CA2117284A1 - Specific eatable taste modifiers - Google Patents

Abstract

2117284 9310677 PCTABS00022 Ingestible compounds which are substantially tasteless and which have been found to be effective reducers or eliminators of undesirable tastes for eatables.

Description

, SP~C~FIC EATABLE TASTE ~ODIFIERS

B~CKGROUND OF T~E INVENTION

This application i~ a continuation-in-part of application serial n~mber 07/799,207 filed November 27, l99l which in turn is a continuation-in-part of application serial number 07/531,388 filed June l, l990.
This invention relates in general to taste modifying compoun~s. More particularly it relates to tastands, as such term is used hereinbelow, to reduce or eliminate undesirable tastes~, as such term is used hereinbelow.
There are numerous compounds that are known to be salty but have problems associated with their use as salt substitutes. Potassium chloride has a pronounced strong bitter undesirable taste, as such term is used hereinbelow, and ammonium chloride has, at least as sensed in some people, a fishy taste a~sociated with it. Lithium chloride, although a somewhat better tasting salt, is highly toxic.
To date there is no universally ~atisfactory salty tasting substitute for the sodium ion.
The desirability of reducing the sodium ion intake of humans is well do~umented. An excessive intake of sodium ion has been linked to high blood pressure and premature heart attack.: This problem has been addressed by numerou~
researc~ers in:~a variety of ways ~er the pas~ tWQ decades.
At the current time, reduction of sodium ion intake is achieved via a:combination of ab~tinence a~d/or ~he substi~ution of potas~ium chloride for sodium chloride and/or mixing sodium chloride with fillers so that less sodium chloride i9 used on the eatable, as defined hereinbelow, although the volume of material added to the eatable is the sameO In addition, for materials that are coated with a surface salt such as for example potato chips, it is known that smaller particle size for the sodium chloride results in a saltier taste per~eption, and therefore less salt need be added to obtain an equal level of salt perception.

WO93/10677 CA 2 11 7284 pcr/usg2/lo179 There are a variety of products on the market today utilizing potassium chloride as a saltening agent. All of these salt substitutes rely on other ingredients which are mixed with the potassium chloride to mask the bitter undesirable taste, as such term is used hereinbelow, of potassium chloride. These highly flavorful ingredients consist of items such as onion, garlic, paprika, red pepper, chili powder and many other spices. None of these mixtures or potassium chloride itself has found wide-spread acceptance, probably because the bitter taste of potassium ion is still detectable.
In addition to reducing sodium ion intake by the substitution of sodium chloride by potassium chloride, there are numerous other examples of-compounds containing sodium ions used in the food industry which could benefit by the substitution of potassium ion for sodium ion if the bitter taste associated with potassium ion were eliminated.
For example, sodium baking soda or baking powder could be substituted with potassium baking soda and potassium baking powder, respectiYely, in products requiring leavening agents. A few more examples of substitutions which could be made are:
A. monopotass~ium glutamate for monosodium glutamate in the case of flavoring, and, B. potassium~nitrate or nitrite for the corre~ponding sodiu~ nitrate or nitrite in the case of preservatives,~and, C. potassium;~benzoate, potassium sulfate or sulfite in place of oorresponding sodium salts in the case of ~-~ preservatives would also be highly desirable.
~;~ In addition, numerous eatables, as defined hereinbelow,;on the market today have a naturally bitter taste and/or undesirable taste, as such terms are used hereinbelow.-Many of these materials, as currently used, have the bitter tas~e or aftertaste partially masked by additives, such as flavorings similar to those stated ~; above. Many of these materials are still bitter and/or still have an aftertaste and could benefit by having a tastand, as such term is used hereinbelow, mixed or W0~3~10677 C A 2 1 1 7 2 8 4 3 PCT~US92J10179 ingested along with them to eliminate or substantially reduce the undesirable taste(s), as such term is used hereinbelow. Such eatables as for example, pharmaceuticals, antibiotics, pain killers, aspirin, codeine, ibuprofen, acetaminophen, caffeine, and unsweetened chocolate, and ~weeteners, as such term is used hereinbelow, can have their undesirable tastes, as such term i8 used héreinbelow, `reduced and/or eliminated as well as having their palatability enhanced by the use of a tastand, as such term is used hereinbelow. In general, any eatable which has a naturally undesirable taste, as such term is used hereinbelow, should be able to be rendered more palatable by the addition of an appropriate tastand, as such term is used hereinbelow.
.
SUMMARY OF THE INVENTION

Differences in taste perception between individuals seem to be common. m ere are more than just the basic or "true" tastes of sweet, sour, bitter, umami, and salty. A
few examples of these other tastes a~e alkaline, astringent, tanl~y, dry,~sharp, cool, hot, burning, acidic, spicy, pungent, and/or~metallic.
As used herei~and in the appended claims, undesirable taste(s)" shall mean any taste which is sweet, bitter, sour,;alkaline, astringent, tangy, dry, sharp, cool, hot, burning, acidic, spicy, pungent, woody, smokey, umami and/or metallic. Such undesirable taste shall include any and all tastes, if such taste(s) is unwanted and include any and~all aftertaste(s), if such aftertaste is unwanted.
There can be more than one perception of a single taste, whether such taste is a "true" taste or another taste. There are;a number of different "bitter" tastes that can be noted by some individuals. This can be demonstrated by the following-Some tastands which reduce or substantially eliminate the off-taste of:
l. For example, caffeine, may have little or no ~`C~211;7~ 4 effect on a pharmaceutical and/or the off-taste of KCl, or,

2. For example, L aspartyl-~-phenylalanine methyl ester (Aspartamee) may have little or no effect on the off-taste of another high intensity swe~tener such as saccharin.
Some specific examples of these effects are:
A. L-Aspartyl-L-phenylalanine will have a substantial effect on the off-taste aæsociated with L-aspartyl-L-phenylalanine me~hyl ester (Aspartame ), while it has less effect on the off-taste associated with &accharin, B. Taurine has a substantial effect on the off taste of saccharin while it has little or no effect on the of~-taste associated with L-aspartyl-L-phenylalanine methyl ester (Aspartame~).
C. The burning after-taste associated with some liquors can be substantially ~liminated with the use of potaæsium 2,4-dihydroxybenzoate while ~-a~partyl-L
phenylalanin~ and taurine have considerably less of an :~
effect.
More specific examples of this effect are set forth in the following table. The concentrations ~ecessary to obtain these effects are~dependent upon the specific tastand and ~atarial and vary widely from example to exa~ple in the table. The effects ~mmarized in the table pr~vide a further indication of the existence of different bittsr taste6. Ihu5~ a6 illustrated, L-aspartyl-L-phenylalanine blocks t~e bitter~tas~e of KCl but has little effect on the bitterness a~so~iated with caffeine. In contra-~t, N-(p-cyanophenylcarbamoyl)-aminomethanesulfonic acid reduces the bitter taste of caffeine but is not effective against the : `
bitter taste of KCl. A plausible conclusion is that eparate receptors and/or independent sites on one or more ~: ' ::

WO93/lOG77 ~ A ~ 1 1 7 2 ~ 4 PCT/US92/10179 receptor are involved in the bitter taste sensation.
. . ~
REDUCTION OF THE TASTE ASSOCIATED
WITH
_ ;
SPECIFIC MATERIAL XCl SUCROSE CAFFEINE
. .
YES NO NO
I - . .
TAURINE YES NO NO l l ~
K-2,4-DHB YES NO NO l : - I
N-CN-$-ASP-PHE YES NO YES
N-NO2-$-ASP-PHE ~ ~ YES NO YES l I
LAC~ISOLE YES YES YES

N-CN-$-U-So3 NO YES YES
_ ~here: ~
L-aspartyl-L-phenylalanine potassium 2,4-dihydroxybenzoate ;~ N-(p-cya~nophenylcarbamoyl)-L-aspartyl-L-phenylalanine N-tp-nitrophenylcarbamoyl)-L-aspartyl-L-phenylalanine 2-~4-methoxyphenoxy)propionic acid N-(p-cyanophenylcarbamoyl)-aminomethanesulfonic acid.
It will be clear to anyone skilled in the art that the above table is not alI inclusive as to tastands and/or tastes.
As used herein and in the appended claims, a "taste"
~; shall mean any taste which is salty, bitter, sweet, sour, alkaline, uma~i,;astringent, tangy, dry, sharp, cool, hot, burning, acidic, spicy~ pungent and/or metallic. Such taste shall include any and all taste(s) as well as any and all aftertaste~s). Once again this list is not all inclusive as one skilled in the art would recognize.
As used herein an "eatable(s)" shall mean any material ingested. Eatables shall include, but not be limited, to materials ingested by humans, other mammals, fish, birds, ' `CA21 ~ ~28~
W O 93/10677 PC~r/US92/10179 and other an.i~mals.
By the term "substantially tasteless" as used herein and the appended claims is meant a compound that has substantially no taste upon initial ingestion at the levels that are appropriate to be a tastand. qShe aftertaste, if any, is not included in this definition.
By the term "~weetener" as used herein and the appended claims is meant any material which gives a sweet perception, including but not limited to:
~: A. monosaccharides, including but not limited to aldoses and ketoses beginning with trioses, including but not limited to glucose, galactose, and fructose, B. compounds gene~~cally known as sugars, which include but are not limited to mono-, di- and oligosaccharides including but not limited to sucrose, maltose, lactose, etc, : C. sugar alcohols which include but are not limited to :~: sorbitol, mannitol, glycerol, D. carbohydrates and polysaccharides whic~ inc}ude but are not limited to polydextrose and maltodex~-in, E. high intensity sweeteners.
As used herein and the appended claims "high intensity sweeteners" shall include but are not limited to:
L-aspartyl-L-phenylalanine methyl ester (As~artame~3 and other related dipeptide sweeteners, saccharin, L-aspartyl-D-alanine-N-(2,2,4,4-tetramethyl thiatan-3-yl)amide (Alita~e^), 1,6-dichloro-1,6-dideo~y-~-D-; fructofuranoysl-4-chloro-4-deoxy-~-D-galactopyranoside (Sucralose ), 6-methyl-1,2,3-oxathiazin-4(3H~-one 2,2-dioxide (Acesulfame ~, 6-methyl-1,2,3-oxathiazin-4(3H)-one 2,2-dioxide potassium salt (Acesulfame-K~), cyclohexylsulfamic acid ~Cycl~mate ), N-(L-aspartyl)-N ~2,2,5,5,tetramethylcycl~pentanoyl)1,1-diaminoethane ~:~ and its related compounds, guanidinium class sweeteners, dihydrochalcone class sweeteners, stevioside, miraculin and thaumatin, and their phys~ological~y acceptable salts. Many more sweeteners are described in the following publications, which are : hereby incorpor~ted by reference:

Wo93/10677 C A 2 1 1 7 2 84 7 PCr/US92J10179 1. Walkers, D.E., Orthoefer, F.T!, and DuBois, G.E. J (Ed.), "Sweeteners Discovery, and Molecular D~cign, and Chemoreception," ACS Sy~posium Series 450, American Chemical Society, Washington, DC~
1991, and 2. Grenby~ T.H., "Progress in Sweeteners,"
Elsevier Applied Science Series, Elsevier Science Publishing, L~ndon and New York, l9B9.
The authors racognize that this list, or any zther list, is not and cannot be all inclusive.
By the term "low intensity sweet~ner" as used herein and the appended claims is meant.any sweetener ~xcept a high intensity sweeteners.
By *he term "masker" as used herein and the appended claims is m~an~ any flavorful eatable which is u~ed to cover and/or dis~ui~e and/or obscure an undesirable taste.
Two examples ~f .atables which are commonly used as ma~kers are ~w~teners and spices such as onion, garli , paprika, r~d pepp~r, chili powderS etc.
By the term "low calorie eatable" or "low caloxie formulationl' as used he~ein and the appended claims i~
meant any eatabl~ in which the eatable has been ~urposely formulated for the reduced caloriP market. Typically ~hi~
has resulted in greater than twenty-five percent ~>25~) of th~ calori~s having been removed from said eatable that would~have been present in the r~gular non-low calorie :formulation.
The ter~ "tastand" as used herein and the appended claims means an eatable, except for:
1. he class of compounds s~own in the following W(~93/10677 GA2~ ~ 7~ PCr/U~92/10179 . 8 figure:
,, , ,, X ~ C-- --C H 2--5 0 3 H

W h e r e i n X r e p r e s e n t s H C H 0 , CN, C02Cl-C3al3cyl, COCl-C3alkyl, CO~H2 Br, Cl, F, I . or N02 or physiologically acceptable salts thereof .
, , ~
and then as appl ied only to the c:ase of organic:
bitter, axld, 2 . L-glutamyl~L glutamic acid ( or ~;alt thereof ) which when mixed with or when ingested along with another eatable saia~ eatable ha~ring an undesirable taste(s), will eliminat~ or sub tantially reduce said und~sirable taste (s) wil:hout introducing a taæl:e of its own at ~aid level of usage .
Tastands can also be salt ta~tands ., Tastands . lave the propert:y that they will block one unde~irable taste for exa~nple, bitter,: and/or in some ca~e~ at the saJne ime anoth~r undesirable t~ste. A speciiEic tastand may have its own particular ~aste but its ability to block an undesirable tast~ occur~ at a concentration belc~w that at which ilts own par~icular taste is p@rceptibl~ Ta~tandæ may uncover tast~s and~or off-taste~ that w~re present in the ealt~ble before ~e addition of the tastand. A tastand will not in~roduce a~y ~ubstantial tas1:e and/or of ~-taste of its own. This property differerltiates tastands from masking materials. For example to determine if a tastand is a bitter blocker it could be added to a solution of a bitter mak~rial such as KCl. If the material is a tastand it will block or substantially reduce the undesiæabl~ taste of KCl before it imparts any significant taste of its o~,m. It is understood that a tastand may have th~3 ability to blo ::k one undesirable taste more effectively than another undesirable taste. Some tastands may block on y one undesirable taste W093~10677 C A 2 1 1 7 2 ~ 4 PCT/US92/10179 effectively. A given tastand may, for example, blo~k the perception of bitter at a level of 10-20 ppm but require lO00-lO,000 ppm in order to effectively block another undesirable taste and/or tastes or it may not block the perception of another undesirable taste or tastes at any concentration. This relative effectiveness or inability to block certain tastes at all will vary from tastand-to tastand and/or with concentration of ths same tastand. Some specific tastands may block tastes that are not undesirable in certain specific applications such as sweet. Some tastands when added to an eatable may increase the perception of another taste for example the level of saltiness of the eatable. The blocking of an undesirable taste may allow in some cases an increased sensation of another taste. In this particular instance the increased salt sensation that is perceived by the addition of a tastand is allowing the tastand to act as if it were a salt enhancer.
A "salt tastand~ as used h~rein and in the appended claims means a tastand which, is itself salty or is combined with another salty eatable, and when mixed with or when ingested along with an eatable possessing an undesirable r.aste will reduce or eliminate the perceived undesirable taste(sj of saî-d ea~able. Examples of such salty eatables that could be used with a tastand to make a salt tastand would be NaCl, KCl, or NH4Cl.
As used herein and the appended claim~ many of the tastands and ~atables are molecules ~amed ~ariously as alts and/or acids. It is obvious to one skilled in the art that these terms are arbitrary and virtually any acid can be a salt and vice versa depending upon the macroenvironment and/or microenvironment that the molecule is in. This environment can, in some instances, change the efficacy of a particular tastand. For example, 2,4-dihydroxyben~oic acid is not nearly as potent a tastand of the off-taste of KCl as is potassium 2,4-dihydroxybenzoate.
(In some specific acid environments the potassium 2,4-dihydroxybenzoate may lose some of its effectiveness.) Consequently, throughout the body of this patent and the W0 93/10677 C A ~ PCT/US92/10179 appended claims, it should be understood the recitation of acid and/or base refers also to the physiologically acceptable salts and the recitation of a salt refers to its corresponding acid and/or base.
The solubility of the tastand in water may not be suf f icient to demonstrate the blocking ability. In this case the tastand's solubility could be increased-by the use of other substances to help this lack of solubility. Ethyl alcohol is one example of a material which can be used to increase the solubility of potential tastands to be used in the above referenced tastand test.
Surfactants can affect the tastand by either increasing or decreasing the effectiveness of the tastand.
As used herein and~in the appended claims, a "surfactant"
shall mean an amphi ~ic molecule. Such surface acti e agents shall includ- lt not be l mited to soaps, and/_r detergents, whether ~.nic or non-ionic, and/or ~.mbrane lipids. Some surfactants can increase the effectivenes~ of ome tas~ands while the same surfactant may lessen the effectiveness of other tastands or not affect that particular tastand at all. Surfactants may affect each tastand differently. The surfactant that affects one particular ta~tand;in~a positive, negative or neutral æense may affect another~tastand differently (i.e. a positive, negative or neutral sense and not necessarily in the same way).
Different transformations, as such term is used ~ ~ .
hereinbelow,~ of a material may al~o have a profound effect on its tastand~char w ter.
Many of the above tastand principles can be demonstrated with potassium 2,4-dihi~roxybenzoate (potassium ~-resorcylate). This material in about one to two percent (1-2~)~w/v solution is sweet. When potassium ,~
2,4-dihydroxybenzoate is combined with KCl at, for example, 0.25% to 0.50% by weight relative to the KCl (depending upon the individual's sensitivity to bitter) it will virtually eliminate the bitterness associated with the potassium chloride. (This means that in an eatable containing one percent (1~) KCl the amount of potassium ~:

W093/10677 C A 2 1 1 7 2 8 4 PCT/US92/~0179 11 "~c~
2,4-dihydroxybenzoate that would be needed would be only 2S
to 50 ppm.) Potassium 2,4-dihydroxybenzoate is also a tastand for the metallic taste associated with saccharin.
If 25 to 5Q milIigrams of potassium 2,4-dihydroxybenzoate is added to a can of soda sweetened with saccharin (69 to 138 ppm of potassium 2,4-dihydroxybenzoate relative to the soda) the metallic taste is substantially reduced or eliminated allowing other flavors in the soda to come through. In the above examples (25-138 ppm) potassium 2,4-dihydroxybenzoate is a tastand because of its ability to block bitter taste at concentrations where it by itself is substantially tasteless. Potassium 2,4-dihydroxybenzoate is sweet only at significantly higher concentrations. In contrast, sucrose is not a tastand in that a 2~ solution is sweet but even at this level the bitterness of KCl is not substantially diminished. Sucrose would be a masking material under~the current definitions.
The use of additives to debitter eatables has been attempted by others. Recently, a fairly comprehensive approach to this goal was reported in "Practical Debittering Using Model Peptides and Related Compounds" by Tamura M, Mori;N, Miyoshi T, Koyama, et al in Agric. Biol.
Chem. 54, (1)~41-51 (1990). The authors examined the following classes of compounds and strategies to debitter solutions of amino acids, amino acyl sugars and peptides:
A. Chemical modification.
B. Masking~agents~ such as cyclodextrins and starch.
C. Proteins and peptides such as skim milk, soybean casein, whey protein concentrate or casein hydrolysates. ~
D. Fatty sùbstances.
E. Acidic amino acids.
Chemical modification of bitter tasting materials led to , reduced bitterness but the materials were not tastands because the chemical modifications generally led to derivatives with~their own characteristic undesirable taste. Case studies 2-4 were based on a strategy of the direct interaction of the additive with the undesirable taste component of an eatable in order to prevent said CA2 1 1 728~
W093/10677 PCT/US92/tO179 undesirable taste component from reaching the bitter taste receptor. In case study 5, the authors used molar equivalents of "acidic amino acids" or taurine (the authors state that, "taurine, of course, is not an acidic amino acid although it has a sulfonyl group and shifts to the acidic region") to reduce bitterness.
The paper reports that under the conditions tested, the acidic amino acids removed some of the bitter taste but conferred their own sour taste to the test solution.
Taurine, according to figures 4 and 5 of the paper was ineffective at debittering solutions of Arg, Phe, methyl,2,3-di-0-(l-phenylalanyl)-~-D-glycopyranoside, Phe-Phe, or Arg-Pro-Phe-Phe at from 0.33 to 1.5 molar equivalents. The results from figures 4 and 5 are internally inconsistent with respect to valine tested in a solution at the 300 mM level. While figure 4 shows a less than fifty percent (<.SO%) reduction of bitterness when :
O.333 equivalents of taurine was added to the test solution, figure 5 shows >60% reduction when 0.22 equivalents of taurine`(67 mM) was added to the solution.
The inconsistent result of the taste tests indicate that Tamura did not contemplate an important teaching of the present invention~and~led us to repeat the taste test. It is also clear that~Tamura did not understand or contemplate the effect that a tastand can have on a taste test. This application teaches this effect hereinbelow.
As stated~above, we have repeated the taste test for valine. This was~dnne in a 300 mM solution of valine ~; ~
(conditions of~Tamura et al.) at various levels of taurine reported in the Ta w ra paper. The results we obtained were confirmed by an independent testing laboratory. The independent test laboratory's re~ults are summarized in the .

