RESUMEN

The U and Gamma' models of sensory interactions, successfully applied in olfaction for several years, are tested here using data from published studies on sweetness. The models are subsequently tested on new data obtained in studies of binary mixtures of four sodium sulfamates. The U model allows for the estimation of a global interaction, whereas the Gamma' model allows for the distinction between that which is due to an intrinsic interaction in the mixture itself and that which may be due to the power function exponents in the mixture. The models give satisfactory predictions for observed phenomena of sweet taste suppression, synergism or pure additivity. Additionally, they appear to be more suitable than other models recently applied in taste, particularly the equiratio model. Application of the models to the sulfamate mixtures, reveals additivity for sodium cyclohexylsulfamate (cyclamate)/potassium cyclohexylsulfamate and sodium cyclohexylsulfamate/sodium exo-2-norbornylsulfamate, respectively; whereas for sodium cyclohexylsulfamate/sodium 3-bromophenylsulfamate, the models revealed a slight hypo addition which is simply due to the dissimilarity values of the power function exponents of the components.

Asunto(s)

RESUMEN

The kinetics of the reactions of the nitrogen-sulfur(VI) esters 4-nitrophenyl N-methylsulfamate (NPMS) with a series of pyridines and a series of alicyclic amines and of 4-nitrophenyl N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series of quinuclidines have been investigated in acetonitrile (ACN) in the presence of excess amine at various temperatures. Pseudo-first-order rate constants (k(obsd)) have been obtained by monitoring the release of 4-nitrophenol/4-nitrophenoxide. From the slope of a plot of k(obsd) vs [amine], second-order rate constants (k'(2)) have been obtained for the pyridinolysis of NPMS, and a Brønsted plot of log k'(2) vs pK(a) of pyridine gave a straight line with beta = 0.45. However, aminolysis with alicyclic amines of NPMS gave a biphasic Brønsted plot (beta(1) = 0.6, beta(2) approximately equal to 0). Pyridinolysis and aminolysis with alicyclic amines and quinuclidines of NPBS also gave similar biphasic Brønsted plots. This biphasic behavior has been explained in terms of a mechanistic change within the E1cB mechanism from an (E1cB)(irrev) (less basic amines) to an (E1cB)(rev) (more basic amines), and the change occurs at approximately the pK(a)'s (in ACN) of NPMS (17.94) and NPBS (17.68). The straight line Brønsted plot for NPMS with pyridines occurs because the later bases are not strong enough to substantially remove the substrate proton and initiate the mechanistic change observed in the reaction of NPMS with the strong alicyclic amines and quinuclidines. An entropy study supports the change from a bimolecular to a unimolecular mechanism. This is the first clear demonstration of this E1cB mechanistic changeover involving a nitrogen acid substrate.

Asunto(s)

RESUMEN

Eleven heterosulfamates have been synthesized, characterized, and evaluated for sweetness. Measurements of the molecular dimensions (x, y, z, and V) of these sulfamates and 22 others that had been reported previously and evaluated for sweetness have been made using Corey-Pauling-Koltun space-filling models. The first-order molecular connectivities (1Xv) of all the heterosulfamates have been calculated. The statistical technique of linear discriminant analysis was applied to the complete set of 33 compounds and to a reduced set of 27 compounds. The analysis was performed using the above five variables (x, y, z, V, and 1Xv) and various subsets thereof. For the complete set of compounds, seven variable subsets were identified which yielded correct classifications of 27 and 28 compounds. A similar analysis of the reduced set did not improve the misclassification rate.

Asunto(s)

RESUMEN

The sweet compounds 2-methyl- and 3-methylcyclohexyl- and 2-cyclohexenylsulfamates were fed to Wistar albino rats. The urine (and feces in the case of 2-cyclohexenylsulfamate) was examined for possible amine, ketone, and alcohol metabolites. The total percent of metabolites formed was low and the hexenyl compound gave a particularly small quantity of metabolite. The results with these compounds are compared with those obtained from earlier in vivo studies with cyclamate and other sulfamates. In complementary in vitro studies, the four sweetest sulfamates, namely, cyclamate, cycloheptyl-, cyclooctyl-, and cyclopentylsulfamates were incubated with the cell-free extract of bacteria isolated from the feces of cyclamate fed rats. Some correlation was apparent between these in vitro experiments and previous in vivo studies. Preliminary mutagenicity testing (the Ames test) of some amines (corresponding to the sulfamates studied) has been carried out.

