Synthesis and bacterial metabolism of cis- and trans-2-alkyl analogues of sodium cyclamate.
Sodium cyclamate is an effective artificial sweetner, which has been banned from the U.SD. market because of alleged carcinogenic properties. It appears that cyclohexylamine, liberated from cyclamate as a result of bacterial mtabolism, is the proximate carcinogen. In an effort to elucidate the extent to which analogues of cyclamate would enter into the bacterial metabolic pathway, as well as any stereochemical requirements which might exist, several 2-alkaly analogues of sodium cyclamate were prepared. It was found that trans-N-(2-methylcyclohexyl)sulfamate (trans-2a) and trans-N-(2-ethylcyclohexyl)sulfamate were hydrolyzed by freshly collected fecal suspensions from rats fed cyclamate, but not from control rats, at the same rate as cyclamate itself. trans-N-(2-Isopropylcyclohexyl)sulfamate (trans-2c) was not hydrolyzed at all. Surprisingly, two of the analogous cis compounds (cis-2a and cis-2c, respectively) were hydrolyzed by fecal suspensions from control, as well as from cyclamate-fed, rats. Moreover, cis-2a was hydrolyzed by incubating it in medium only. Thus, it is apparent that stereochemical influences on the chemical properties of these compounds are substantial. These results do not appear to point the way toward a safe, nonmetabolizable sweetening agent.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003494:Cyclamates / Q000138:chemical synthesis* / Q000378:metabolism; D005243:Feces / Q000032:analysis; D007202:Indicators and Reagents; D007536:Isomerism; D051381:Rats; D013329:Structure-Activity Relationship; D013549:Sweetening Agents / Q000378:metabolism
D003494:Cyclamates; D007202:Indicators and Reagents; D013549:Sweetening Agents