~ . ~

WO93/10677 CA21 172~4 PCT/US92/10~79 following table:
CONCENTRATIC~t OF TAURINE lIEAN VALUE OF THE BITTERNESS OF A

3 OO m~I SOLUTION OF VA~INE
___ . _ . _ _ _. _ CONTROL (O TAURINE) 9.6 66 ~M 9.5 -_ . _ 200 mM 13.3 3~0 mM ~ 11.4 I _ . ~
he data show that taurlne has virtually no effect on the bittern~ss of valine. When the tasting was repeated with taurine on an equal molar basis with the valine (three times the amount shown in Figure 4 of Tamura and sixteen times that amount shown in Figure 5), there was still >~0%
of the bitterness remaining in the valine test solution. We did not repeat the aspartic acid and glutamic acid taste tests as they, under the conditions of Tamura, et al., are not tastands. EYen at 300 mM level the paper shows that taurine was ineffective at "masking of the bitterness" of almost all solutions tested. The high concentrations uced in these investigations~ suggest that the authors intended to mask the bitter taste. The authors did not understand or even contemplate the concept of tastands.
The underlying assumption of any experiment that has a con~rol built into the methodology, is that the controls are accurate and repeatable. If blockers are used randomly, the controls are neither accurate nor repeatable. If a so called control is ingested followed by a food with a blocker, the subsequent tasting of the previously ingested control will be different. If the authors of the Tamura study had realized this they probably could have designed the protocols to avoid these problems and the reported results would have been accurate and repeatable.
In contrast to the above it is the teaching of the present application that a tastand, as defined hereinabove, can prevent bitter components from interacting with the taste receptor at concentratio~s where the tastand is tasteless or substantially tasteless. Prevention is by a WOg3~10677 C A 2 1 1 7 2 8 4 PrT/~S92/10179 direct interaction with the receptor site, as such term is used herein, to prevent or substantially eliminate:
A. the interaction of the undesirable tasting molecule(s) with the taste receptor and/or B. the recognition of the undesirable taste.
Glenn Roy, Chris Culberson, George Muller and Srinivasan Nagarjan in US patent number 4,944,990 dated February 19, 1991, described the use of N-(sulfomethyl)-N'-arylureas to inhibit or suppress sweet taste and organic bitter when mixed with sweet and/or organic bitter. ~The authors specifically state that their material does not affect the off-taste of inorganic bitter.) The example that these authors used to show that there was a perceived bitterness reduction was a 0.11% (1.1 mg/mL) caffeine solution to which 4 mg/mL of N-~sulfomethyl)-N -arylurea was added. Even while adding a four hundred percent (400%) excess of the bitter reducing ~aterial compared to the bitter eatable, the Roy et al resulted in only fifty percent (50%) reduction of perceived bitterness.
We ha~e demonstrated that low concentrations (0.05~) of potassium 2,4-dihydroxybenzoate can eliminate the bitter aftertaste o~ KCl and the bitter aftertaste of saccharin.
Only at much higher concentrations is potassium 2,4-dihydroxybenzoate sweet tasting. Similarly, according to our thesis, taurine should be a tastand and we have found, in contrast to the teaching of Tamura, et al., that taurine at five percant (5%j (3% on a ~olar basis) relative to KCl will eli~:nate or substantially reduce the off-taste of KCl. This ~ould mean that in a one percent ~1%) solution of , KCl (10 mg/mL~ only 0.5 mg/mL of taurine would be needed and if the blocker were potassium 2,4-dihydroxybenzo~te only 0.05 mg/mL of blocker would be need~d.
Similarly if ten ~10) mg of taurine is added to a can of soda (354 mL of soda per can; 28 ppm taurine) sweetened only with saccharin the off-taste of the saccharin is substantially reduced or eliminated, while the sweet taste is relatively unaltered.
The present teaching is analogous to a competitive inhibition with a hinding site of the receptor~s) and/or a w093/10677 C A 2 1 1 7 2 ~ 4 PCT/US92/10179 non-competitive inhibition with the site(s) that influences the receptor. As such, one of our teachings is that the tastand can be effective at a low tastand concentration when compare~ to the eatable with the undesir~ble tasté.
This distinction is not a minor teaching as in practical terms it would be impossible to add more of the debittering material tha~ the bitter materials. If the Tamura paper's lower level of proposed use for taurine (O.5 equivalents of taurine) is added to a one percent (l~) KCl solution, the resultant solution has a pronounced off-taste which was not present when only O~03 equivalents ~O.5% by weight relative to the KCl) was used. (If even the lowest level of taurine which was proposed in the Tamura paper is added to water, the water has an off-taste.) The off-taste of the taurine when added to the KCl solution is even more pronounced at the l.0 and l.5 equivalent levels reported in the paper.
~aurine is not a tastand at the usage l~vels proposed in t.le Tamura article. The Tamura article gives no indication that reducing the levels to l/5 to l/lOO of their proposed levels will gi~e better and more desirable taste test results.
According to the authors of the above referenced Tamura article the "debittering of peptides did not seem to work." The authors there concluded "However, even 1.5 equivalent of acidic amino acids did not work. Probably, we have to discuss elsewhere the order of attachment of taste functional groups to taste recaptors sites."
The teachings in this appli~ation alearly ~how that the debittering of peptides does work. If five (5) to seven and one half (7~) mg of L-aspartyl-L-phenylalanine is added to a soda sweetened only with L-aspartyl-L-phenylalanine methyl ester ~Aspartame) (354 mL of soda per can (14 to 21 .
ppm)) the off-taste of the L-aspartyl-L-phenylalanine methyl ester (Aspartame) is reduced or substantially eliminated. The L-aspartyl-L-phenylalanine that is added as a tastand to the material sweetened with the L-aspartyl-L-phenylalanine methyl ester (Aspartame~) is in addition to the amount of L~aspartyl-L-phenylalanine that may or may not be present from the breakdown product of the L-W093/10677 ~ A 2 1 1 7 2 8 4 PCT/US92/10179 aspartyl-L-phenylalanine methyl ester (Aspartame ) or as a manufacturing impurity. The use of L-aspartyl-L-phenylalanine as a tastand is an unanticipated result that was not previously known or contemplated. In fact while L-aspartyl-L-phenylalanine is one of the breakdown products of L-aspartyl-L-phenylalanine methyl ester (Asparta~e ), the breakdown of the L-aspartyl-L-phenylalanine methyl ester (Aspartame ) has not been considered a desirable occurrence. Both the manufacturers and users of the L-aspartyl-L-phenylalanine methyl ester (Aspartame ) go to great lengths to prevent this degradation. They attempt to do this by adjusting the formulations of the products in which the material i8 used. In addition, in the case of the manufacturer the undesirable breakdown of the product can be slowed down by~selling the material in a dry state, as well as by the purifica~tion of the material. (When L-aspartyl-L-phenylalanine is present as a manufacturing impurity it is typically present in an amount less than one percent (<1%) ~of~the L-aspartyl-L-phenylalanine methyl ester.) The~above~example of the addition of five (5) to seven and one half~(7~) mg of L-aspartyl-L-phenylalanine would be about four percent (4%) of the L-aspartyl-L-. ~
phenylalanine methy;l ester that has been used to sweetenthe soda. Example~s~of the products that could be found from the~breakdown~o~the ~raspartyl-L-phenylalanine methyl ester in the~soda~ are~-L-aspartyl-~-phenylalanine, ~-L-;aspartyl-L-phenylalanine, methanol, L-aspartyl-L-phenylalanine~diketopiperazine, L-phenylalanine, L-aspartic acid, L-phenylalanine~methyl ester and ~-L-aspartyl-L-phenylalanine methyl ester. The ratio of these and other possible breakdown products will vary according to th~
conditions~of storage (time and temperature) as well as the soda's specific composition its pH, etc.) The present invention teaches~the use of the breakdown products, whether such;breakdown occurs deliberately or accidently, o~ the L-aspartyl-L-phenylalanine methyl ester (Aspartame~) into one or more tastand(s). Another example of a breakdown product of the L-aspartyl-L-phenylalanine methyl ester (Aspartame~) that is a tastand is ~-L-aspartyl-L-W093/10677 C A 2 1 1 7 2 ~ 4 PCT/US92/10179 17 ~
` 3 phenylalanine.
If the soda is sweetened with both L-aspartyl-L-phenylalanine methyl ester (Aspartame ) and saccharin then two tastands may be needed to reduce or substantially eliminate the off-taste of the two high intensity sweeteners. For example both taurine and ~-aspartyl-L-phenylalanine could be used. The levels of the tastands that would be needed would depend on the relative levels of the high intensity sweeteners that were used in the soda.
Combination of tastands are sometimes preferred. On potato chips, a salt consisting of a ratio of eighty percent (80%) KCl and twenty percent ~20%) NaCl with taurine at five percent (5%) relative to the KCl and three percent (3%) L-aspartyl-L-phenylalanine is sometimes preferred to a single tastand. Such single tastand could be for example taurine, L-aspartyl-L-phenylalanine or potassium 2,4-dihydroxybenzoate.
The results of our tastings have confirmed that any methodology that employs a random presentation of eatables both with and without blockers is flawed because the random presentation of eatables with and without blockers causes the "controls" to move. The taste evaluation of the controls will be altered by the use of the blockers in the same randomized tasting. This "moving" of the controls will occur because~the blockers are consumed before the eatables that do not contain the blocker~. (If an eatable that was found to be bitter~in a previously conducted taste test were presented~to the panelist at or near the end of the tasting that contained a tastand, the typical result would be that the previous~ly bitter food is no longer nearly as bitter.) In~ome;tests conducted in a randomized manner, pure KCl foods,~for exampIe, which were earlier determined to be very bad,~ bitter and metallic, during the first round of testing, were then determined to be almost as good tasting as NaCl fo ds when tasted at or near the end of the tasting.
The qualities of tastands described throughout this document are in sharp contrast to those of gymnemic acid as reported in The Merck ndex (Eleventh Edition, 1989) WO93f10677 C~ 2 1 1 ~ 2 ;~ ~ PCT/US92/10179 (hereinafter "Index") where it is stated that gymnemic acid ~Completely obtunds taste for several hours for bitter or sweet, ..." (This description of the properties of gy~nemic acid is not entirely consistent with the articles that were quoted for this information in the Index, one of which states, "After chewing one or two leaves one is unable to detect the sweet taste, and the bitter taste is also suppressed to some extent.") (emphasis added) The Index also states that gymnemic acid is a bitter tasting compound. More recent publications that have used purified gymnemic acid A1 and A2 have shown that there is a profsund effect on the sweet response that is still present after more than fi~teen minutes. These reports state that there is no effect on the bitter response. The reports do not comment on the taste of gymnemic acid A1 and A2~
nevertheless gymnemic acid is not a tastand under the definition contained herèin.
~ ~, An abundance of literature exists on the study of the perception of taste, particularly in the area of sweet taste. Over the past two decades, numerous researchers have attempted to deyelop new non-caloric sweeteners. This work began in earnest following the introduction of Aspartame (L-aspartyl-L-phenylalanine methyl ester) several years ago. As a result of this work, a large variety of sweet molecules are now known.
There has been a substantial amount of work on the perception of ~sweet~taste, as well as on the interaction of lecules with~;the receptor for sweet taste. All of this work points to the fact that the sweet receptor and the bitter receptor as well as the other taste receptors may be in close proximity andJor related to one another and/or possibly one~and the same. It is now known, for example, that if sweet molecules are altered slightly, particularly in their spatial arrangements and/or orien~ation and~or configuration of their chiral centers and/or their stereochemistry and/or by the addition or substitution and/or elimination~in the molecule of various groups, that such molecules may become bitter or tasteless. Throughout this document the alteration of a molecule in its spatial WO93/10677 CA2t 1 7284 PCT/US92/1~179 19 "
arrangements and/or orientation and/or configuration of its chiral centers and/or its stereochemistry and/or by the addition or substitu~ion and/or elimination in the molecule of various groups, will hereinafter be referred to as "transformation(s) Il. Sometimes the transformation of a molecule that:
A. is a tastand will change said molecule in~o a molecul~ that is a more active tastand or less active tastand or not a tastand at all, or B. is not a tastand will change it to a tastand.
Such transformations in a molecule may change the mol~cule from any one of these (sweet, bitter ox tasteless) to any : of the following: sweet, bitter or tasteless.
Consequently, it occurred to us that:
A. the perception of sweet and the perception of bitter may be associated with the same receptor, part of the same~receptor, very closely spatially related receptors or separate receptors which act together tG
give the associated sweet or bitter taste response, and B. that the:perception of undesirable tastes ~ay be associated~with this sams r ceptor, part of this same receptor or very closely spatially related receptors ~: or separate~receptors which act together to gi~e the :~ aæsociated undesirable taste.
::
(all concepts relating to the receptor~s) are herein referred to~as "reoeptor site(s)" or ~receptor(s~U).
This transformation feature is well illustrated in the case of the:dipeptide-like sweeteners. For instance, L-:~ aspartyl-L-phenylalanine methyl ester (Aspartame~) is : inten~ely sweet. Whereas, L-aspartyl-L-phenylalanine .
:

WO93/10677 CA 21 1 7284 PCT/USg2/10179 methylamide is intensely bit~er and L-aspart~l-L-phenylalanine free acid is ~astele,s.
_, ,, , . . ~

~ ' ~ ' L-AS-L-PHE METHYL ESTER L-ASP~L-PHE METH~L AMIDE
ASPARTAME SlIEET E~ITTER

L- ASP- L- PHE
TASTELESS

Th-.se transformations extend to almost all of the known dipeptide classes of sweeteners, including the aspartyl-~-alanine amides where many of the aspartyl-D-alanine alkylamides ~re sweet and many of the coxresponding L-amides are bitter. A similar set o~ examples exist for the mino malonic acid derivatives, the aspartyl alanine esters and most other cla~ses of peptide-like ~weetener compounds.
.
Trans~ormations also extend to many other classes of compounds. For example, in the saccharin type molecules the presence or a~sence of nitration or alkylation can lead to a molecule that is tasteless or sweet or bitter. This is CA21 1 728~
WO 93/10677 PCI`/VS92/10179 21 "
illustrated in the following examp~ e:
o o ~C\ a ~C\ .

S~rE E T ~ E R

¦ ~ ~N N - C H

Another~example of a transformation can be seen in the substituted propoxybenzenes where the position, the locat.ion ~nd the m~mber of the NH2 and the N02 substituents determine if the molecule is tasteless or sweet andJor bitter~ This is illus~.rated in the following example:
OCH21 H2C~ OCHaCH
2 ~2 No2 ~a :: : ~ I ^

~: ~ASTELESS
~: ~ :
Another example of a transformatiorl can be seerl in the ;~:

~; ~
.

WO 93/10677 i C A 2 1 1 7 2 8 4 Pcr/VS92/10179 . 22 substitllted ethoxybenzenes.

IlH-c-l~H2 ~ ~1U-C-NH2 S~ E~ ~ a I TTER .

Another example of a transformation can be seen in the following:
. _ ~ _ rut Ino~- ~3 H

l~tT~ER OH O 14A~IIICIN

: 011 ' ,-~ }C~I

~AStElESS OH HESPEI~ I D I ~I
' Such transformations can be extended to most classes of swe~t or bitter tasting substances. Consequently it is likely that a non-sweet analogue of thaumatin ~a large peptide) exi~ts which would be a ta~tarld. In general most sweet or bitt-r eata~le ~hould be able to be transformed into a tastand regardless of the ~ize or chemical struc~ureO Irl additionO polymeric substances, as well as di-, oligo-, and poly-peptide substances would also he anticipated by the present di~closure.
These facts lead us to the conclusion:
Pl,. 1. if a molec:ule pO55 ssed simiiar spatial arr~ngeraents to known sweeteners; and 2. with slight alt~rations the molecule could be made substantially tasteless 23 ~`
B. l. if a molecule possessed similar spatial arrangements to a known bitter substance; and 2. with slight alterations the molecule could be made substantially tasteless that such molecules should interact with the receptor in the same way a sweet or bitter tasting molecule would interact but without the associated taste. If this occurs, then this substantially ta~teless molecule ~hould inhibit the entrance of other molecules into the receptor.
Consequentlyr we concluded and discovered the following:
A. If the molecule is a tastand, it may inhibit or reduce the sweetness of substances, and in some instances it will also inhibit or reduce undesirable tastes; and/or B. If the molecule is a tastand, it may inhibit or reduce the bitterness of substances, and in some instances it will also inhibit or reduce other undesirable tastes; and/or C. If a sweet molecule can be spatially altered to become substantially tasteless, this molecule will likely be a tastand; and/or D. If a bitter molecule can be spatially altered to become substantially tasteless, this molecu~e will likely be a tastand.
In addition, it has been found that when an eatable possesses desirable characteristics, for exa~ple, a salty taste, these desirable characteristics may not be inhibited or adversely a~fected by the tastand inhibitors of the invention.
In addition, in order to achieve a desired degree of reduction and/or elimination of undesirable taste(s), it has been found that more than one tastand might be needed in some cases. If more than one tastand is necessary, then it would be obvious to one skilled in the art to either have each one of the tastands ingested in a temporally appropriate manner and/or to chemically link the tastands.
In the case of chemically linked tastands the basic molecule could be linked with one or more similar or dissimilar tastand molecule(s).
, WO93/10677 CA2~ 172B4 PCT/VS92/10179 In addition, synergism of molecules in some cases may allow two or more molecules, that in and of themselves do not appear to be tastands, to act as a tastand when said molecules are used in a temporally appropriate manner.
It has further been found that many of the tastands will block or inhibit the undesirable taste(s) of, to mention a few examples, potassium chloride, potassium glutamate, potassium benzoate, potassium nitrate, pota~sium nitrite, potassium sulfate, potassium sulfite, potassium baking powder and potassium baking ~oda (which probably become potassium chloride or other potassium salts after baking), aspirin, acetaminophen, antibiotics, codeine, caffeine, unsweetened chocolat~, other medicaments or other undesirable taste(s) of the eatable.
Some tastands h~ve also been found to enhance alt taste. Thus tastands can be used in conjunction with ~ixtures of æubstances with undesirable tastes such as, for example, potassium chloride and/or sodium chloride and/or aDonium chloride to both reduce the undesirable taste(s) and to enhance the salt taste of the sodium and/or potassium and/or ammonium chloride.
Eatables which are not generally considered to have an undesirable taste cou1d also benefit from the addition of an appropriate tastand as a taste modifier. For example:
A. Sodium chloride, which is normally not considered bitter, is substantially smoothed in its aftertaste ~ ~ with the addition of the appropriate tastand.
; ~ B. A smoothing effect can be achieved when a ta~tand is added to plain unflavor~d, unsweetened yogurt which is normally considered tangy or acidic tasting.
C. The bitter taste of coffee can be substantially reduced or eliminated with the addition of the appropriate tastand.
D. The burning sensation of hard liquors can be reduced or eliminated with the addition of the appropriate tastand.
In the case of sour materials such as lemon juice when the appropriate tastand and/or salt tastand is added there is a substantial change in the undesirable taste. This is .

