Synthesis and taste properties of sodium monosubstituted phenylsulfamates

Quantitative Structure−Activity Relationship Studies of Sulfamates RNHSO3Na: Distinction between Sweet, Sweet-Bitter, and Bitter Molecules

“…As k w was experimentally determined, it was decided to use it preferentially in this study. Among the sweet-bitter group of compounds, 22-32 and 36-41 have been synthesized and assessed for taste quality (sweet, bitter, sour, salty) previously (Spillane et al, 1993(Spillane et al, , 1994. Compounds 33-35 have been synthesized in this work, and their taste assessment places them in the sweet-bitter category (see Experimental Procedures).…”

“…The taste panel procedure for assessing the taste quality of 33-35 has been described in detail in earlier work (Spillane et al, 1994). In the present work six trained assessors were used, and the following are the percentages of assessors giving the tastes sweet, sour, bitter, salty, tasteless, and sweet aftertaste: 33, 0, 0, 100, 0, 0, 100%; 34, 0, 0, 100, 0, 0, 60%; and 35, 0, 0, 100, 0, 0, 80%.…”

“…The main thrust of QSAR studies has been in the field of drug design, but there have been several applications to the taste properties of molecules, particularly involving sweetness. The main groups of sweeteners that have been subjected to various types of QSAR studies are the nitro-and cyanoanilines (Deutsch et al, 1966;McFarland, 1971;Holtje and Kier, 1974;Iwamura, 1980;Kier, 1985;van der Heijden et al, 1985a), various aspartyl dipeptide derivatives (van der Heijden et al, 1979(van der Heijden et al, , 1985aIwamura, 1981;Miyashita et al, 1986a), oximes (perillartines) (Iwamura, 1980;van der Heijden et al, 1985b;Acton et al, 1976;Takahashi et al, 1982Takahashi et al, , 1984Zalewski, 1992), β-(3-hydroxy and 4-methoxyphenylethylbenzenes (Miyashita et al, 1989), acesulfames, tryptophans, saccharins, chlorocarbohydrates, ureas, isocoumarins (van der Heijden, 1985a, and sulfamates (Spillane and McGlinchey, 1981;Spillane et al, 1983Spillane et al, , 1994Miyashita et al, 1986b;Okuyama et al, 1988). For the latter group, which includes cyclamate (N-cyclohexylsulfamate), we have previously developed semi-QSARs using parameters measured with Corey-Pauling-Koltun (CPK) space-filling models of the R section of the sulfamates RNHSO 3 Na.…”

“…For the latter group, which includes cyclamate (N-cyclohexylsulfamate), we have previously developed semi-QSARs using parameters measured with Corey-Pauling-Koltun (CPK) space-filling models of the R section of the sulfamates RNHSO 3 Na. This approach has been successful for carbosulfamates (Spillane and McGlinchey, 1981; and monosubstituted aromatic sulfamates (Spillane et al, , 1994 and has shown good predictive ability. A pattern recognition method (Miyashita et al, 1986a,b;Ikuyama et al, 1988), discriminant analysis and principal component analysis (PCA) (Zalewski, 1992), and use of STERIMOL parameters (van der Heijden et al, 1985a,b) have been employed to develop structure-taste relationships for the carbosulfamates.…”

“…Values of k w were experimentally measured using reversed-phase HPLC (see Experimental Procedures). Corey-Pauling-Koltun volumes (V CPK ) were measured as described previously (Spillane et al, 1994). Thirdorder molecular connectivities ( 3 χ m ) were calculated using the method of Kier and Hall (1976).…”