Asunto(s)

RESUMEN

With the use of Corey-Pauling -Koltun space-filling models, measurements of defined parameters (x, y, and z) were made of the R groups in a large number of carbosulfamates, RNHSO-3. The correlation between sweet and nonsweet sulfamates and the defined parameters for R is good. As a test, 12 new carbosulfamates were synthesized and tasted. The predictions of their sweetness or nonsweetness based on the correlation were greater than 90% correct. To elicit a sweet taste, the R group of the sulfamate should have x greater than or equal to 5.2 A and less than or equal to 7.2 A and V (i.e.,xyz) less than or equal to 250 A3 and probably greater than or equal to 90 A3. The receptor site is seen (as for aspartame) as a rather narrow cleft into which R has to fit "properly" or be "locked" so that the AH,B mechanism for initiating the sweet stimulae can operate. Possible applications of this approach are indicated.

Asunto(s)

RESUMEN

The nonnutritive sweeteners cyclooctylsulfamate and 4-methylcyclohexylsulfamate were fed separately to female Wistar albino rats, and the urine was examined for the possible metabolites cyclooctylamine, cyclooctanone, cyclooctanol, 4-methylcyclohexylamine, 4-methylcyclohexanone, and cis- and trans-4-methylcyclohexanols. The average percent conversions to cyclooctylamine, cyclooctanone, and cyclooctanol were 0.127, 0.08, and 0.092, respectively. The average percent conversions to 4-methylcyclohexylamine and 4-methylcyclohexanone were 0.007 and 0.0013, respectively. No cis- or trans-4-methylcyclohexanol metabolites were found. With cyclooctylsulfamate, 42% was recovered unchanged from the urine. Cyclooctyl- and cycloheptylsulfamates were metabolized to a greater extent than cyclopentylsulfamate, which, in turn, was metabolized to a greater extent than cyclohexylsulfamate (cyclamate) and 4-methylcyclohexylsulfamate.

Asunto(s)

RESUMEN

The nonnutritive sweetener sodium cyclopentylmethyl-sulfamate was fed to Wistar albino rats. The urine was collected for 3 days, combined, and examined (GLC) for the metabolites cyclopentyl-methylamine and cyclopentylmethanol. The percent conversion to these metabolites was 0.077 and 0.0102, respectively. The percent conversion to these to cyclopentylmethylamine was the lowest conversion to amine observed when compared to the metabolism of three other sweet sulfamates, cyclopentylsulfamate, cycloheptylsulfamate, and cyclooctylsulfamate, previously administered to rats. The average excretion of unmetabolized sulfamate was 15.4%. Sodium cyclopentylsulfamate was fed to rats over 9 days, and an analysis was carried out for the metabolites cyclopentylamine, cyclopentanone, and cyclopentanol. A decrease in the level of metabolites occurred after the first 3 days.

Asunto(s)

Asunto(s)

RESUMEN

The nonnutritive sweetener cycloheptylsulfamate was administered orally to rabbits and rats. The urine of each species was separately collected for 3 days and examined for the metabolites cycloheptylamine, cycloheptanone, and cycloheptanol and for cycloheptylsulfamate. A previously tested GLC method was adapted for the determination of the metabolites. Cycloheptylsulfamate was assayed by hydrolysis and subsequent measurement of the absorbance of the product formed (lambdamax=489 nm) by the liberated amine with p-benzoquinone. The conversions to the metabolites were 0.276, 0.390, and 0.170%, respectively, in rabbits and 0.064, 0.022, and 0.017%, respectively, in rats.

Asunto(s)

RESUMEN

The nonnutritive sweetener sodium cyclopentylsulfamate was fed to Wistar albino rats and New Zealand White rabbits. Urine was collected for 3 days after feeding, combined, and examined for the metabolites cyclopentylamine, cyclopentanone, and cyclopentanol and for sodium cyclopentylsulfamate was assayed by hydrolysis in acidified dioxane-water and subsequent measurement of the absorbance of the product formed (lambdamax = 490 nm) by the liberated amine with p-benzoquinone. The average conversion to cyclopentylamine, cyclopentanone, and cyclopentanol was 0.103, 0.171, and 0.054% in the rabbit and 0.057, 0.016, and 0.008% in the rat, respectively.

Asunto(s)

Asunto(s)

RESUMEN

The structure-activity relationships governing sulfamate sweeteners are reviewed under the headings: size of the reduced ring, changes in the sulfamate function, substitution of hydrogen in the ring, and substitution of carbon in the ring and open-chain compounds. Fifteen compounds have been synthesized with a view to testing the limitations on structural changes which may be made within these categories without loss of sweetness. The presence of the grouping greater than CHN(R)SO3- is suggested as a necessary but not a sufficient condition for a compound to be sweet-tasting. Thus, the B center of the Shallenberger A-H,B theory of sweetness is best regarded as being -SO3- rather than -SO2- for sulfamates. Threshold levels and relative sweetness have been determined for seven sulfamates.

Asunto(s)

Asunto(s)