WOg3/10677 CA~ 17~4 PCT/U~92/10179 especially true if a salt, such as potassium or sodium chloride, is added to the tastand. If a salt tastand is added, the undesirable taste can be reduced or even eliminated.
As used herein a~d the appended cl~ims the singular and the plural of a defined term shall be one and the same.
As used ~erein and the appended claims defined terms with :~
a~d without initial capitalization shall mean one and the same.
':
DETAILED DESCRIPTION OF THE INVENTION
Tastands Molecules as Taste Modifiers -~ The tastands useful in the present invention are those compounds of the prior art which are tastand s that are substantially tasteless. In many instances, substances of th~ prior art which could be tastands which are not :
tasteless can be rendered substantially tasteless by transformation(s).
~: As used herein~and the appended claims, "Group l"
~:: substituents may be represented by:
H, alkyl, substituted alkyl, a}koxy, s~bstituted alkoxy, aryl, substituted aryl, alkylene, substituted alkylane, amînoacyl, substituted aminoacyl, aryloxy, ~:.
substituted aryloxy, hydroxy, nitro, amino, substituted amino, cyano, halogen, aralkoxy, substituted:araIkoxy, acyl, substituted acyl, aryl~yl, substituted arylacyl, trifluoroacetyl, benzoyl, substituted benzoyl, alkylamino, substituted alkylamino,~dialkylamino, substituted dialkylamino, trialkyla~ino, substituted trialkylamino, carbonates, substituted carbonat~s, alkylcarbonate~, substituted alkylcarbonates, arylcarbonates, substituted arylcarbonates, acylamino, substituted acylaminQ, guanidino, substituted guanidino, alkylguanidino, substituted alkylguanidino, acylguanidino, substituted acylgua~idino, arylguanidino, substituted arylguanidino, alkyurethanes, substituted alkyurethanes, arylurethanes, substituted WO93/10~77 CA ~ 1 ~ 7~;8~ PCr/US92/10179 ` 26 arylurethanes, ureas, substituted ureas, mono- or di-or tri- substituted ureas, alkylureas, substituted alkylureas, an O, S or N glycoside, or a phosphorylated glycoside ~where the glycoside is a monosaccharide, a disaccharide, a trisaccharide, an oligosaccharide, a ~ubstituted mono-, di-, tri-, or oligosaccharide3, CHO, substituted C~O, COCH3, substituted COCH3, CH2CHO, substituted CH2CHO, COOH, CH2COOH, substituked CH2COOH, COOCH3, ~ubstituted COOCH3, OCOCH3, substituted OCOCH3, CONHz, substituted CONH2, NHCHO, substituted NHCHO, SCH3, substituted SCX3, SCH2CH3, substituted SCH2CH3, CH2SCH3, substituted CH2SCH3, SO3H, S02NH~, substitutéd 502NH2, ~02CH3, substituted SO2CH3, CH2SO3H, substituted CH2SO3H, cycloalkyl, substituted cycloalkyl, heterocyclic, substituted heterocyclic, polycyclic; s~bstituted polycyclic,and CH2SO~NHz, arylureas, substituted arylureas, D ltiple substit~ted arylureas, an acid group o~. the structure Z~r ~herein Z i.-, an element sel~cted from the group consisting of carbon, sulfur~
boron or p~o~phorus, q is an int~ger from 2 to 3 and r i~ an integer from 1 to 3; carboxylic acid ester, ubstituted carboxylic acid ester, carboxamide, : ~ substituted carboxamids, N-alkyl carboxamide, substitu~ed M-a~lkyl carboxamide, di-alk~
carboxamides, ~ubstituted di-alkyl carboxamides~
: and~or two ub~tituents together represent an aliphatic chain linked to a phenyl ring at two positions, eith~r directly or via a an oxygenl nitrogen or sul~ur group, any H on N, S, or O, may be substituted with one of the substituents of Group 2, :and combinations of any and/or all of the foregoing, and physlologically acceptable salts of any and/or all of the ~oregoing.
: As used her in and the appended claims "Group 2~' s~b tituents may be represented by:
H, alkyl, substituted alkyl, dialkyl, substituted dialkyl, aralkyl, substituted aralkyl, aryl, substituted aryl, diaryl, substituted diaryl, acyl, 27 ~
~ ;~
sub~tituted acyl, cycloalkyl, substituted cycloalkyl, ~-~
benzoyl, substituted benzoyl, trifluoroacetyl, alkyloxycarbonyl, substituted alkyloxycarbonyl, :~
aryloxycarbonyl, substituted aryloxycarbonyl, :~
alkylaminocarbonyl, substituted alkylaminoca~bonyl, arylaminocarbonyl, substituted arylaminocarbonyl, ~i;
amidines, substitut~d amidines, alkylamidines~
substituted alkylamidines, arylamidines, substituted arylamidines, a monosaccharide, substituted a .
~onosaccharide, a disaccharide, substituted disaccharide, a trisaccharide, substituted trisaccharide, an oligosaccharide, substituted oligosaccharide, phosphorylated saccharides, substituted phosphorylated saccharides, arylacyl, substituted arylacyl, alkylene, substituted alkylene, heterocyclic, s~bstituted heterocyclic, polycyclic, substituted polycyclic, cyano, nitro, any H on N, S, .
or O, may be substituted with one of the above substituents, and combinations of any and/or all of the foregoing and physiologically acceptable salts of any and/or all of the foregoing. ~ ::
As used herein and the appended claims "Group 3"
~: substltuents may be~represented by::
~: H, alkyl, substituted alkyl, alkyIene, substituted : : alkylene, branched alkyl, substituted branched alkyl, branched alkyien~, substituted branched alk~lene, aryl, substituted a ~ l, aralkyl, ~ubstitut~d aralkyl, cycloalkyl,~substituted cycloalkyl, acyl, substituted `:
acyl, benzoyl,: substituted benzoyl~ alkoxy, substituted alkoxy, aryloxy, substituted aryloxy, trifluoromethyl, halogen, cyano, heterooyclic, substituted heterocyclic, poly~yclic, substituted p~lycyclic, and combinations of any and/or all of the foregoing.
As used herein and the appended claims 9'substituted"
indicates that the molecule may have any hydrogen atom replaced or "substituted" by any of the substituents of Groups 1, 2 c~ 3, in any combination.

WO93/10677 ~ A 2 1 1 7 2 8 4 PCT/US92/10179 As used herein and the appended claims specific tastands containing acidic or basic groups shall include all physiologically acceptable salts thereof as well as the free acid and/or base as is appropriate.
As use~ herein and the appended claims any aromatic mol~cule in Groups l, 2 or 3 above may be substituted with one of the substituents of Group l.
It would be understood by ~ne skilled in the art that any substituent not specifically defined is H.
It is understood by those skilled in the art that only the substitutions, replacements, and descriptions above, allowed by the laws of chemistry, physics and nature are contemplated for use as tastands as described in the classes of compounds below.
:: ~
Ill~strative of suitable classes of molecules contemplated for use as tastands are the following:
A. As used here~in and the appended claims the following molecule shall be referred to as A-l and said molecul.e represents the general class of compounds having the structure:~
:: : _ _ ':

A-l ~ L11 - 0~~

, -~

wherein m represents 0 or l, n represents 0, l, 2 or 3, p represents~l, 2, 3, 4 or 5, q represents 0 or l;
R represents H or a lower alkyl (e.g. of C1-C3 alkyl);
the substituents R', which may be the same or different, are each represented by one of the substituents of Group 1, in any combination. X~
represen's H or a physiologically acceptable cation, and physiologicàlly acceptable salts of any and~or all of the foregoing.
Some specific compo~nds within this class of tastands and their preparation are described in U.S. Patent No.

4,567,053 and are hereby incorporated by reference.
:

29 ..
Examples of compounds of particular interest wi~hin ;~
this class are:
~ 2-(4-methoxyphenoxy)propionic acid, 2. (+)-2-(4-methoxyphenoxy~propionic acid, 3. (~)-2-(4-methoxyphenoxy)propionic acid, 4~ 4-methoxypheno~yacetic acid,

5. 2-(4-methoxyphenyl)propionic acid,

6. 2-(4-ethoxyphenoxy)propionic acid,

7. 3-(3,4-dimethoxyphenoxy)propionic acid,

8. 3-~3,4-dimethoxyphenyl)propionic acid,

9. 3~2,3,4-trimethoxyphenoxy)propionic acid,

10~ 3-(2-methoxyphenyl)propionic acid,

11. 1,4-benzodioxan-6-acetic acid,

12. 3-(2,3,4-~rimethoxyphenyl)propionic acid,

13. 3-(3,4,5-trimethoxyphenyl)propionic acid,

14. 3~ methoxyphenyl)propionic acid,

15. 4-(4-methoxyphenyl)butyric acid,

16. 2-methoxyphenylacetic acid,

17. 3-methoxyphenylacetic acid,

18. 4-methylphenylace~ic acid,

19. 4-tri~luoromethylphenyla~etiG acid,

20. phenylpyruvic acid,

21. 2,3-dihydroxybenzoic acid,

22. 2-hydroxy-4-aminobenzoic acid,

23. 3-hydroxy-4-aminobenzoic acid, : 24. phenoxyacetic acid, 25. gallic acid, 26. 2,4-dihydroxybenzoic acid, 27. 2j4 dihydroxyphenyla etic acid, 28. 2-(2,4-dihydroxyph~nyl)propionic acid, 29. 2-(2,4-dihydroxyph no~y)propionic acid, 30. 2 (~,4-dihydroxyphenoxy)acetic acid, and the physiologically acceptable salts of any and/or all of the foregoing.
B. As used herein and the appended claims the following molecule shall be referred to as B-1 and said molecule represents the general class of compounds having W093/10~77 ~ A 2 1 1 7 2 8 ~ PCT/US92/10179 the structure:

~~C~O O :~

wherein R7 may be ~elected from the 3roup consisting of hydrogen and C~-~ alkyl, R~ may be selected from : the group consi ting of hydrogen and Cl-C3 alkyl and wherein R1, is the group, (as used herein and the appended claims the structure shall be referred to as B 2):

wher~in R2, R3? R4, R~ and R6 are independently elected from the ~ubstituenks of Group 1, in any combination, --and physiologically acceptable salts of any and/or all of the for~goin~
~ Some specific compounds within t~is clas~ of tastands :`~ are:describ~d in U~S. Patent No. 4,544,56S and are hereby incorpor~ted by ~reference.
~:~ Illustrativ:~member of particular interest in this clas~ include: ~ :
: l. 3-(3'-4'dimethylbenzoyl)prop~onic acid, :;
. 3-(2',4'-dimethylbenzoyl)propionic acid, 3. 3-~2'-methyl-4'-ethylbenzoyl)propionic acid, 4. 3-(2',4',6~'-trimethylbenzoyl)propionic acid, ~-5. 3~ carboxybenzoyl)propionic acid, 6. 3-(4'-hydroxybenzoyl)propionic acid, 7. 3-(3'-methyl-4'-hydroxybenzoyl)propionic acid, 8. 3-(2',4'-dihydroxybenozoyl)propionic acid, 9. 3-(2,4'-dihydroxy-6'-methylbenzoyl)propionic acid, 10. 3-(3'-methyl-4'-ethoxybenzoyl)propionic acid, ' WO93/10677 C~ 2 ~ 4 PCT/US92/10179 3l 11. 3-(3'-ethyl 4'-eth~xybenzoyl)propionic acid, 12. 3-(4'-methoxybenzoyl)propionic acid, l3. 3'-(4'-ethoxybenzoyl)propionic aeid, 1~. 3-(3',4'-dimethoxybenzoyl)propionic acid -`
15. 3-(4'-methoxybenzoyl)propionic acid 16. 3 t4'-methoxybenzoyl)-2-methylpropionic acid 17. 3-(4'-methoxybenzoyl)-3-methylpropionic acid, 18. 3',4'-dimethoxybenzoyl-2,3 dimethylpropionic acid, and physiologically acceptable salt~ of any and/or all of i-the foregoing. -~
C. As used herein and the appended claims the following molecule shall be referred to as C-l and said molecule represents the general class of compounds having the structure:

C~

wher~in R1, R2, R3, R~, Rs a~d R6 are i~dividually represented by one of the sub:stituents of Group 1, in any combination, and physiologica}ly accep~ed salts of any and/or all of the :fo~egoing.
~Some specific me~bers of this class of tastands are ::~partially described in U.S. Patent No. 4,871,570 and ~re hereby incorporated by reference.
Illustrative members of particular interest in this class include:
1~ R2=R3=R5eR6=H ~ R1=OC~H5, ~4=NH--2 1~ R1--OCHzCH2CH3 t R2=N02 r R4=NH2 ~ ~R3=Rs=R6=H
3. Rl=CH3, R2=NH2, R6-N02, R3=R4=R5=H, 4. R1-CH3, R2=N02, R4=NH2, R3=R5--R6--~H, : 5. 3,4-dihydroxybenzoic acid (protocateGhuic acid), 6. 2,4-dihydroxybenzoic acid~

Wo93/10677 CA 2 1 1 7 2 84 32 PCTlUS92/10179 7. 3-hydroxy-4-methoxybenzoic acid, . 3,5-dihydroxybenzoic acid, 9. 2,3-dihydroxybenzoic acid, 10. 2-hydroxy 4-aminobenzoic acid, 11. 3-hydroxy-4-aminobenzoic acid, 12. 2,4,6-trihydroxybenzoic acid, 13. 2,6-dihydroxybenzoic aci~
14. 2-amino tere-phthalic acid and physiologically acceptable salts of any and/or all of ~-~
the foregoing. ~ ~
D. As used herein and the appended clai~s the `.
following mo~ecu}e shall be referred to as D-l and said -.:
molecule represents the general class of compounds having , the structure~
. -_ .

D-l ¦ ( R ) p Y C ( C ~H 2 ) k C Y ( R ) q ( I ~ H 2 ) n -O~C ~ O - X ~ ' ' '"', '., wherein n and k independently may be 0, 1 or 2; Y ~`
(which may be~the same or different): may be N i;
(nitrogen)~ O:~oxyg~n), or S ~sulfur~; Q may be represented~:by one of the substituents of Group 3; p -.
and~q are~l:when;~ is O and p and q may be independently~l;;or 2 when Y is S and p and q may be independently~2 or 3 when Y is N; R (which may be the :~
same or dif~erent when p~l) and R' (which ~ay be the same or different;when q>l) are represented by one of the substituents of Group 2 or one of the following three structures (as used h rein and the appended claims the stxuctures shall be referred to as D 2) in ~-any com~ination and the appropriate stereochemi~try:

~.

:

W093/10677 CA2 117284 PCT~US92/10179 . . ~
7 ~ H o e c o z ~ c- z ~ N C
I 1.. ~ \..............
"~, COZ R R R
:-:~' wherein Z and Z' are the same or different and are represented by OH, -0~~, ORN, NH~, NHR~, N(R~)2,; R~

may be alkyI, branched alkyl, aryl, aralkyl, alkaryl, cycloalky~, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R~' may be alkyl, branched alkyl, aryl, .~

- aralkyl, alkaryl, cycloalkyl, substituted alkyl, ~

substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side ~: chain (e.g. one of the 20 common amino acids~, X~ may : be H~ or a physiologirally acceptable cation, preferably an alkali metal, alkaline earth metal or ~: a~monium cation, ~: and ph~sioloqically acceptable salts of any and/or all of the~for~going.~

IllustratiYe of compounds of particular interest in this class are~

L-aspartyl-L-phenylalanine, 2. aminomalonyl-L-phenylalanine, 3. L-aspartyl-D-alanine, 4. L-aspartyl-D-serine, 5. L-glutamyl-L-phenylalanine, ~6r N-(L-aspartyl;)-p-aminobenzoic acid, 7. N-(L-aspzrtyl)-o-aminobenzoic acid, : ~ 8. L-aspartyl;-L-tyrosine, 9. N-(p-cyanophenylcarbamoyl~-L-aspartyl-L-phenylalanine, lO. N-(p-nitrophenylcarbamoyl)-L-aspartyl-L

~ phenylal~nine, : ll. L-~-aspartyl-L-phenylalanine methyl ester, 12. L-aspartyl-p-hydroxyanilide, 13. L-~-aspartyl-L-phenylalanine :

l4. L-aspartyl-~L-serine methyl ester 1~. L-a~partyl-D-tyrosine methyl ester 16. L-aspartyl-L-threonine methyl est~r 17. L-a~partyl-L-aspartic acid and physiologically acceptable salts of any and/or all of the foregoing. ;
E. As used h~rein and the appended claims the ;
~ollowing molecule shall be referred ~o as E-l and said molecule represents the general class of compounds having -~
the structure:
. . . .
E-l \ N~
R - N - C - N ~ ~ Z

