligible calories to the diet. In addition, the taste profile of aspartame is much closer to sugar than is that of saccharin. Aspartame, sold under the brand name NutraSweet, has been an enormous financial success. Sucralose (Splenda) is prepared from sucrose by replacing some of the hydroxy groups with chlorines. Its taste closely resembles sucrose, but it is about 600 times sweeter. Acesulfame K (Sunett, Sweet One) is about 200 times sweeter than sucrose. It is quite stable to heat, so it is potentially very useful in baked goods. 

Fig. 9 Straightforward and efficient reaction pathway from sucrose to sucralose. R = Ac or Bz. (a) Organotin-mediated selective acylation 1. Starmoxane ester formation, 2. Acylation, (b) Selective chlorination by Vilsmeier type reaction DMF/acid chloride/AT. (c) Deacylation basic condition (e.g., NaOMe/MeOH)...

Note that sucralose (marketed under the trade name Splenda) differs from sucrose in the substitution of chlorine for three hydroxyls. 

Scheme 9.3.6 Short and efficient reaction pathway from sucrose to sucralose.

Following is the structure of the artificial sweetener sucralose. Indicate all the ways in which it differs from sucrose. 

Sucralose, which is known as Splenda, is made from sucrose by replacing some of the hydroxyl groups with chlorine atoms. 

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. 

Finally, a valuable example of multistep modifications of sucrose is the synthesis of Sucralose (l Ab -trideoxy-l Ab -trichloro-tya/flcm-sucrose)—a compound 650 times more sweeter than sucrose,15,326,327 which was obtained by treatment of 6-O-acetylsucrose with sulfuryl chloride in pyridine. Further reaction of this derivative with triphenylphosphine and diethyl azodicarboxylate afforded an epoxide from which a tetrachloro-derivative... 

Reaction of the artificial sweetener sucralose (being 650 times sweeter than sucrose) with triphenylphosphine and diethyl azodicarboxylate afforded epoxide 102 from which the tetra-chloro-derivative 103 was obtained (O Fig. 25) [72]. 

The low cost of sucrose makes it an attractive synthetic precursor for a wide range of applications (56), and a chlorinated derivative (l,6-dichloro-6-deoxy-(3-D-fructofuranosyl 6-chloro-4,6-dideoxy-a-D-galactopyranoside, sucralose) is widely used as a noncaloric sweetener (Splenda ). Various other oligosaccharides occur naturally in the free form (57), but far more have been isolated as fragmentation products from larger biomolecules their chemical or enzymatic synthesis is a very active current area of research, as detailed in Chapters 3 and 4. 

The most familiar of all sugars is sucrose—the mixed acetal formed from glucose and fructose. Sucrose is of course sweet, and is easily metabolized into fats. But if three of the OH groups in sucrose are replaced by chlorine atoms, a compound 600 times as sweet is produced less of it is needed to get the same sweet taste and the chlorines reduce the rate of metabolism so that much less fat is made. This is the compound sucralose, discovered by chemists at Tate Lyle and now used to sweeten soft drinks. 

There are a number of sugar substitutes, or artificial sweeteners on the market the most popular are saccharin, aspartame, sucralose, and cyclamate. Many of these were discovered by accident, when a chemist did something you re never supposed to do in a chemistry lab - lick your fingers. In the case of sodium cyclamate, the graduate student had put his cigarette on the side of the lab bench (yes, you were allowed to smoke in chemistry labs in 1937 ), and when he put it back in his mouth it tasted sweet. The advantage of these artificial sweeteners comes from the fact that they are often many times as sweet as sucrose, which means you don t need to use very much of them, and also that they are not metabolized in the same way as sugar, so you don t get fat. They also don t cause tooth decay. 

The newest frontier in sweetener research is the area of sweet enhancers. These substances, while tasteless themselves, cause sweetness receptors to respond more strongly to sweet substances. For example, the simple experimental molecule dubbed SE-2 enhances the sweetness of sucralose up to eightfold. It is thought that SE-2 and related structures bind to the Venus flytrap complex at a remote site from the sweetener itself, causing the trap to stay shut for longer periods of time. Sucrose and sucralose enhancers are beginning to be commercialized around the... 

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