Sucralose synthesis

Since its first synthesis, optimizations of the detailed reaction sequence have been carried out during the past decades finally leading to a bundle of patents covering diflerent possibilities to execute this reaction cascade." " Out of these patents a rather straightforward sucralose synthesis could be assembled (Scheme 9.3.6), the first step of which is a dibutyltin-oxide-supported selective... 

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... 

T. Tsuchiya and S. Umezawa, Studies of antibiotics and related substances. XXI. The synthesis of deoxy and chlorodeoxy derivatives of kanamycin. Bull. Chem. Soc. Jpn. 38 1181 (1965). T, Suami, L. Hough, M. Tsuboi, T. Machinami, and N. Watanabe, Molecular mechanisms of sweet taste. V. Sucralose and its derivatives, J. Carbohydr. Chem. 73 1079 (1994). 

Selective chlorination of sucrose, by which three of sucrose s hydroxyl groups are substituted with chlorine atoms, produces sucralose (l,6-dichloro-l,6-dideoxy- S-D-fructofuranosyl-(24>l)-4-chloro-4-deoxy-a-galactopyranoside) sweetener sold as Splenda [49]. Sucralose is approximately 650 times sweeter than sucrose and can be used in baking. Its synthesis involves treatment of a partially acetylated sucrose with sulfuryl chloride the initially formed chlorosulfate esters act as leaving groups and undergo nucleophilic displacement by chlorine [20]. Sucralose was first approved for use in Canada in 1991 as of 2006, it has been approved in over 60 countries. 

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. 

D-Sucralose is a trichloro derivative of sucrose whose structure is shown on page 490. This disaccharide is 600 times sweeter than sucrose and is sold under the brand name of Splenda . For a nice review of the synthesis and properties of commercial, synthetic nonnutritive sweeteners, see Angew. Chem. Int. Ed. 1998, 37,... 

Figure 5.7. Synthesis of intensely sweet chlorodeoxy sucroses A, Reaction of sucrose with sulfiiryl chloride in pyridine/chloroform at 0 dgC B, synthesis of 4,6,r,6 -tetra-chloro-4,64, 6 -tetradeoxygalactosucrose C, synthesis of 4,r,6 -trichloro-4,l, 6 -tri-deoxygalactosucrose (sucralose) D, synthesis of 4 -bromo-4,l, 4, 6 -tetradeoxygalacto-sucrose.

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