. .
wherein R , R~, R"', R6 are each independently represented by on~ of the substituents of Group 2, in ;~ any combination; R4's and R5's which may be the same or different are each independently represented by one .
of the substituents of Group 3; n may be 0, l, 2, 3, :
; ~ 4, 5, 6, 7, 8, 9~or lO; Z may be C, S, P or B, q is an :~. integer from 2 to 3 and r is an integer from l to 3, when Z is C, q is 2; when Z is S, P or B, q may be 2 ;~ or 3; when~Z is~C or S, r is l; when Z is P or B, r is : 2, and physio}ogically acceptable salts of any and/or all of ; the foregoing. :~
: Illustrative of: compounds of particular interest in this class are: .
l~ R~-CH3,~R~'-4-cyanophenyl, R =R4=R5=H, n=l, Z=C, q=2, r=l, : ~ 2. R"=CH3, R"'=4-nitrophenyl, R =R4=R5eH, n=l, Z=C, q=2, : 3. R"=CH3, R~'=4-methoxyphenyl, R =R4=R5-H, n=l, Z=C, , W09~/10~77 CA2~ 17284 PCT/V~92/lOi79 35 ,,~
~. RN=CH3, R"'=ph~nyl, R =R4-R5=H, n=l, Z=C, q=2, r=1, SO R"=H, R~'-4-cyanophenyl, R =R4=R5=H, n=1, Z=C, q-2, ~--1 , ,.
6. R~H, R~'=4-ni rophenyl, R =R4=R5--H, n-1, Z=C, ~=2, 7. Rn=H, R~'=4-m~thoxyphenyl, R =R4=R5=R, n-l, Z=C, q=2, ~`
r=1, ~. R~=H, R~' =ph~nyl, R aR4=R5=H, n=l, Z=C, q=2, r=1, -~
9~ R~CH3, R~'=4-cyanophenyl, R =R4=Rs~H, n=l, Z=S, q=3, r-l, 10. R~=CH3, R'N=4-nitrophenyl, R =R4=R5~H~ n=l, Z=S, q--3, r=l, -~
11. R"=CH3, R~-4-methoxyphenyl, R =R4=R5=H, n=1, Z=S, q=3, r=1, 12. ~"=C~3~ R"'=phenyl, R -R4=R5=H, n=l, Z~S, q=3, r=l, 13. R~/=H, R"'=4-cyanophenyl, R -R4-R5-H, n=l, Z-S, q=3, 14. R"=H, R~'=4-nitrophenyl, R =R4=R5--H, n=l, Z-S, q=3, r=l, , 15. R~=H, R~'=4-m~tho~yphenyl, R --~4=Rs=~, n-1, Z=S, `~
~--3, r=l, : ~ 16. R~=H, R~' =phenyl, R =R4- R5=H~ n=1, Z=S, q=3t r=l, and physiologically accep able salts of any and/or all of : the foregoing.
F. As used hex~in and the appended claims the follo~ing molecule shall be referred to as F 1 and said mole~ule rep~esents the general class of compounds ha~ing :~

~he structure:
~ , . . .
Q O
F~l I 1 1 , ( R ) p~ ( CP 2 ) n C ( ~ q .

wherein n may be 0, 1 or 2; Y (which may be the same or dif~erent) may be N (nitrogen), O (oxygen~, or S
(sulfur); Q may be represented by one of the substituents of Group 3: p and q are l when Y is O and p and q may be independently 1 or 2 when Y is S and p and q may be independently 2 or 3 when Y is N; R

: 36 :-. ;
(which may be the same or di~ rent when p>l) a~d ~' ~;
(which may be the same or d. rent when q~l) are represented by one of the s~_ ituents of &roup 2 or one of the ~ollowing three structures ~as used herein and the app~nded claims the structures ~hall be referred to as F-2) in any combination and the ~
appropr~ate stereochemistry: . -~ . .
I I R I I , --C--C O Z C C--Z --C--N--C
: COZ R' ' I'" R ' ~`

F-2 .
wherein Z and Z' are the same or different and are represented by OH, -O X~, ORN, NH2, NHR~, N(R")2,; R~ is alkyl, branched alkyl, a~yl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, ~ubstituted cycloalkyl sub~tituted aryl, substituted aralkyl, substituted alkaryl, and~R~ is alkyl, branchéd alkyl, aryl, aralk~l, alkaryl~,~ cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain te.g. one~of the 20 common amino acids). X~may be H~ or a::physio}ogically acceptable cation, preferably an~ alkali metal, alkaline earth metal or ammonium cation, ~
and physiologically acceptable salts of any and/or all of the foregoing.~
Illustrative of compounds of particular interest in this olass are:
l. L-methionyl-L-phenylalanine methyl ester, 2. L-leucyl-~-phenylalanine methyl ester, 3. L-seryl-L-phenylalanine methyl ester, 4. L-me~hionyl-D-alanyl-tetramethylcyclopentylamide, 5. L-seryl-D-alanyl-tetrame~hylcyclopentylamide, 6. L-leucyl-D-alanyl-tetramethylcyclopentylamide, 7. L-ornithyl-~-alanine 8. L-diaminobutyryl-~-alanine W093/10677 PCT/USg2/10179 C ~l 2 1 1 7 2 8 4 ~ ` ~
9. L-diaminopropionyl-~-alanine 10. L-lysyl-~-alanine and physiologically acceptable salts of any and/or all of ;~
the foregoing. ~-G. As used herein and the appended claims the -following moiecule shall be referred to as G-1 and said molecule represents the general class of compounds having ..
the structure:~

G~

. .
: .
~wherein p may:be 1, 2, 3, 4, or 5; the substituents may each be represented by one of the substituents of Group 1, in~any~co~bination, and R2 may be represented by one of the substituents of Group 2, and~physiolog~cally acceptable salts of any and/or all of i~
the foregoing.
: ~ -Illustrative of compounds of particular interest in `
this~class are:~compounds where R2=H and R1 is: !
1. 3-COOM,~
2. 3-COOCH
3. 3-COOC~Hs,::
4. 3-CH30,~
5. 4-CH30,~
6. 2-Cl, 7. 3-Cl, :
8. 4-Cl, ~
9. 4-CC~C~Hs, ..
10. 3-C6HsCH20~, 11. 4-C6HsCN20, 12. 2-t-butyl,:
13. 4-t-butyl, ~ :
14. 2-CH3, 15. 3-CH3, 16. 4-CH3, 17. 3-CZHs~
..

;,J 7 ~

1~. 4-~2H~, l9. 3,5-di CH3, and physiologically acceptable salts of any and/or ~ll of the foregoin~.
H. As used herein and the appended claims the ~ :
following molecule shall be referred to as H-l and said molecule represents the general class of compounds having `~
the structure: .
R~ ~:
: I ,~

:.
wherein R1 is 5-tetrazol, p may be l, 2, 3, or 4; and ~: the substituents: RZ, which may be the same or- ;
different, may~each be represented by one of the ; substituents of:~Group l~ in any combination; and R3 is : : represented by one:of the substituents of Group 2, and~ physiologically~acceptable salts of any and/or all of the foregoing.
Illustrative ~of compounds ~of parttcular interest in th:is class are ~
5-t~etrazolyl-6-chlorotrypta~ine, ; 2. 1-~-5-tetrazolyl-S-fluorotryptamine, 3. 1-a-~-tetrazolyl-6-methoxytrypta~ine, and physiolog:ically~acceptable salts of any and/or all of the foregoing.
- ~ I. As used~herein and the appehded claims the ~ : following molecule shall be referred to as I-l and said : ~
: ' ,,.
`:

W093/10677 CA21 17284 PCl`/US92/10179 3 9 ~ '.
molecule represents the general class of compounds having the structure:
.. . . r . . . . --C--C--C

( R 1~ ~ R 2 ~

wherein p and q may be independently lt 2, 3, 4, or 5;
and the ~ubstituent R1 and R2, which may be the same or dif f erent, each may be represented by one of the substituents of Group l, in any combination ~
and physiolos~ically acceptable salts of any and/or all of the f or~going .
An illu~trative of c:ompound of particular interest in this class is, which hereinafter shall be referred to as:
I-2 ~ 3~ c~CI1 ¦

J. As used herein and the appended claims the follcwing molec~le shall be referred to as J-l and said mol~cule repxesents the general class of compounds having the struc:~ure:
, .

: ~ , ~ '`5_o ~:
J-l ¦R2~ ~RI¦

,, wherein, R1 is repres~nted by one of the substitu~nts oP Group 2, and R2 and R3, which may be the same or different, may be represented by on~ of the substituents of Group 3, in any combination, and physiolo~ically acceptable salts of any and/or all oiE
the f oregoing .

Wo93/10677 C A 2 1 1 7 2 8 4 PCT/US92/10179 `; '' 40 "
Illustrative of compounds of particuiar interest i~ ~;
this class are: ~
1. R3=CH3, R2=H, ~1=isopropyl, ` :
2. R3=benzyl, R2=H, R~=H, :;`
3. R1=R3=H, R2=COOH, 4. R2=R3-H, R2=p-cyanophenylcarbamoyl and physiologically acceptable salts of any and/o~ all of the foregoing.
K. As used herein and the appended claims the following molecule shall be referred to as K-l and said molecule represents the general class of compounds having :~
the structure:

~-1 L~3 : :wherein p may be l, 2, 3 or 4; the substituents R2, which may be the: same or~different, are each ~ : represented by one of the substituents of Group l, in :: any combination,~and R1 is represented by one of the substituents of~Group 2, wherein R1 and R2 may be present, in;~any combination, and:physiologi~ y~acceptable salts of any and/or all of the foregoing.~
An illustratlve~of compound of particular interest in this class is~
l. R1=E, R2=benzyl:, p=l, ~:
~: 2. R1=H, R2=NOz:,~ p=1, ..
3. R1=H, R2=CN, p=l, ~`
4. R2=H, R1=cyanophenylcarbamoyl . -.
and physiologically~acceptable salts of any and/or all of the foregoing.:

:, CA2~ 1 72~3~
W~93/10677 PCT/U~92/10179 4 1 ~. r L. As used herein and the appended claims the following molecul~ shall be refexred to as L-l and said molecule represents the general class of compounds having the structure:
. . . . ~ ~

R
~ C R ~ p N 1 C ~1 7 q 1~ 1 wherein R, R1 and R2, which may be the same or different, may each be represented by one of the substituents of Group 2, p may be 0 or l; each R3 and ~4 may be independently represented by one of the subs~ituents of Group 3; n may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, lO, ll, 12, 13, 14, 15, 16, 17, 18, l9, or 20; Z is an element selected from the group consisting of carbon, sul~ur, boron, or phosphorus; q is an integer from 2 to 3 and r is an integer from l to 3, when Z .is C, q is 2; when Z is S, P or B, q may be 2 or 3; whQn Z is C or S, r is l; when Z is P or B, r is 2; R1 or R2 can be eliminated with OH to give a cyclic amide;
and physiologically acceptable salts of any andJor all of the foregoing.
Illustra~ive of oompounds of particular interest in this class are:
l. R1~H, R2=t-butyl, Z=S, q-3, rGl ~ ~o ~ p=
2O Rl=H, n=0, R2=l,2,3-trimethylcyclohex~l, Z=S, q=3, 3. R1-R2=R3-R4=H, ~=2, Z=S, q=3, r=l ~This compound is also referred to as taurine.) 4O R1=R2=R3=R4~H, n=2, Z=C, q=2, r=l, p=0 (This compound is also referred to as ~-alanine.) 5. R1=p-cyanophenylcarbamoyl, R2=R3=R4=H, Z=C, q=~, r=l, n=l, p-0 l`A21 1 7284 W~93/10677 PCT/US92/10179 6. R3=R4=R2=R1-H, n=2, Z=P, q--3, r=2, p=0 and physiologically acceptable sal~s of any and/or all of the foregoing.
M. As used herein and the appende~ claims the ~ollowing molecule shall be referred to as M-l and said molecule represents the general class of compounds having -~
the structure:
, N~
~E-l I N`
~ ~ ~ ~ / N~ 3 ¦~ R )p 0=5=0 wherein p may be 1, 2, 3 or 4, substituents R, R1 and R2, which may be the same or different, are each ~~
represented by one of the substituents of Group 1, in -~
: a~y combination and R3 i5 represen~ed by one of the ~- ; sub~tituants of Group 2, wherein R, R1, R2 and R3 may : be present in any combination, and physiolo~ically acceptable salts of any and/or all of ~: the foregoing.
~ n illustrative of compound of particular interest in this class is:
: 1. R1z~3-p~enyl, R2~H,.
and phy~iologicalIy acceptable salts of any and/or all of ~ the foregoing.
: N. A~ u~ed herein and the appended claims the following ~olecule shall be re~erred to as N-l and said molecule represents the general class of com~ounds havin~

WO 93/10677 C A 2 ~ ~ 7 2 8 4 P~/US92/10179 4 3 "`'?"~
the structure:
. ~ .
N-l ~ r 7~ ~ ~ ~

wherein p may be l, 2, 3, or 4; g may be l, 2, 3, 4, or 5; the substituents R1 and R2, which may be the ~-same or dif f erent are each represented }: y one OI the sub~;ltituents of Group 1, in any combin~tion, and physiologically ac ::eptable salts of any and/or all of the f or~going .
Illus~rati~re of compounds OI particular interest in ~-this class is the follo~ring molec:ule which as used herein and the appended claims shall be referr~d to as N-2:
. . . _ O. The general class of compour~ds compris- ng amino acids and poly amino acids.
This class includ~s but is not limited to:
~ . naturally occurring ~, ,B f y ~ ~ arld/or ~ ~
2. in general ~ amino acids ~nd~or :~.
3., unnatur~l amino acids and/or 4. peptides and poly amillo ac:id;s The nitrogen atoms OI these compounds may be substituted with one, two or t~ree substituents of Group 2,; as appropriate. If oxygen (O) or sulfur (S) atoms exist in these molecu~ es they may be substituted with an appropriat~ number of substituents from Group 2. Any aromatic groups in these compounds may be substituted with one or more of the substituents of W093/~677 C A 2 1 1 7 2 8 4 PCT/US92/10179 &roup 1 in any combination, and physiologically acceptable salts o~ any and/or all of the foregoing.
Illustrative of compounds of particular interest in this class are- -1. D-glutami~ acid, 2. D-aspart.~_ acid, 3. aminomalonic acid, 4. ~aminoethanesulfonic acid, S. ~-alanine, ~ 3,4-dihydroxyphenylalanine, 7. L-as~artyl-L-aspartic acid and physiologically acceptable salts of any and/or all of the foregoing. ; -P. As used herein and the appended claims the following molecule shall be referred to as P-l and said molecule representæ the general class of ~ompo~nds having the generalized structure: :-One ~killed in~the art will recogniza that this general structure twhich~would ~ot~likely exist) is a representation of several tautomers ~everal of which are repre~ented~by the follo~ing:
. .~ . .

¦ RlN \ 2 1 ~ \R2 ¦

WO 93~10677 C ~l 2 1 1 7 2 ~ 4 Pcr~usg2/1ol7g 1~ 5 ';

N Rl~ )J3CN

L
. _- ~ V .

.
wherein the substituents R and R3, which may be the ~a~e or differe~, are each repr~sent~d by ona of the substituents of Group 1, in any combination; pC1 and ~, which may be the same or different, may each be represented by one of the substituents of Group 2, in ar!y combination~ and A may be C, S, N, or O and when A
i~; C 1 substitution on this carbon may be made with one or more of th~ tituent~ of Grs:~up lt in any cs~mbination, when A is S or N substitution on this S
or N may be made with one of the sub~;tituants of Group 2, ~.
and physiologi ally acceptable salts of any and~or all of the ~or~going.
Illustrative of compounds of particular interest in this class are:
1. Xanthosine-5 mol~ophosphate 2. Inosine W093/10677 CA 2 1 1 7~ 84 PCTlUS92/10179 3. Guanosine and physiologically acceptable salts of any and/or all of the foregoing.
Q. As used herein and the appended claims the following mo~ecule shall be referred to as Q-l and said molecule represents the general class of compounds having the generalized structure~

One skilled in the art will recognize that this general structure (which would not likely exist) is a representation of several tautomers several of which are represented by the following: -~ :~
~:~ ~ 1 ~ A .

¦ N~ : R~ ~R2 ! ~:

¦ R5 N 3 - -- R5J~N R~ ¦
: :~

~ . .

~2 R6~ J~R2 ¦

¦ ~N R, ~ R~
~: ~ _ :R~ ~ _ R4 ,: ~ ' wherein Rl, R2, R3, and R~, which may be the same or different, are~each represented by one of the ~ substituents of Grsup 1, in any combination; R4 and R6, which may be the same or different, are represented by one of the substituents of Group 2, in C~ 2 1 1 72~4 WO93/10677 PCT/US92~10179 47 ~ ~i any combination, and A may be C, S, N, or O and when A
is C, ubstitution on thi~ carbon may be made with one or more of the substituents of Group l, in any combination, when A is S or N substitution on this S
or N may be made with one of the substituent~ of Group 2, and physiologically acceptable salts of any and/or all of the foregoing. ;;~
It will be recognized by one skilled in the art that :~
this class is intended to include any oxidation state of the ring system, as for example, hydrogenation of one or ..
more o f the do~ble bonds.
Illustrative of compounds of particular interest in this class are:
l. Orotic Acid 2. Dihydroorotic acid and physiologically acceptable salts of any and/or all of ~:
the foregoing. ::
R. Th~ class of c~mpounds commonly known as natural products. This class includPs but is not limited to:
alkaloids, terpines, monoterpines, diterpines, triterpines, sesqueterpines, fl~vanoides, chalcones,.
dihydrochalcon~s, humulones, lemonoids, saponins, : coumarins, isocoumarins, sinapines, steroids, flavinon.es, and physiologîca}ly acceptable salts o~ any and~or all of : the foregoing.
; : As used~h~rein:and the append d claims ~he following : ~ ~olecule shall be referred to as R-l, and said molecule exemplifies the general class of compounds having, but not WO93/1~677 C A 2 1 1 7 2 8 4 PCT/US9~/10179 . , ,. . -:
limited to the following stru~ture:
: .

' ' and physiologically acceptable salts of any and/or all of the foregoin~.
~s u~ed herein and the appended claims the ~ollowing -~
molecule shall be referred to as R-2 and said molecule represents the gen ral ala~s of compound~ having, but not limit~d to the following ~tructure: -~ ..

, and physiologically acceptable salt~ of any and/or all of the foregoing.
As used her~in and th~ appended claims the following ~-molecule shall be referred o as R 3 and ~aid molecule represe~ts the general cla~s of eompounds haYing, but not WO 93/110677 C A 2 1 1 7 2 ~ 4 PCI/US92/10179 limited to the following structure:
~ , ~' .."~

;~:

and physiologic:ally acceptable salts of any and/or all of the f oregoing .
As used herein arld the appended c:laims the following molecule shall be reerred to as R-4 arld said mol~c:ule repre ents the general class of compounds havi.llg, but not limited to the iEollowing structure: :
o 1~ .,.

: _ and physiologiczllly acceptable salts of any and/or all of the Poregoing.
As used herein and the appended claims the îollowing molecule shall be referred to as R-5 and said molecule W093/10677 CA2~ 172~4 PCr/US92/10179 represents the general class of c:ompounds ~aving, but not limited to the following structure:

and physiologically ac:c:eptable salts of any.. and/or all of `the f oregoing .
A~ used herein and the appended claims the following molecule shall be referred to as R-6 and said molecule represents the general class of compounds having, but not limited to the follc:~wi~g structure:

>~ ,.
H~ /~ :~

and physiologically ac:ceptable salts of any and/or all of the f oregoin~ .
As used herein arld the appended claims the following molecule shall be referred to as ~-7 ~nd said molecule '' CA2~ ~ 7284 WO93/10677 Pcr/l~592/10179 :~
5 1 ?;
represents the general class of compounds having, but not limited to the ~ollowing structure:
I - ~0 ~ ~

~ :

and phy~i ologically as~ eptable salts of any and/or all of the foreg~ing r A used herein and the appended rlaims the following : ~ : molecule shall be re~Eerxed to as R-8 and aid molecule ~:
represents the general ~ lass of compounds having, but not limited to the following structure:
~ o ~-~ : ..H ~
; ~ ~ .............. O H

and physiologically~ aaceptable salts of any and/or all of ~: the foregoing.
As used herein ~nd the appended claims the following molecule shall be referred to as R-9 and said molecule W~93/10677 C A 2 1 1 7 2 8 4 PCT/U~92/10179 52 :
represents the general class of compounds having, but not limited to the following structure:
,,.", ;
and physiolo~ically acceptable salts of any and/or all of the foregoing. .
~ As u~-d herein and t~ appended clai~s the following molecule s.all be referr~ - to as ~ .O and said molecz~ : :
represents the ~eneral cl~ss of c ..~ounds havin~, bu r.~t ~:: limited to the ~ollowing structur.
, ~ i(~ ~

~ , and physiologically acceptable ~alts of any and~or all of the foregoing.
, :
: ~s u d herein and the app~nded claims the following molecule shall be referred to as~R-l~ and said molecule represents the ge~eral class of co~pounds having, bu not : limited to the:follo~ing structure:
. .:
: ~ CH ~ ~ C=~ ::
X `1/ C~ C--C--N--(CH~)2 ¦

~: ~ ' :~
and physiologically acceptable salts of any and/or all of .

