Synthesis of Supersweet Sucroses

6 -dichloro-6,6 -dideoxysucrose can be synthesized in high yields ( 70%) by reaction of sucrose with triphenylphosphine in carbontetrachloride and pyridine [28] (see reaction 4.123 in Chapter 4). It, however, is not sweet at all. The 4,6,r,6 -tetrachloro-4,6,r,6 -tetradeoxygalactosucrose was first synthesized by preparing the 6,r,6 -tri-0-(methylphenylsulfonyl) sucrose, followed by reaction with lithium chloride and chlorination of the C-4 hydroxyl with sulfuryl chloride [27] (see Fig. 5.7B). This tetrachlorogalactosucrose was found to be 200 times sweeter than sucrose. 

An even sweeter chlorodeoxysucrose was later synthesized by the reaction of sucralose with triphenylphosphine and diethyl azodicarboxylate to give the 3, 4 -lyxo epoxide, followed by stereospecific opening of the epoxide with chloride to 

Hough and Khan [30] concluded that the I -chloro (halo) substituent on the fructose moiety was critical for an intense sweet taste. Addition of chlorine to the 

C-6 and C-4, with inversion, provided an additional increase in the sweetness. Addition of chlorine to the C-6 position was deleterious to the sweet-tasting character. The substitution at C-4, with inversion, produced compounds that were sweeter than those substituted at C-4, with retention of the configuration. Inversion of the C-4 hydroxyl to give galactosucrose, however, formed a compound that was devoid of sweetness. Hence, the substitution of a chlorine atom, with inversion, significantly contributed to the sweetness. 

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