CA2 1 1 72~4 W093/10677 PCT/US92/10~79 53 .
the foregoing.
A~ used herein and the appended claims the ~ollowing molecule shall be referred to as R-12 and said molecule repre~ents the general class of compounds ha~ing, but ~ot limited to the following structure:

_ __ _ _ _. _ ~.
and physiologically acceptable salts of any and/or all of : the for~going.
As u ed herein and the appended claims ~he following molecule shall be referred to as R-13 and said molecule represents the g~neral class of compounds having, but not limited to the following structure:
_ ~0 ~ N 2 1~' o~c~o I ~`, and physiologically acceptable salts of any and/or all of the foregoins.
-.
, WO 93/10677 C ~ 7 2 8 4 PCl~US92/10179 ~s used herein and the appended clailus the following molecule shall be referred to as R-14 and said molecule ~:
represents the general class of compounds having ~ but not ~:
limited to the following ;tructure:
. .................. . . .

. ~
and physiologically acc:eptable salts of any and/or a}l of -:
the foregoing~
As used herein and the appended claims the following molecule shall be referred to as R-lS and said molecule represents the general c:lass of compounds having, but ~ot ~: limited to the Pollow~ing structure:
. , _ _.

~ ~ ~ .

and physiologically acceptable salts of any and/or all of . ~:
the foregoing.
P,s used herein and the appended claims the f ollowing molecule shall be referred to as P~ 16 and said mo~ ecule WO93/10677 C ~ ~ 1 1 7 ~ ~ 4 PCT/US92/10179 5 5 ,1~"
represents the general class of compounds having, bu~ not limited to the following structure:
~c~ """~ ~0~3 .,~

and physiologically acceptable salts of any and/or all of the foregoing~
As used herein and the appended claims the following molecule shall be referred to as R-17 and said molecul~
repreæents the general class of compounds having, but not li~ited to the following structure: ~
. . . . _ ., R~

:
:~and physiologically acceptable salt of any and/or all of the foregoing~
As used herein and the appended claims the following molecule sha.l be referred to as R-18 and said molecule represents the general class of compounds having, but not ~, -~ C~21 1 7284 56 :
; ~ i limited to the following structure: ~
_ _ _ ' [~
_ ,~
_ '~,',.

.

and physiologically acceptable salts of any and~or all of : the foregoing.
As used herein:and:~the appended claims the following ~:
~, molecule shall be~referred to as R-l9 and said molec~.le represents the:general;class of compounds ha~ing, b~l~ not limited~to:the fol~lowing structure~

~ i , , and physiologically~acceptable salts of any and/or all of -~
the foregoing. .
As used herein and the appended claims the following molecule shall~be referred to as R-20 and said molecule ,; ~ ' ' ~

W~ 93/1~677 C A 2 1 ~ 7 2 1~ 4 PCr/US~2/10179 57 .~, r~preæents the general class of coJnpounds having, but rlot limited to the following struc:ture:

and physiologically accsptable salts of any ancl/or all of the foregoing. ;
As used herein and the appended claims the followiIlg molecule shall be referred to as R-21 and said molecule rep:res~nts th~ general cl ass of csmpounds having, but not limited to the following structure:

~b ~

;: :
and physiologically accepta~le salts of any and/or all of the f oregoing .
As used herein and the appended claims the following .
molecule shall be referred to as R-22 and said molecule W093/tO677 PCT/US92/10179 : CA21 17284 58 repre ents the general cla~s of compounds haYing, but not limited to t~e following structure: `
. . . . ,. ................. .. ~
~ . ~

and physiologically acceptable salts of any and/or all of th foregoing.
As used hereîn and the appended claims the following ~-molecule shall be referred to as R-23 and said molecule repre~ents the general class of compounds having, but not limited to the following structure: ~.

and physiologically acceptable salts of any and~or all of the f oregoing.
As used herein and the appended claims the following .
molecule shall be referred to as R-24 and said molecule WO93/10677 C A 2 1 1 ~ ~ 8 4 PCT/US9~/10179 59 : .
r~presents the general class of compounds ha~ing, but not limited to the following structure:

and physiologically acceptable s~l~s of any and/or all of the foregoing, As u~ed herein and the app nded claims the foilowing molecule shall be referred to as R-25 and said molecule represents the general class of compounds having, but not limited to the following structure: -and physiologically acceptable salts of any and/sr all of the foregoing.
As used herein and the appended claims the following molecule shall be referred to as R-26 and said molecule W093/10677 ~ A 2 1 1 7 2 ~ 4 ~CT/US92/10179 represents the general class of compounds haYing, but not limited to the following structure:

and physiologically acceptable salts of any and/or all of the foregoing.
As used herein and the app~nded claims the following molecule shall be raferred to as R-27 and said molecule ~:
repr~sents the general class of compounds having, but not limited to the following ~tructure:
... . . . - . . . .
0~

and physiologically acceptable salts of any and~or all of ~he foregoi~g. :
As used herein and the appended claims the following molecule ~hall be referred to as R-28 and said molecule WO93/10677 C~ 8 4 PCT/USg2/aol79 - represents the general class of compounds having, but not lîmited to the following tructure:
,~
~ 3~ o-~lu~O~ j and physiologically accep able salts of any and/or all of ::
the *oregoing.
As used hereîn and the appended claims the following molecule shall be referred to as R-29 and said molecule .
represents the general class of comp~unds having, but not limited to the following structure:
_ _ . . ................... . ... ~:
~- ~ ,L

.
' and physiologically acceptable salts of any and/or all of ~:
: ~he foregoing.
As use~ herein and the appended claims the following molecule ~hall be referred to as R 30 and said molecule : , .
.

WO93/106~ ~ 2 1 1 7 2 ~ 4 PCT/U~9~/10179 . 62 represents thP general class of compounds haYing~ but not limited to the following structure~
.. _ . ,' 0~011~ ' ~

¦H0 ~ ~

"~' and physiologically acceptable salts of any and/or all of the foregoing.
As used herein and the appended c:laims the f ol~owing molecule shall be referred to as R-31 ancl said molecule represents the general class of compounds having, but not limited to the foIlQwing stnlcture ~
: : . ~ ~_ _ ,:' ~ U~ 81~

~/ ,.. _ __ _ and phyiiologically ac::c:eptable salts of any and/or all s:~f the f oregoing, :
As us~id herein and the appanded claims the following molecule shall be ref~irred to as R-32 and said molecule .

w0 93/io677 ~ 7 ~ 84 PCT/US92/10179 ~
63 , represents the general class of compound~ having, but not -`.
limited to the following structure~

and physiologically acceptable salts of any and/or all of ~he foregoing.
As used herein and the appended claims the following :`
molecule shall be referred to as R-33 and said molecule represents the general class of compounds having, but not ``
limited to the following structure:
.

~:
. . / .,_ : ~
~, and physiologically accPptable salts of any andJor all of : the foregoing, ~ s u~ed herein and the appended claims the following molecule shall be referred to as R-34 and said molecule ;~
- :

WO93/10677 CA~l 17~ PCI/U~92/101~9 : --. ~4 ~:
repre~entC the general class of s~ompounds having, but not limited to the ~oll~wing structure:
_ ,.
~ ' , .:

and physiologically acceptable salts of any and/or all of the f oregoing .
As used herein and the appended claims the following molecule shall be referred to as R-35 and said molecule `~
represent~ the general class of compounds having, but not limited to tike follc)wing structure:
_ _ .

~1 and physiological1y acceptable~ ~alts of any and/or all of the f oregoing ~ : :
As used h~rein and the appended claims the following ms:lec:uIe shall be~ ref~rred to as R-36 and said molecule represents t~e general ` class of compounds having, but rlot ~ -: :.

~'~

;:
-, WO93~10~77 ;~ 7~ 8~ PCI/l~S92/~179 ,..~
limited to the following structure: : -and physiologicaIly acceptable salts of any and/or all of the foxegoing.
The above examples and other natural lproducts of this la~3s may be tra~s~c)~med (as per the usage OI this term de~ined above) to additional tastands by a variety of ch~mical modifications. Thus, we envi~age additional tastands in which the above examples s:an be ~odif ied b~ -variation of 'che ~alency or oxidation state of any carbon atomf in which; epoxides may ~e opened by oxidation or nucleophilic ~ubs~itution or may be reduced to alcohols, in which lactones may be Gonverted tc~ hydroxy acids or hydrc3xy acids may be cyc:lized to lactones, or in which enol tautomers ~re converted ts:~ the appropriate keto tautomer.
~urth~rmore, the rlng systems depicted in the abvve ::
~xa~pIes may be substituted with a variety of aliphatic, ~
alicy~:lic, aroma~ic gr~ups, hydroxy, amino, or other ~ ;:
substituents of group 1 or 3, as def ined above, and hydroxyl, amino or thio groups may be substituted with one of ~he substituents of group 2, as def ined above ~ The ~ `
stereochemical relationships of the iubstituents laay be is or trans, and chiral centers may be of R or S
conf iguration . In all exampl~s nitrogerl or oxyg n atoms may be substituted with group 2, substituents or mono or polysaccharic~es including but no~ restricted to those WO 93/10677 CA 2 1 1 72~4 PCl`/US92/10179 indicated in the above examples.
Illustrative of compounds of particular intere~t in this c:lass are the following:
As used her~in and the appended claims the following molecules shall ~e referred to as R-37 ~

J J, I .
~ 0 0R~

where:
1- R~ D glc:, R2=a-L-rha 3-Me, 2. Pc1~1-D-glcZ~-L-rha, R2=H
and physiologically acceptable salts of any and/or all of the foregoing.
As used herein and the appended claims *he following ,:

7 ~ 8 ~
W093~10677 PCT/US92/10179 67 ~ -molecule shall be referred to as R-38: -~
. _ . .

.
. `'.~ ;~
and physiologically acceptable salts of any and/or all o~ the foregoing.
~ ~ As used herein and~the appended~claims the following : molecule~ shall be`;referred to as ~-39:

~: ~ ~,X
- , ; .
:~
: H
~ 2 ~H - X ~ \ ~ ';
: ~ ~1-R2-H. X~O g~ .`
R1~)H. R2~H. X~H2 _ R1~0H, R2~0Ac, X~H2 and physiologically acceptable salts of any and/or all C~ 2 1 1 7284 WO 93/10677 PCr/US92/10179 of l:he oregoing.
As used herein ~nd the appended claims the following molecules shall be referred to as R-40:

R1 ~R2YH . X- \
OH
R~ OAC, R2~H ~ X~H2 R, ~ R2~OAC ~ X ~ H2 and physiologica~ ly ac:ceptable salts of any and/or all of the foregoing7 As used herein and the appended claims the following molecules shall be re~exred to as R-4 1: ..

J ~ :

~..
R ~H

and physiolc)gic:ally acceptable salts of any and/or all of ~he foregoing.
As used herein and the appended claims the following W093/10677 ~ 4 pCT/~9~/10179 69 ,~
molecule ~hall be referred to as R-42:

L~ ~
,~
and physiologically acceptable salts of any and/or all of the foregoin~
As used herein and the appended claims the following mo~ecule shall be referred to as R-43:

,:
' ,'.

and physiologically acceptable salt~ of any and/or all o~ the foregoing.
~: As used herein and the appended clai~s the following `~-: molecule shall be referred to as R-44~
:: ~, .
~ .
~ and physiologically acceptable salts of any and/or all :: of the ~oregoing.
As used herein and the appended claims the following _ _ _,,, _,, ~, _, . _ .. _ .. _ . T-- _ .-- -- ' -- ' ' WO93/10S77 C A 2 ~ 1 7 2 8 4 P~T/U~92/~179 molecule shall be referred to a~ R-45:
.. -- ~

O . I

/~

and physlologically acceptable salts of any and/or all of the foregoing.
As us d herein and the appended claims the following molecule shall be referred to as R-46: ,-, . ._ _ ~: : .. ,,,' i ~i ¦ COOH

and physiologically acceptable salts of any and/or all of the foregoing.
As used herein and the appended claims the following . ~,.

8 ~
W~93/1~677 P~/US92/10179 - molecules shall be referred to as R-47:
.. . .. - _ .
~ ~C O O H j R~DH
~ 'I

R~ RR5~0 ~ R2-R3~H ,R"~ OH :~
Rl~R~-,8 OH, R2R,~H, RS~O
R~ ~R5~0 P~2~R3~H, R~-c3H
R~O. R2~0H. ~3~ H~ RS~ O~H
R ~ n - O H, R 2 - R " ~ H, R 3 ~ S ' O
'~"
and physiologically acceptable salts of any and~or all o f the~i foregoing O - .
As used herein and the appanded claims the following molecule hall be re~erred to as R;48:
~'~

.-~

and phy~iolosically acceptable salt~ of any and/or all of the foregoing.
As used herein and the appended claims the following ~.~

WO93J10677 CA 2 1 1 72 8 4 PCT/USg2/}0179 molecule shall be referred to as R-4~:
. . ~ _ ~ r~

and physiologically acceptable salts of any and/or all ;;.
of the foragoing.
As used herein and the appended claims the following ..
molecule shall be referred to as R-50:
. . ...................... _ _ ,, .

; ~ and physialogically acceptable salts of any and/~- all of the ~or~oing~.
~ As used herein;and the appended claims the follo~.ng :~
:~ molecule shall:b~ referred to as:~-51:
I

and physiologically acceptable salts of any and/or all wo 93/10677 CA ~ 1 1 i 2 ~ 4 PCI/US92/10179 7 3 ;~
of the f oregoing .
As used hersin and the appended claims the following molecules shall be referred to as R-52: :
._, . . . , /~\ ! I /~='\
~C C ~0 C H ~ ..

OH :~
R
R ~ 3-OH `~;
R ~ 3-OCH3 ~:~
R ~ O C H 3 :~
R 3, 4-d i -OCH3 ::
~3-CO0~2~s :;~
R~ 4-GOOC2H~, :
R 3 C11~50H
R 4 ~ tl 2 H
R ~ 4 ~ C I :
-.-and phy iologic:ally ~cceptable salts of any and~or all :: of the f oregoing .
As u~ed hexein and the appended claim~ the following :
molecule sha}l be referred to as R-53:

c--c ~ o ~ . .
H I / I H ~ H ~:

~ \N ~

and physiologic:ally acceptable salts of any and/or all of the ~oregoing.
As used herein and the appended c:laims the following ,, W093/10677 CA2] ~ 7284 P(~/US92/1û179 ~: 74 molecule shall be referred to as R-54: -1 ~2~H
~ ,'':' ~ O-G I U-0 2'~

, `-and physiologically accepta~le salts of any and/or all of the f oregoing . . .
As used herein and ~he appended claims the following molec:ules shall be referred to as R-55: 1:
, _ :

~~-OH, R2~11, 2~CH~O~I, iR~,.CHa IR~.~ OH, R2~H, R~CU20-Clc--Clc, IR~CNy 1~1 ~a-OH, R2~H, R3~CH20-G I c, R~CH, Rl~O, R2~H, R~OH, R~CH~
~ O, R2~14, R3~CH20-Clc-CI:~, R~CH
R~ 2D~o, ~ H20--GIo. ~~H3~
~ p-OH,' ~2~Hf ~C~ 4'~ H2~
R 1 - O , R 2 W ~ I c , R3 ~ C H ~ , R 4 ~ C ~2 - - ~ l e ~ ~ ~ ~2~N, R~CH~, R6~CH2-O-~ I e~ ~^~
~ l c ~ g l t~ c o p ~ n ~
~ - -and physic:~logically acceptable ~alt~ of any and/or all of the foregoing.
S. The c:lass OI compounds having the struc:ture, or structures clo~ely related to the following molecule which ~1 1 12`~4 WO93~10677 PCr/USs2/10179 ~
as used herein and th~ appended claims shall be refarred to as S-l:
.. . . - ~ ~ ~.

~ ~ R5 ~
5~

''.:.`
wherein R1, R2 ~ R3, and R4 which may be the same or :~
different are each designated by one of the substituents of Group 1. ~ is represented by one of the substituents of Group 2, and R6 is represented by one of the substituents o~ Group 3, wherein Rl, R2, R3, R4, ~, and R6, may be present in any ~ombination, and physiologically acceptable salts of any and/or all of ~he foregoingO ~ ~
Of parti ular interest is the compound ha~ing the ~ :
structure (commonly known as epihernandulcin~: :
.__ . . ~ , ~
~ ~ ~\~ ~

~ T. Th~ clasæ of compounds having the structure (or : ~ .

:

W~93/10677 ~4 PCT/US92/10179 : i 76 structures closely related to) which as used herein and the appended claims shall be referred to 2s T-l:
. ~

~-1 wherein p may ba l, 2, 3, 4 or 5; R1, which may be the same or different, are each represented by one of the substituents o~ Group 1 in any combination; R2 and R3, which may be the same or different, are each repre~ented by one of the substituents of Group 2;
each R4 and Rs may be independently represented ~y one ~:
of the substituents of Group 3 and wherein R1, R2 g~ -R4, and R5 may be present in any combination; n may be 0, l, 2, 3, 4, 5, 6, 7, B~ 9, lO, ll, 12, 13, 14, 15, 16~ 17, 18, 19, or 20; Z may be an element selected : from the group c~nsisting of carbon, sul~ur, boron, or phosphorus; q is ~n integer from X to 3 and r is an integer from 1 to 3, when 2 is C, q i~ 2; when Z is S, :P or B, q may be 2 or 3: when Z is C or S, r is l; ~:
when Z is F or B, r is 2;a nd phy iologically acceptable salts of any and/or all of the foregoing.
Illustrative of compounds of particular interest in this class are:
l. R2-R~=*=R5-H, n=2, R1=p-cyano t Z=C ~ q=2 r=l, p=l 2. R2=R3=R4zR5=H, n=2, Rl-p-nitro, Z=C, q=2, r=l, p=l 3. R~=p-cyano; R2=~=R4=R5=H, n=l, Z-P, q=3, r--2, p=l 4 R1=p-nitr~; ~2=R3=R4=R5=H, nol, Z=P, q--~, r=2, p=l R1=p-cyano; R2=R3=R4=~.5=~, n 1, Z-S, q=3, r=l, p=l 6 R1=p-nitro; R2=R3=~4-R5=H, n=l, Z=S~ q=3, r=l, pcl and physiologically acceptable salts of any and/or all of the foregoin~.
U. The class of compounds having the structure (or :

WO93/10677 C ~ 2 1 1 7 2 ~ 4 PCT/VS92/1017~
77 , 5c,,, structures c105ely related to) which as used herein and the :~
appended claims shall be referred to as U~
. . ~ ......... . . . ...... .. . ' U-l ~ R~ I .
~"~ ~

~.
wherein A may be O(oxygen), S(sulfur), or C(carbon~, :
and when A is C, n is l and wh n A may be O or S, n is zero; ~ , R2, R3, R4, R5, R6, ~7, R8 R9 ~10 R11 a d R12 which may be the ~ame or differ~nt, and which may be pre ent in any combination, may each be repr sented by one of the following: one of the substituents of ~Gr~up l~ o~R13,~ NH-R13, N-(R13)2, or S-R13, where Rl3 is represented by one of the substituents of "Group 2"; -~
~r two R substituents may be dehydrated to form an : anhydride linkage;:or two R s~bstituents ~ay form a cyclic structure, and phy~iologically a¢eeptable salts of any and/or all of the for~going. ~-~
o~e skilled in the art would recogniæe the six msmbered (pyranose) rings of this class may isomerize to five membered (furanose3 rings as is w~ll known for many sugars.
Illustrative o~ compounds of particular interest in this class are:
1. 6-chloro-6-deoxytrehalose, -~
2~ 61,6-dichloro-6',6-dideoxytrehalose, 3. 6-chloro-6-deoxy-D-galactose, 4. 6-chloro-6-d.eoxy-D-mannose, W093/l0677 CA21 1 72~4 PCI/US92/10179 78 ~:~
S. 6-chloro-6 deoxy-~-mannitol, 6. methyl-2,3-di-(glycyl-glycyl)-~-D-glucopyanoside, 7~ methyl-2-0-methyl-~-D-glucopyranoside, 8. methyl-3-0-~ethyl ~-D-glucopyranoside, -~
9. methyl-4-0-methyl-~-D-glucopyranoside, 10. met~yl-6-0-methyl-~-D-glucopyranoside, 11. 2,2'-di-0-methyl-~ trehalose, 12. 3,3'-di-0-methyl~ trehalose, 13. 4,4'-di-0-methyl~ -trehalose, 14. 6,6'-di O-methyl~ -trehalose, 15. 6'-0-methylsucrose, 16. 4'~ methylsucrose, 17. 6,6l-di-0-methylsucrose, 18. 4,6'-di-0-methylsucrosP, -~
19. 1,6'-di-0-methylsucrose, 20. cyclohexane 1,2/4,5 tetrol, 21. (~)-cyclohexane 1,3,4/2,5 pentol~(~)-proto .~;
quercitol], 22. (-)-cyclohexane 1,3,4/3,5 pentolt(-)-vibo ~uercitol]~
23. cycl~hexane 1,2,3/4,5,6 hexol ~neo Inosit~

24. cyclohexane 1,2,3,5/4,6 hexol tmyo Inositol~,

25. cyclohexane 1,2,4,5~3,6 hexol [muco Inositol],

26. methyl-~ D-arabinopyranoside,

27. met~yl-3-deoxy~ D-arabinohexopyranoside, 2~.~ 3-deoxy-~-D-arabinohexopyranosyl-3-deoxy-~-D
arabinohexopyx~nose, 29. 2-d~o~y~ D-ribo hexopyranosyl-2-deo~y-~D
ribohexopy~a~ose, 30. 3-deoxy-a D--ribo-hexopyrano yl-3-deoxyf-~-D-ribohexopyranose, 31~ 1,6-anhydro-3 dimethylamino-3-deoxy-~-D- .
glucopyranose, ..
32. 1,6-anhydro-3-dimethylamino-3-deoxy ~-D~ , ~
al~ropyranose, ~:
33. 1,6-anhydro-3-acetamido-3-deoxy~-D- . -glucopyranose, 34. 1,6-anhydro-3-acetamido-3-deoxy-~-D-gulopyranose, 35. 1,6-anhydro-3-amino-3-deoxy-~-D-gulopyranose, WO93/10677 CA ~ 1 ~ 72~4 79 PCT/US92~10~79 36. methyl-3,6-anhydro-~-D-glucopyranoside, 37O 3,6-anhydro-~-D-glucopyransyl-3,6-anhydro-~-D- ~
glucopyranoside, :
38. 3,6-anhydro-~-D-glucopyransyl-3,6-anhydro-~-D- ..
fructofuranoside, ~
39. 3,6-anhydro-~-D-glucopyransyl-l,4:3,6-dianhydro- .
~ -D-fructofuranoside, and physiologically acceptable salts of any and/or all of the foregoing. ~:
V. The class of compounds having the structure (or .:
structures closely related to) which as used herein and the appended claims shall be referred to as V~
, . . .
. ~:

( R ) p ( y ) ~ ( A ) 1--( Y ) ~--( R ' ) q . ( A ) a : l ~, ~:~ : : :
- :"

V~
wherein a, r,:~l, and m may be O or l; n, j, and k are O, 1, 2, or 3~;~ea~h R2 and R3 which may be the same or different independently may each be represented by one .~:.
: ~ of the sub~tituents of group 3; Y tWhich may be the ;:
same or different) may be N (nitrogen), O (o~ygen), or ; 5 ~sulfur); when r. or m is 1 and Y is N, p or q may be 2 or 3, when r or~m is 1 and Y is O, p or q is l; when ~: r or m is 1 and Y is S, p may be 1 or 2; A may be H, C=O, O-S=O, S=O, O=P~H~OH, O=P(OH)2, or O=B(H)OH; Q is represen~ed by one of the substituents of Group 3; R
which may be ~he same or d}ff rent when p>l) and R' (which may be the same or different when ~1) are ~-~
~, wo g3,l0677 C A 2 ~ 1 7 ~ 8i4 PCr/l~S92/10179 ! 80 represented by one of the substituents of Group 2 or one of the following three structures (as used herein and the appended cl aims the structures shall be referred to as V-2 ) in any combination and th~ :
appropriate stereoc~emistry:
Q---C CR2R3) f--C~ C A) b--Z
V-2 ~)c ... Z .~

2R3~f C-- -~ A~ b--Z
R
:~
Q

¦_ ~ C R ~ ( Y ~ d- ~ A ~ b--~ R ~ e l wher~in Y (which may be the same or different) may be N tnitrogen), O (~oxygen), or S (sulfur3; when d is 1 and b i~; 0 ànd Y is N " e may be 2 or 3, when d is and b is 0 and Y is O, e is l; f may be 0, 1, 2, 3, 4, 5, 6, 7 ;, 8, ~9, 10; when d is 1 and b is 0 and Y is S, -e may be 1 or 2; A may be H, CoO, O--S=O, S=O, O=P~H)OH -;
or O=P(OH)2, O=B(~OH; Q is repre~ented by one of the substit~aent of Group 3; R~ and Q together may f orm a cyelic structure; any of the R3 ' s and Q together may form a cyclic structure; any of the R3 ' s and R"~ s together may form a cyclic structure; b may be 0, 1, or 2 and c may be 0 or 1; Z and Z ' are the same or : .
different and ~are represented by ~H, -O~X~, OPc", NH~
NHR", N (R~ ) zj; Rl' may be alkyl, branched alkyl, aryl, - -aralkyl, alkaryl, cycloal3cyl, substituted alkyl, :~
substituted cycloalkyl substituted aryl, substituted aralkyl, su~s ituted alkaryl, and R"' may be alkyl, wo 93/10677 C A 2 1 1 7 2 ~ 4 PCT/VS92/10179 ;;

branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain ~e.g. one of thP 20 common amino acids), X~ may be H~ or a physiologically acceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cation, and physiologically acceptable salts of any and/or all of the foregoing.
Illustrative of compounds of particular interest in this class are:
1. N-(L-aspartyl)-p-aminobenzenesulfonic acid, 2. N-(aminomalonyl)-p-aminobenzenesulfonic acid, 3. amino ethane phosphoric acid, 4. N-~N-(p-cyanophenylcarbamoyl)-L-aspartyl]-p-aminobenzenesulfonic acid, 5. N~-L-aspartyl)-l-aminocyclopentane-l-carboxylic acid, , , 6. N(-L-aspartyl)-1-aminocyclopropane-1-carboxylic acid, 7. N~-L-aspartyl)-1-aminocyclooctane-1-carboxylic acid, 8. N(-L-aspartyl)-l-aminocyclohexane-l-carboxylic acid, 9. N(-L-aspartyl)-2-aminocyclopentane-1-carboxylic acid, and physiologically~acceptable salts of any and/or all of the foregoing.
W. The class of compounds having the structure (or ' ' ~.

WO 93/10677 ~ 7 ~$~ PCr/US92/10179 stnlcture~; elosely related to3 which as used herein and the appended daims ~;hall be referred to as ~-1:

W~ 1 wherein r, l, and m may be O or 1; ~, and k ~ay be 0, 1, 2, or 3; each R2 and R3 whicb may be the ~ame or slif ferent ind pendently may each be represented by one o~ lth~ subsl:ituents of group 3; Y (which may be the ~;ame or different~ may be N (nitrogell), O (oxygen) ~ or ~.
S ~sulfur); when r or m is 1 and Y is N, p or q may be 2 or 3, . when r or m is l and Y is O, p or q is l; when ;~
r or ~ is 1 and Y is S, p may be 1 or 2: A ~aay be H, C-O, O=SzO, S=O, O=PIH)OH, O=P~I)2, or O=B~H)OH; Q is represented by one of the ~;ubstituents of Group 3; R~
and Q toge~her may form a ~y~lic E;tructure; any of the R3's and Q together ~ay form a cyclic structure; any ~.
of the R3 ' s and R"' together may form a cyclic ctructure; R (which may be the same or different when p>l) and R' (which may be the same or different wher q>l ) are represented by one of the substituents of Group 2 or one of the following three structures ~as used herain and the appended claims the structures shall be re~erred to as W-2 ) in any combination and W093/10677 CA~l 17~84 PCI`/US92/10179 ~ 3 ~s~,~
the appropriate stereochemistry ~
. . ~:

- ( C R 2 R 3) f--C C A ~ b Z

W-2 z/ .
''``'''' Q

C C R 2 R 3 ) f C--- C A ) b--R :
.
Q
l ~ CR2~3~ CY)d-cA~b--cR~el ~ ~

: ~.
- ~, wherein Y (which may be ~he same or dif ferent) may be ~ ~ ~
~ ~ N !nitrog~n), (oxygen), or s (sulfur); when d is 1 .~
and b is 0 and Y is N, e may be 2 or 3, when d is 1 :~
and b is O and Y is O, e i~; l; f may be O, 1, 2, 3, 4, - ~;
5, 6, 7, 8, 9, }0; when d is 1 and b is O and Y is S, ~-e may be 1 or 2; A may be H, C=O, O-S=O, S=O, O=P(H~O~ ~-or O-P(OH)2, O=B(H):OH; Q is repr~sented by one of the substituents of Group 3; b may be O, 1, or 2 and c may . :~
be O or l; Z and Z': are the same or di~ferent and are ~:
represented by~ OH, -0~~, ORN, NH2, N~V ~ N(R" ~2~
may be alkyl, branched alkyl, aryl, aralkyl, alkaryl t cycl~3alkyl, substituted alkyl, substituted cycloalkyl substituted~ aryl~ substituted aralkyl, substitut d alkaryl, and R"' may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cyaloalkyl, s~stituted aryl, substituted ;~
aralkyl, substituted alkaryl, or an amino acid ~ide chain (e.g. one of the 20 common amino acid ), X~ may be H~ or a physiologically ~cceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cati on, WO93~10677 ~ 3 ~7 PCI`~US92/1017g 8 4 `;
and physiologically acceptable salts of any and/or all of the foregoing.
Illustrative of compounds of particular interest in thi~ class are: :
1. L-ornithyl-taurine 2. L-ornithyl-~-alanine .-3. L-lysyl-taurine 4. ~-diaminobu~yryl-taurine 5. L-diaminobutyryl-~-ala~ine 6. L-diaminopropionyl-~ alanine 7. L-diaminopropionyl-taurine 8. L-ly~yl-~-alanine 9. L-methionyl-taurine 10. L-methionyl-~-alanine 11. N-tL-ornithyl-)-p-aminobenzenesulfonic acid anld physioloa~cally acceptable salts of any and/or all of the foregoin~ :
~. The general class of compounds commonly referred to as chelators. These are molecules capable of chelating ~:
with, binding with, co~plexing with or ~oGrdinating with me~al ions. Included in this class are the physiologically : accept ble ~alts of any and~or all of the for~going~
Illustrative of compounds of particular interest in this class a~e:
1. E~hylenediaminetetraacetic acid (EDTA) and physiologically acceptable salts thereof~
2~ Ta ~ aric acid and physiologically acceptable salts `-th~reof. ~ ; -3. Lactic acid and physiologically aeceptable salts th~reof.
4. Ascorbic~acid and physiologically acceptable salts thereof. :
It should be understood that the present invention con~emplates the use of chelating agents that have varying degrees of affinity ~or met~l ions relative to the above listed compounds. Many of these more or le~s effective compounds are listed in A through W hereinabove. ~ few ~;
illustrative examples are:
1. 2,4-Dihydroxybenzoic acid, . .i 2. 3,4-Dihydroxybenzoic acid, 3. ~-Amino acids, 4. ~-Hydroxy acids, 5. peptides, 6. sulfonamides, 7. ~-Amino acids, and physiologically acceptable salts thereof.
Y. Tastand Enhancers: The ef~ectiveness of any ~;
individual tastand as described in Classes A-X may be enhanced by one surfactant while the same surfactant may lessen the effectiveness of other tastands or not affect that particular tastand at al}.
Illustrative examples of surfactants: .
l. tergitols 2. pluronics 3. poloxamars . ~
4. quaternary a~moni~m salts ..
5. sorbit~ns 6~ trit~ns :~
7. polyoxyethene ethers 8. sulfonic acid salts Surfactants can increase the effectiveness of some tastands r~
while the same:surfactant may lessen the effectiveness of other tastands or not~affect that particular tastand at :all. Surfactants~may: affect each tastand differently. The surfactant that affects~one particular tastand in a positive, negative or~neutral sense may affect another :tastand differently~ (i.e. a positive, negative or neutral sense and not necessari}y in the same way).
Z~ Tastand:Model: In l967, Sha}lenberger and Acree (Nature (London) 1967,;216, 480-4B2; which is hereby inco~porated by referènce) proposed that all compounds that elicit a sweet taste::response possess an AH, B system (AH
being a hydrogen bond donor and B being a hydrogen bond acceptor3 separated ~y about 0.28 to 0.40 nm. In this theory, AH was OH or NH and B an oxygen atom in groups such as CO2H, SO2H, SO2, CO, NO2, ~he nitrogen atom of CN, or even a halogen. For instance, in L-aspartyl-L-phenylalanine methyl ester the NH3~ is the AH and the COO~ is the B. They .

CA21 l ~2~
WO93/10677 PCT/USg2/10179 suggested that such compounds interacted with a sweet receptor by a pair of reciprocal hydrogen bonds ~a complementary AH, B system). This theory was widely accepted by most of the researchers in the field.
In 1972, Kier tJ. Pharm. Sci. 1972, 61, 1394; which is hereby incorporated by reference) expanded on the model of Shallenberger and Acree and proposed the existence of a third binding site which involved a hydrophobic interaction, which he designated as X. A molecule which would interact with all three (AH, B, and X) would be a --higher potency sweetener than one which only interacted with the AH, B site. Ariyoshi (Bull. Chem. Soc. Japan, 1974, 47, 326-330: which is hereby incorporated by reference) alid van~der Heijden ~Feed Chem. 1978, 3, 207;
which is hereby incorporated by reference) added ;
configurational restraints for the X group, that resulted -in assigning a 5.~5 nm spacing for the B and X sites and a 3.5 hm separation for the AH and X sites. This model has -become widely accepted~and~has been studied extensively by a number of researchers including Goodman and co-workers, Temussi and co-workers, Tinti and Nofre and co-workers, and Belitz who has also ~tudied the requirements for bitter ~-response in his modeling systems.
Goodman (Sweeteners, ACS Symposium Series 450, Chapt. `
10, 128-142; which~is~hereby incorporated by reference) has further refined the requirements necessary for a molecule to elicit a swe-t~respon6e by developing three dimensional requirements for thé~AH, ;B, X system. ~inti and Nofre ~Sweeteners, AC~S symposium Series 450, Chapter 7 and 15:
which are hereby incorporated by reference) have identified a fourth primary binding site which they call "D" (they refer to the "xn site as "G") and four secondary binding sites (Figure 1). The D site in a sweetener is a hydrogen bond accepter group and appears to be particularly effective when this group is a -CN or a -N02 group. Using this 8 centered model, they have developed extremely potent sweeteners which interact with all four primary sites and several secondary sites.
Goodman (J. Am. Chem. Soc. 1987, 101, 4712-4714; which WO93/1~77 C A 2 1 1 7 2 8 4 PCT/US92/10179 87 ~
is hereby incorporated by refe~ence) reports that the four stereoisomeric tetramethylcyclopentane compounds; L-aspartyl-L-alanyl-2,2,5,5-tetramethylcyclopentyl amide, L-aspartyl-D-alanyl-2,2,5,5-tetramethylcyclopentyl amide, N-(L-aspartyl)-N'-~tetramethylcyclopentanoyl)-(S)-l,l-diaminoethane and N-(L-aspartyl)-N'-(2,205,5-tetramethylcyclopentanoyl)-(R)-l,l-diaminoethane, present a unique opportunity to study structure-taste relationships.
Small changes in the overall topology affect the taste of these analogs (the ~,L amide is bitter while the L,D amide and the retro-inverso analogs are intensely sweet). In -~ddition, the bulky tetramethylcyclopentane group greatly decreases the conformational mobility of the peptide, allowing for a more complete analysis by NMR. With the assumption of a trans peptide bond and a nearly planar zwitterionic ring for the aspartyl moiety, the structure of -the compounds can be determined from an extensive conformational analysis by NMR. The coupling constants, NOE
values, and temperature coefficients used in defining the conformations of the four molecules were reported. The preferred mi~imum energy conformations are shown in Figure 2. Based on the results of this conformational study, Goodman proposed a model for sweet tasting analogs which contains elements of the models proposed by Kier, Temussi, van der ~eijden, Tinti and Nofre,~ and Shallenberger and Acree. The conformation of a sweet molecule can be described as possessing an "L shape", with the A-H and B
zwitterionic ring of the aspartyl moiety forming the stem, and the hydrophobic X (G in the Tinti-Nofre model) group forming the base of the L (Figure 3). Planarity of the molecule in the x and y dimensions is critical for sweet taste, substantial deviation from this plane into the z dimension is correlated with tasteless (~z) or bitter (-z) molecules. The existence of the aspartyl zwitterionic ring cannot be proven conclusively but can be assumed a priori on the basis of evidence obtained from NMR experiments. The Ca-C~ bond of the a6partyl residue pos~es~es a staggered conformation with the carboxyl moiety and the amino group in the gauche position and the sp2 plane of the terminal WO93/10677 r ~ 1 1 7 ~ ~/US92/10179 aspartyl carboxylate carbon atom and the Ca-C~ bond coplanar. These conditions are conformationally favorable for the formation of the zwitterionic aspartyl ring.
The X-ray structure of L-aspartyl-L-phenylalanine methyl ester has been solved by Kim (J. Am. Chem. Soc.
1985, 107, 4279; which is hereby incorporated by reference~. Crystallization was achieved in the tetragonal space group P41 with four L-aspartyl-L-phenylalanine methyl ester ~olecules and one water molecule per unit cell. The molecule shows an extended conformation with trans peptide bonds. However, the~phenyl ring is perpendicular to the peptide backbone and not coplanar with the zwitterionic ring of aspartic acid as would be predicted for a sweet dipeptide. This twis~ing of the phenyl ring is due to ~-packing fcrces within the crystal structure which result in stacking of ~djacent L-ospartyl-L-phenylalanine methyl ester molecules into stable columnar structures. The isolated molecule fro~the crystal structure can be rotated 40 about the ~" bond, to achieve an isoenergetic conformation in which~the rings are coplanar. This ~conformation correlates~ closely to our proposed model for ~; the structure of~sweet~dipeptides in solution (Figure 3).
Of coUrse, in solution the L-aspartyl-L-phenylalanine methyl ester moleoule ;is solvated and devoid of packing forces. Thus, the ~inherent flexibility of this linear peptide will easily accommodate the "L-shape" conformation required by the model~. Figure 4 depicts L-aspartyl-L-phenylalanin~ methyl ester in the L "shape" required for sweet taste in the~Goodman model superimposed in the 8-centered Tinti and Nofre model. In this configuration the ~`~
NH3~, C00~,-and `phenyl ring fit well into the AH, B and G
sites required for~a sweet taste in the Tinti and Nofre model as well as the AH, B and X sites of the Goodman model.
Belitz (ACS, Food Taste Chemistry, 1979, 93-131; which is hereby incorporated by reference) describes minimum requirements for bitter taste perception as a molecule possessing an A~I group~and a hydrophobic moiety. Using the model ascribed to Goodman above the hydrophobic moiety of Wog3/1067Ç A 2 1 1 7 2 8 4 PCT/Usg2/l0l79 89 ! ~
~ t Belitz would be in the -z (or bitter taste) region described by Goodman.
It is a plau ible aonsequence of the aboYe models that mol~cules c~pable of binding to one or more of the taste r~ceptor l'sites" as d~scribed by these researchers, and their models, and which do not allow a hy~rophobic group into the "X" (or G, sweet taste~ region or into the (-z) :
(bitter taste~ area, is likely to be tasteless (or nearly tasteless). Such a mo}ecule (a tastand as described herein ---abo~e) would be predicted to competitively bind to the -::
receptor and cause inhibition of one or more of the tastes ~:.
(sweet, bitter, organic bitter) produced by such a receptor.
~ hat we have found is that if a molecule is bitter or sweet and interacts with the receptor site as describ~d by the above models and such a molecule can be transformed in such a manner as to displace the hydrophobic portion of the molecule from th~ X ~G, sweet taste) zone, ~nd in such a manner that the hydrophobic portion does not interact with the ~itter taste (-z) zone, that such a molecule will t~nd to be tasteless. ~urthermore, the transformation of the hydFophobic zone:substituent to a hydrophilic substituent, and/or the increasing or decreasing of the size of the hydrophobic substituent, and/or the increasing or decreasing of the distance between the various hydrogen bonding and hy~rophobic interaction sites, may result in a change in binding conformation and/or structure in a manner which prevents substantial interaction with the sweet taste (G or X3 zone or substantial interaction with the bitter taste (-zj zone, thus, generating a substantially tasteless molecule.
We have found that an inhibitor of sweet taste or bitter taste may interact in various ways with the receptor site. Consequentlyl depending on the nature of the interaction of a tastand with the receptor, saîd tastand may be capable of competing favorably against one class of compounds, say for instance sweeteners, and unfavorably against other classes of compounds such as bitter compounds.

WO~3/10677 rA21 I 72~T/llS92/10179 Another consequence of our finding is that a model explaining both sweet and bitter taste might include the possibility that there are saparate receptors or receptor sites for sweet and bitter taste perception. Thus, if a ~;
tastand were to interact with only one of these receptors or receptor sites it could completely eliminate one sensation without affecting the other.
It ~as also been reported and we have found that there are at least two types of bitter taste. One is organic bitter t~ste which is elicited by compounds such as caffeine and the other is the bitter taste elicited by inorgani~ molecules like potassium ion. Consequently, a tastand may compete favorable against organic bitter taste, perhaps even favorably against sweet taste as well, and unfavorably against potassium ion, depending on the sites of interaction. Conversely the tastand may compete favorably against potassium ion and unfavorably against organic bitt~r or sweet tastes.
As an example of the transformations which are capable of eliciting the;re~ponses just described, L-aspartyl-L-phenylalanine methyl ester is approximately 200 times sweeter than sucrose. L-Aspartyl-L-phenylalanine ~ethyl ester can be transformed to a bitter compound by changing the L-phenylalanine methyl ester to D-phenylalanine methyl ester (which places the phenyl ring in the -z (bitter taste) zone. L-Aspartyl-L-phenylalanine methyl ester can also be tr~nsformed to a tasteless compound by changing the methyl ester to a~carboxylic acid. L-Aspartyl-L-phenylalanine (L-aspartyl-L-phenylalanine methyl ester minus the me~hyl ester) is tasteless and has been shown to effectively block the bitter taste of potassium ion~ L-Aspartyl-L-phenylalanine has minimal effect on the sw~et taste of L-aspartyl-L-phenylalanine methyl ester but does block the sweet taste of sucrose at very high concentrations (relative to the sucrose). L-Aspartyl-L
phenylalanine has very little effect on the bitter taste of caffeine but doe~ block the off-taste associated with L-aspartyl-L~phenylalanine methyl ester. N-(p Cyanophenylcarbamoyl)-L-aspartyl-L-phenylalanine methyl WO 93/10677 CA 2 1 1 72~4 PCT/US92/10179 91 , ester as described by Tinti and Nofre is-14,000 times -~
sweeter than sucrose. When this compound is transformed into N-(p-cyanophenylcarbamoyl)-L-aspartyl-L-phenylalanine, -i.e. the super sweetener minus the methyl ester, the compound becomes essentially tasteless. This compound can -now interact with the AH, B and D, but not with the X(G), portions of the receptor site and we have found thàt this compound effectiveIy blocks the bitter taste of potassium ion and the bitter taste of caffeine while having only a very small effect on the sweet taste of sucrose. N-(p-Cyanophenylcarbamoyl)-aminomethanesulfonate which possesses a D and B site, and is essentially tasteless inhibits organic bitter taste (caffeine) and sweet taste, but not the bitter taste associated with potassium chloride.
Taurine and ~-alanine which both possess an AH, B array are both example of tastands.
Consequently, it is possible to tailor c~mpounds by transforming known sweeteners or known bitter compounds into essentially tasteless molecules capable of either blocking the sweet taste response, the organic bitter ta~te response, the inorganic bitter taste response or various combinations of each. Thus, a new and previously-unanticipated teaching of this invention is that the models of Goodman and coworkers and others can be used to predict tasteless collpounds which can be used as tastands as described herein. Such tastands are predicted to be , tasteless or nearly tasteless compounds which can be generated by transformation of a sweet or bitter compound in a manner that eliminates hydrophobic interactions in the -z or X~G) areas (as defined by Goodman or Tinti and Nofre) of the taste receptor(s). Such tastands are capable of blocking or inhibiting any one or any combination of the three tastes; sweet, organic bitter or inorganic bitter.
A molecule need only interact with one of the hydrogen bonding sites described above and have little or no hydropho~ic interaction in the X~G) zone or -z zone to be a tastand. Fre~uently molecules capable of interacting with onIy one hydrogen bonding site and having a hydrophobic moiety will po88e~8 sufficient flexibility (depending on W093/lQ677 92 C A 2 1 1 7 2 8P~/US92 1 size) to enter the -z zone and will consequently be bitter tasting. Molecules with the ability to hydrogen bond with ;~
more than one complementary site on a receptor will have a better chance of keeping hydrophobic groups out of the X(G) and -z zone, and consequently should have a high probability of being a tastand.
According to the above logic, molecules which can interact with the reciprocal AH and/or B hydrogen bonding sites on a receptor as described by Goodman (Figure 3) and whose conformation~and/or structure prevents any -hydrophobic interactions in the X (sweet taste) region and which also do not allow hydrophobic interactions in the -z (bitter taste)~zone are tastands as defined herein.
Also, according to the above logic, molecu}es which can interact with the reciprocal AH and/or B and/or D ~or secondary sites~) hya ~gen bonding sites on a receptor as described by Tinti and Nofre (Figure 1) and whose conformation and/or structure prevents any hydrophobic interactions with the G (sweet taste) region and which also do not allow`hydr~ophobic`interactions in the -z (bitter taste) zone which~is developed when the AH, B, D, G system of Tinti and Nofre is superimposed into the AH, B, X system of~Goodman ~Fig~ure 4), are tastands.
.
As used herein and the appended c}aims AH, B, D, El, E2, XH, Y, X, G,~ shapeN, and the coordinates of x, y, z are defined hereinabove.

~ : -' ~;

WC~ ~3~10~77 ~ A 2 1 1 7 2 8 4 PCr/US92/10179 ~) ~igure 1.
AH - Hydrogen Bond Donor Group E~ Hydrogen Bond Acceptor &roup G - Hydrophobic Group D - Hydrogsn Bond Ac:ceptor Group X~I Weak Hydrogen Bond Donor Group y D Weak Hydrogen Bond Acceptor Group E1 ~ Waak Hydrogen Bond ~cceptor ~rs~up E2 - Weak Hydrogen Bond Acceptor Group .... .. . _ _ _ ,...
Figur@ 2 a ~
.~

CA21 l 7284 WO 93~10677 PCI/US92/1017g ;. . ..
. ; _ , . . , , , , , . , .
~S

Figure 2b .

1~ ~, ~1 ~

Figure 2c .
'~

WO93~10677 CA 2 1 1 72~4 PCT/VS92/10179 95 ; .~ :

,, ,~
Figure 2d~
: ~Figure 2~a-d. Preferred minimum ener~y eonformations of ~A) N-(L-aspartyl3-N'-(tetra~et~yl¢yclopenta~oyl3 (R)-191-~: dia~inoethane, (B) N-(L-aspartyl)-N~-(tetramethylcyclopentanoyl) (S)~ diaminoethane, (C) L- ~
aæpar~yl-D-alanyl-~etram~thylcycl~pen~ylamide and (D~ L- .
a~partyl-L-alanyl-tetramethylcyclop~ntyl~mide.

WO93/10677 C~ 2 1 ~ 7284 96 PCT/US92/10179 , ,,, . ,,,, , , _ . ;~:

Figure 3. The Goodman model ~r the sweet taste with L-asp~rtyl-L-phenylalan~ e methyl ester sup~ri~posed. The bond, shown by the arrow, has been rotated 40 from the X-ray diffraation structure. In addition, th~ hydrogen atoms have b~ n added, with the ~tandard bond lengths and angl~s.
The ~H-B and X groups o~ the molecule are illu~trated according to the Shallenberger-Xi~r suggestions. ~:
. -` ~
: ~ .

~ ' .

- ..

W093/10677~ A 2 1 1 7 2 8 4 PCT/US92/10179 97 ~
., --- , D

~ ~:
I
. .
. '::
. , , , ", ., ".
, . `.
Figure 4. L-aspartyl-~-ph~nylalanine methyl ester in the R'~-shape" proposed by Goodman for the sweet taste receptor ~uperimposed into th~ 8-centered ~odel propo~ed by Tinti and Nofre. .
~ ~any of the ab~ve t~stands exist ~ race~ic :~
: mix~ures~), minus (-3, plus (~), or dia~tere~meric optical isomers~ It hould be understood that the present invention contemplates use of the tastands in either the rac~mate or as the individual optical isomer~. It is likely that one or the other of the optical isomers of the racemic tastands possess the greater, if not all, of the blocking or tastand activity. For example, it has been found that the ~
isomer of 2-(4-methoxyphenoxy)propionic acid possesses the majority of the activity that reduces undesirable tastes.
~he use of the most active isomer alone is advantageous in that far less tastand is needed to gain th~ desired reduction in undesirable taste(s).

WO 93J10677 C A 2 1 1 7 2 8 4 Pcr/usg2/l0l7~
.. , 98 It has further been found that tastands described above and in particular (-)-2-(4-methoxyphenoxy)propionic acid, in addition to inhibiting bitter taste also enhances the salty taste of sodium containing compounds, if employed in sufficient concentration~s. Thus, the present invention contemplates the preparation of eatables containing, for example, low sodium chloride and the tastands in an amount sufficient to enhance the salty taste of sodium chloride.
Moreover, the present invention contemplates the preparation of eatables comprised of a mixture of substances havinq an undesirable taste such as potassium chloride, magnesium chloride with sodium chloride and/or ammonium chlcride in conjunction with the tastands referred to herein in an amount that both reduces the undesirable taste(s) and enhances the salty taste of the sodium chloride. Preferred eatable admixture products of the invention comprise from slightly more than 0 up to about 300% by weiqht of substances with undesirable tastes such as, for example, potassium chloride and magnesium chloride and 0 to 50% by weight sodium chloride in combination with . .
effective concentrations of a tastand(s), typically 0.001%
to about 50% preferable 0.1% to about 5%.
Moreover, the present invention contemplates the preparation of eatables such aæ ~reads, biscuits, pancakes, .
cakes, pretzels, snack foods, baked goods etc. prepared `
using for example potassium bicarbonate or potassium carbonate in place of the sodium salt& as leavening agents `~
in conjunction with a tastand in an amount sufficient to eliminate the undesirable taste associated with potassium ion or other tastes. The tastand is typically present in an amount ranging from about 0.001% to about 50% by weight, preferably about 0.1% to about 10% by weight, of the material with the undesirable taste. The present invention also contemplates the preparation of preservatives for -eatables comprised of the potassium salts of benzoate, nitrate, nitrite, sulfate and sulfite and so on, in conjunction with~an appropriate concentration of a tastand(s) to eliminate undesirable tastes in foodstuffs.
Ideally the tastand is usually about 0.00~ to about 10%, W093/t0677 CA21 17284 PCl`/US92/10179 . . .
preferably about 0.1~ to about 5%, by weight of the material with the undesirable taste.
The present invention also contemplates the use of potassium salts of flavoring agents (such as for example glutamate~ in place of sodium salts. Consequently monopotassium glutamate and/or guanalate and/or inosinate in conjunction with~an appropriate amount of tastand to eliminate most if not all of the undesirable tastes, thus rendering monopotassium glutamate essentia}ly equivalent to monosodium glutamate. m e tastand can be present from about 0.0000001% to about 300%, preferably from about 0.1% to about 5%, by weight of the material with the undesirable taste.
The present invention also contemplates the preparation of medicaments such as aspirin, acetaminophen, ibuprofen, codeine, antibiotics, etc. in conjunction with a tastand~s) in sufficient concentration to remove or reduce .
the undesirable taste(s) of these ma~erials. The tastand is ~-usually 0.001% to about 50% by weight, preferably from ..
about 0.5% to about 5% by weight of the material with the undesirable taste. The present invention also contemplates the preparation of~eatables w~ich have inherently undesirable tastes,~such as unsweetened chocolate, in conjunction with a~ tastand in sufficient concentration to eliminate or reduce the bitterness of these products. The tasta~nd is usually~;a~out 0~.001% to about 50% by weight, preferably about 0.2%~to about 5~, by weight of the material with the undesirable taste.
~ As one skill;ed in the art would recognize, this reduction in the undèsirable taste(s) could result in a reformulation of the product now that the undesirable taste(s) is ~educed. A few specific examples of this would be:
1. The preparation of lower calorie chocolate products, .~", .
2. The preparation of lower calorie beverages, 3. The preparation of an eatable with a reduced quantity of high intensity sweeteners, or 4. The preparation of an eatable with a reduced W093/10677 CA21 17284 loo PCT/~S92/10179 quantity of low intensity sweeteners.
5. The preparation of an eatable with a reduced quantity of high intensity sweeteners.
By the use of at least one tastand in an eatable with an undesirable taste; a reformulation could be made which would result a reduction in calories and/or masking agents such as l~w intensity sweeteners, high intensity ~weeteners, spices, and/or other flavorings.
The concentration of tastand employed to reduce the undesirable taste~s) in any given instance will vary depending principally on the particular tastand selected, the particular substance or substances with the undesir~ble taste(s?, the extent of the reduction of the undesirable taste(s) desired as well as the other tastes and Clavors present in the mixture. In most instances, concentrations of about O.OOl to 300% by weight, preferably about 0.05 to 5% o~ tastand to the material with the undesirable taste are satisfactory.
As an illustrative specific example, when tL tastand is selected for use with an admixture of sodium chloride and an undesirable tasting substance such as potassium chloride and~or magnesium chloride, it will generally be necessary to employ at least 0.2% by weight up to 10% by weight of the tastand based on the weight of the salt(s) to obtain both the reduction of the undesirable taste(s) and salty taste enhancement.
~ The eatables to which the tastands of the invention can be added are wi hout limitation and include both foodstuff and eatables having essentially no food value such as pharmaceuticals, medicament~ and other eatables.
Therefore, the tastands of the present invention are effective for use with all substances which have an undesirable taste(s). Illustrative of substances with undesirable taste(s) with which the taste modifiers of the invention can be used are potassium chloride, ammonium chloride, sodium chloride, magnesium chloride, halide salts, naringin, ~affeine, urea, magnesium ~ulfate, saccharin, acetosulfames, aspirin, potassium benzoate, potassium bicarbonate, potassium carbonate, potassium W093/10677 ~ A 2 1 1 7 2 ~ 4 PCT/US92tlOt79 101 '~
nitrate, potassium nitrite, potassium sult`ate, potassium sulfite, potassium glutamate, food preservatives in their physiologically acceptable salts, ibuprofen, acetaminophen, antibiotics, codeine, cognac, unsweetened chocolate, cocoa beans, yogurt, pxeservatives, flavor enhancers, dietary supplements, gelling agents, Ph control agents, nutrients, processing aids, bodying agents, dispersing agents, stabilizers, colorings, coloring diluents, anticaki~g ~.
agents, antimicrobial agents, formulation aids, leavening agents, surface active agents, anticaking agents, nutrient supplements, alkali, acids, sequestrants, denuding agent general purpose buffers, thickeners, cooked out juice retention agents, color fixatives in meat and meat products, color fixatives in poultry and poultry products, dough conditioners, maturing agents, yeast foods, mold retardants, emulsifiers, texturizers, binders, water correctives, miscellaneous and general purpose food additives, tableting aids, lye peeling agents, washing water agents, oxidizers, antioxidants, enzymes, extenders, fungicides, cake mixes, coffee, tea, dry mixes, non-dairy creamers, ~alts, animal glue adjuvant, cheese, nuts, meat and meat products,~poultry a~d poultry product, pork and pork products, fish~and fish produ~ts, vegetable and vegetable products, fruit and fruit products, smoked ~-products such as meat, cheese fish, poultry, and vegetables, whipping agents, masticatory substances in chewing gums, dough strengthene~s, animal feed, poultry feed, fish feed, pork feed, defoaming agents, juices, liquors, substances or drinks containing alcohol, beverages including but not limited to alcoholic beverages and non-al~oholic carbonated and/or non-carbonated soft drinks, whipped toppings, bulking agents used in eatables including but not limited to starches, corn solids, polysaccharides and other polymeric carbohydrates, icings, as well as potassium-containing or metal-containing substances with undesirabl~ tastes and the like.
While the above listing is extensive it is by no means all inclusive. Clearly one skilled in the art would recognize that many if not all of the:

WV93/1~677 C A ~ 1 1 7 ~ a 4 PCT/US~2/10179 A. sodium based salts or compounds, and~or, B. sodium based salts or compounds made into their non-~odium based counterparts, and/or, C. pota.~sium based salts or compounds, and/or, D. acid~ or acids made into their corr~sponding salts (sodium and/or non sodium based compounds), and/or, E. alkalis or alkalis made into their corresponding ~-salts, and/or, substances that are approved, at any time, as eatable~ by the Food and Dru~ Administration and/or that are ~RAS as defined by the Flavor Extract Manufacturers' Association could then be made more palatable by the use of th~
taætands taught herein (h reinafter and in the appended claims referred to as "material~s)"). These materials would or could be made more palatable by the reduction or elimination of any undesirable ta~tets) associated with ~:
them. ~Generally, sodiu~ based salts are better tasting -~
than the corresponding non-sodium salts.) The use of tastands with all o~ the~e materials as well as all of their anticipa~ed uses is hereby anticipated by the teachings set forth herein.
.
: Despite the breadth of this disclosure, one skilled in the art and the~teaching taught herein shall be able to : envision other examples.
~: E~AMPLE 1.
An aqueous solution (1 L) containing 20 grams of a mixture compris~d of 95~ potassium chloxide and 5% ::
odium chloride, and~0.05 grams (-)-2-(4-methoxy~henoxy)propionic acid sodium salt, gave a sodium chloride-like taste with virtually none of the ; ~ bitterness normally associated with potassium chloride.
:~ EXAMPLE 2.
An aque~us solution (100 mL) containing 2 gram~ of potassium chloride and 0.06 grams of L-aspartyl-L~
phenylalanine monopotassium salt, gave a clean, salty taste virtually free of the bitter taste normally asssciated with potassium chloride.

WO93/10677 C Q 2 1 1 7 2 8 4 P ~/US92/10179 103 i; !: `
EXAMPLE 3.
An aqueous ~olution (1 L~ containin~ 10 grams of sodium chloride and 1 gram of (-)-2-(4-methoxyph~noxy~propionic acid sodium salt had a substantially saltier taste than a 1% solution of sodium chloride alone.
EX~MPLE 4~
An agueous solution ~1 L) containing 22.5 gra~ of potassium chloride and 0.79 grams of 3-methoxyphenyl acetic acid sodium alt gave a substantially bitter~
free salty taste~
EXAMPLE 5.
An aqueous solut}on ~1 L) containing 20 grams of potassium chloride and 0.~ grams of 2,6-dihydroxybenzoic acid potassium salt was nearly devoid of the characteristic potassium chloride bitter taste.

~XAMP~E 6. t A solid preparation containing a mixture of potassium chloride (90 grams~, sodium chloride (10 grams) and ( : )-2-(4-methoxyphenoxy)propionic acid sodium salt (0.25 grams) gave a ~clean salty sodium chloride-lîke taste.
~: EXA~PLE 7 A solid preparation containing potassium chloride (80 grams), sodium :ohloride (10 grams), magnesium chloride (10 grams) and ( -~ -2-(4-metho ~ henoxy)-propionic~:acid sodiu~ salt ~0.25 gram) ga~e a well-rounded, ~alty taste with virtually no bitterness.
X~NPLE 8. ~
The taste:of~lithium chloride was greatly improved by the addition of 1% by weight (-)-20(4-msthox~phenoxy)propionic acid sodium salt . The saltine s was substantially increased.
EXAMPLE 9.
Addition of 0.5% by weight of (-~-2-(4-methoxypheno~y)propionic acid sodium salt to monopotassium glutamate produced a flavor almost : identical to monosodium glutamateO Virtually no bikter taste was detectable.

W093/10677 P~T/US92J10179 `"~ CA211 72~4 104 EXAMPLE 10.
Addition of 6~ by weight of (-)-2-14-methoxyphenoxy)propionic acid sodium salt to aspirin gave a formulation that was slightly ~our, with almost no bitter taste or characteristic "aspirin"-like bitter aftertast~.
EXAMPLE 11.
Addition of 3% by weight of (-)-2-(4- ::
methoxyphenoxy)propionic acid ~odium salt to aspirin gave a formulation substantially lacking the bitter taste o~ aspirin. ~.
EXAMPLE 12.
A solut~on containing 100 ppm caffeins and 10 ppm by weight ~relative to caffeinP) of (-)-2-(4-methoxyphenoxy)propionic acid sodium salt was almost tasteless, and virtually all of the bitterne~s was removed.
~; EXAMPLE 13.
:~ The strong bitter taste of unsweetened chocolate was nearly eliminated by the addition of 0.25% by weight of (-)-2-(4-methoxyphenoxy)propionic acid sodium ~alt. ~:

EXAMPLE 14. .
~ Potassium benzoate containing 0.5~ by weight (-) o2- (4- -:~ ~etho~yphenoxy)propionic acid sodium salt was added to foodstuffs in place of sodium benzoate. There was no : : detectable difference in the taste of the foodstuffs.
EXA~PLE 15. :
Potassium nitrate and potassi~m nitrite containing :: 0.5% ( )-2-(4-methoxyphenoxy)propionic acid sodium salt were added to foodstuffs in place of the sodium salts. There was no detectable difference in the taste.
EXAMPLE 16.
: Po~assium bicarbonate containi~g 0.5% by weight (-)-2-~4-methoxyphenoxy)propionic acid sodium salt was used in place of baking soda for the baking of biscuits.
There was essentially no bitterness detected.

WO93/10677 CA 2 1 1 7 2 84 PCTtUS92/10179 EXAMPLE 17.
Potassium bicarbonate/carbona~e mixture containing ~.5% by weight (-)-2-(4-methoxyphenoxy)propionic acid sodium salt was used in place of baking powder for the preparation of pancakes. Essentially no bitterness was detected.
EXAMPLE 18.
When 10-20 ppm of (-)-2-(4-methoxypheno~y)propionic acid sodium ~alt was added to black coffee, the strong bitter taste of the coffee was almost completely eliminated.
EXA~PLE 19~
An aqueous solution (1 L) containing 20 grams of potassium chloride and 0.6 grams of monosodium D-glutamate had substantially less bitterness than a 2%
solution of potassium chloride.
EXAMP$E 20.
An a~ueous olution (1 L) containing 20 grams of : potassium chloride and 1.2 gra~s of monopotassium D-glutamate had virtually none of the bitterness normally associate~ with potassium chlorid~
EXAMPLE 21.
Whe~ O.2S~ by~weight of hesp~ridin methyl chalcone (relative to RCl) was add~d to a 2% solution of KCl th2 bitterness of th~ KCl was reduced.

EXAMPLE
Wh2n 0.25~ by w~i~ht (relative to th~ so~ium nitrite) f ~ 2-(4~m~tho ~ henoxy)propionic acid sodium salt ~:~ was added to 1% solution of sodium nitrite, the saltiness of the sodium nitrite was enhanced.
EXAMPTE 23 .
When 5% by weight o~ hesperidin (relative to potassium chloride3 was added to a 2% solution of potassium chloride and the mixture heated to 4 0 C the bitterne s of the XCl was almost completely eliminated.
EXAMPLE 2 4 .
When 6.696 by weight of sodium D-aspartate (relative to potassium chloride~ was added to a 296 solution of potassium chloride the bitter taste of the potassium wo 93/10677 C A 2 1 1 7 2 8 4 PCT/US92/10179 ~`~ 106 chlorid~3 was reduced and there was virtually no :~
aftertaste.
EXANPLE 25.
When 0.06 grams of phenoxyacetic acid sodium salt was added to an aqueous ~olution containing 18 grams of potassium chloride and two grams of sodium chloride, the bitter taste of the potassium chloride was substantially eliminated.
~XAMPLE 26.
When 5% by weight (relative to potassium chloride) of 2-methyl-3-nitroaniline was added to a 2~ solution of potassium chloride~the bitter taste was virtually eliminated.
EXAMPLE 27.
The bitter compon¢nt of a l~ by weight aqueous calcium :~
chloride solution (lO0 mL) was substantially eliminated by the addition of 0.2 grams of (-)-2-(4-metl1oxyphenoxy)propionic acid sodium salt.
EXRMPLE 28.~ ;
The bitter component of a 1% by weight aqueous magnesium chloride soIution (lO0 mL) was reduced by the addition of 0.2 grams of (-)-2-(4- ;
~ethoxyphenoxy)propionic acid sodium salt.
~: : EXAMPLE 29.
The bitter~component of a 2% aqueous magnesîum sulfate :~ :
solutio~ oO mL3 was greatly reduced by the addition of 0.04 grams of ~ 2-(4-methoxyphenoxy)propionic : acid: sodium sal~.

When lO0 ppm:of (-)-2-~4-methoxyphenoxy)propionic acid sodium salt was added to whiskey, the strong burning ~;~ sensation of the w~iskey was substantially reduced.
;~: :EXAMPLE 31.
::~: When lO0 ppm of ~ 2-(4-m~thoxyphenoxy)propionic acid :~ sodium salt was added to cognac, the strong burning ~: sensation of the cognac was substantially reduced.
.

EX~MPLE 32.
When lO0 ppm of (-)-2-(4-methoxyphenoxy~propionic acid sodium salt was mixed with commercially prepared ~alsa sauce there was a substantial reduction in the hotness .
of the sauce. -~
EXAMPLE 33.
When lO~ (w/w relative to the saccharin) of racemic 2~
(4-metho~yphenoxy)propionic acid sodium salt was added to a O.l~ solution of sodium saccharin r vir~ually all of the bitterness was removed. There was no aftertaste noted.
~XAMPLE 34.
When 1% (w/w, relative to the potassium nitrate3 of ~-)-2-(4-methoxyphenoxy)propionic acid sodium salt was :~
added to a 3% aqueous potas~ium nitrate solution there was almost a complete elimination of the bitterne~s of :
the potassium nitrate '.~!i .
EXAMPLE 35.
When 0.25% (~ 4-methoxyphenoxy)propionic acid sodium salt w/w~was added to lO grams La Victoria Hot Salsa t~e salsa sauce was significantly less harsh.
EXAMPLE 36.
When a solution containing 25 ppm of a mixture having : a ratio of 90 parts ~+)-2-(4-methoxyphenoxy)propionic ^:
acid sodium~salt~to lO parts [-)-2-(4-: methoxyphenoxy)propionic:acid sodium ~alt and lO0 ppm sodium saccharin there was no noticeable diminution of sweetness~of the sodium saccharin and at the same time ~`
~:~ ; there was significantly Iess a~tertaste.
: EXAMPLE 37.
-. When 0.5% b~ weight of potassium 2,4-dihydroxybenzoate (relative to potassium chloride) was added to 1%
SOlUtiOIl of potassium chloride virtually all of the ~-~: bitterness of the potassium chloride was eliminated. ~;.
: EXAMPLE 38. :
When 0.5%:by weight potassium 2,4-dihydroxybenzoate ~: (relative to~the potassium chloride~ was added to a 1%
potassium chloride solution which also contains 2%
sucrose, virtually all of the bitterness of the W093~10677 PCT/US92/10179 ~ CA2117284 108 potassium chloride was eliminated and the sucrose taste was not suhstantial...~ affected.
EX~MPLE 390 When 25 mg of potassium 2,4-dihydroxybenzoate (69 ppm relative to the total volume of the cola~ was added to a cola sweetened with saccharin, virtually all of he metallic aftertaste of the saccharin was eliminat~d. -EXAMPLE 40.
When 25 ppm of potassium 2,4-dihydroxybenzoate was added to a solution containing 100 ppm sodium saccharin there wa~ no noticeable diminution of sweetness o~ the ~accharin and at the ~ame time there wa~ significantly less aftertaste.
EXAMPL~ 41.
Addition of 5% by weight (relative to the potassium chloride) of disodium ethylenediaminetetraacetic acid (EDTA) to an aqueous solution of 2% potassium chloride : greatly reduced the bitterness of potassium chloride.
E~A~PLE 42.
he bitterness o$ a 100 mL ~olution containing 0.11 caffeine was reduced to the bitterness of a 0.08%
solution of caffeine by the addition af 100 mg potassi ~ 2,4Ddihydroxybenzoate.
E ~ PLE 43.
A taste panel consisting of six tasters unanimously prsferred ~otato chips salted ~ith 1~6% w/w pota~ium chloride/codium chloride/L-aspartyl-~-phenylalanin~
~ ; pot~ssium ~alt (90/10/3) over potato chip~ salted with ;: 1. 696 w/w pot~s i~am chloride/~odium chloride (90/10) due to substantially reduced bitterness.
EXP~PIE 44.
An aqueous 50lution containi~g l~ sodium chloride and O.005% potassium 2,4-dihydroxybenzoate was salti~r than an a~ueous solution containing only 1% sodiu7.i chloride.
EXAMPLE 45.
The bitter taste of 200 mL of freshly bre~ed Sarks brand Espresso was greatly reduced by the addition of 20 mg of potassium 2,4-dihydroxybenzoate.

W093/10677 ~ A 2 1 1 7 2 8 4 PCT/VS92/10179 10~
EXAMPLE 46. "
The bitter and sour tastes of sodium acetylsalicylate was essentially absent from an agueous su~pension comprised of sodium acetylsalicylate tO.5 gram), water (2 m~) and potassium 2,4-dihydroxybenzoate ~0.375 ~:
gram) ~
EXAMPLE 47.
The bitterness of a 2% aqueous potassium chloride solution was nearly liminated by the addition of 1%
by weigh~ (relative to the potassium chloride) of 3,4-dihydroxyphenylalanine, (DL-DOPA).
EXAMPLE 48.
A sample of refried beans (100 gm) salted with potassium chloride (0.98 gm), sodium chloride (0.42 gm) and sodium:tartrate (O.15 gm) gave a clean, salty taste, almost completely devoid of bitterness, when compared with a sample of 100 grams of refried beans salted only with p~tassium chloride (0.38 gm~ and sodium chloride (O.42 gm).
EXAMPLE 49.
~ Addition of:~5%~by weight of sodium tartrate (relative : to t~e potass~ium chloride) t9 a 2% aqueous solution of potassiu~ chloride significantly reduced the bitterness~associated wi:th potassium chloride.
E ~ PLE 50.
A sample of:~refried~beans (100 gm) salted with potassium chloride:~(0.98 gm), sodium chloride (0.42 : gm) t: a 70/30 ratio) and disodium : ethylenediaminetetraacetic acid (0.7 gm) gave a clean, salty taste, virtually devoid of bitterness when compared with a~6ample of 100 gm of refried beans salted only with potassium chloride (0.98 gm) and sodium chloride (:0.4~ gm).
EXAMPLE 51.
The add~tion of 5 mg of sodium 2,4-dihydroxybenzoate to a cup of Tetley tea (200 mL) which had been sweetened with 40 mg of sodium saccharin almost completely eliminated the bitter, metallic aftertaste of the saccharin.

W093~1067/ PCT/U~92/10179 "",~ CA21~72~4 110 EXAMPLE 52.
A solid, lyophilized salt preparation composed of 70 ~arts pvtassium chloride, 30 part~ sodium chloride and :-O.35 parts potassium 2,4-dihydroxybenzoate had a ::
~harper initial salty taste, but was otherwise virtually indistinguishable from lyophilized sodium chloride. - :~
EXAMPLE 53. :
Addition of S% by weight (relati~e to the pota~sium chlorid~) of odium (+)-lactate to a 2% aqueous solution of potassium chloride significantly reduced the bitterness associated with potassium chloride.
EXAMPLE 54.
Addition of 5% by weight (relative to the potassium chloride) of sodium ascorbate to a 2% aqueous solution of potassium chloride ~ignificantly reduced the bitterness associated with potassium chloride.
EXAMP~E 55.
Addi~ion of 1% by weight (relative to the potassium ~ chloride) of sodium p-anisate to a 2~ aqueous solution : of potassium chloride reduced the bitterness associated with potassium chloride.
EXAMP~E 56.
Addition of 7:0 mg of sodium 2,4-dihydroxybenzoate to 1 liter of~a~0.04% solution of caffeine (400 mg) reduced ~:
: : the bitternes~s a~sociat~d with ca~feine.
.
EXANPLE 57.
Addition~of 0.5% by;weight ~relative to the potassium ;~
: chloride) of~DL-methionine-methyl sulfonium chloride :~
to a 2% aqueous solution of potassium chloride reduced the bi~terne~s associated with potassium chloride.
EXAMPLE 58.
: Addition of 6 grams of maltose to 100 mL of a 2%
aqueous solution of potassium chloride reduced the bitterness of the potassium chloride.
EXAMP1E 59.
To 50 grams of mashed potatoes was added 1.2 mL of a 100 mL solution containing potassium chloride (17.3 gm~, sodium chloride (1.9 gm) and (+)-2-(4 W093/10677 C A 2 1 1 7 2 ~ 4 PCT/US92/10179 111 ~'~
methoxyphenoxy)propionic acid sodium salt (O.8 ~m).
The mashed potatoes had a clean, salty taste with almost no bitter taste associated with potassium chloride.
EXAMPLE 60.
Addition of 8 mg of xanthosine 5' monophosphate to ~Oo mL of a 2% aqueous solution of potassium chloride reduced the bitterness sf potassium chloride and enhanced the saltiness.
EXAMPLE 61.
: Addition of 5% by weight (relative to the potassium chloride) of sodium 2-hydroxyphenylacetate to a ~%
agueous solution of potassium chloride significantly reduced the bitterness associated with potassium chloride.
EXAMPLE 62.
Addition of 0.5% by weight (relative to the potassium :~ chloride) of sodium l-hydroxy-2-naphthoate to a 2%
aqueous solution~of potassium chloride significantly reduced the bitt~En~ss associated wi h potassium ~: chloride.
~; EXAMPLE 63.
Addition of 1%:by weight (relative to the potassium chloride) of~sodi~m 3-hydroxy-2-naphthoate to a 2~
aqueous ~olution of potassium chloride significantly reduced the bitterness associated with potassi~m chloride.
: ~ :EXAMPLE 64. ~
ddition of 5%~by weight (relative to the potassium ;~ chl~ride) of sodium 2,4,6-trihydroxybenzoate to a 2%
aqueous solution of potassium chloride significantly reduced the bitterness associated with potassium : chloride.
~: EXAMPLE 65.
Addition of 0.5% by weight (relative to the potassium chloride) of sodium 4-aminosalicylate to a 2% a~ueous solutioll of potassium chloride reduced the bitterness associated with potassium chloride.

Wo93J1o677 CA21 17284 PCT/U~g2/1017~ ~

ExAMpLæ 66.
Addition of 1% by weight (relative to the potassium ch~oride) of sodium anthranilate to a 2~ aqueous ~:
~olution of potassium chloride reduced the bitterness a~sociated with potassium chloride.
EXAMP~E 67.
Addition of 0~5~ by weight ~relative to the potassium chloride) of sodium aniline-2 sulfonate to a 2%
aqueous ~olution of potas-~ium chloride reduced the ~-bitterness associatsd with potassium chloride.
~XA~PLE 68.
Addition of 3.5% by weight (relative to ~he potassium chloride) of 3-methoxyphenylacetic acid to a 2.25%
agueous solution of potassium chloride, reduced the bitterness associated with potassium chloride.
EXAMPLE 69.
Addition of 0.65% by wei~ht (relative to the potassium ;~ chloride) of neodiosmin to a 2~ a~ueous solution of potassium chloride reduced the bitterness associated with potassium chlorîde.
EXAMPLE 70.
Health Valley Chicken Broth (unsalted, 200 mL) salted with potassium chloride (0~8 gm), sodium chloride (0.2 gm) and sodium (+)-2-(4-m~thoxyph~noxy)propionate (Q.03 gm) (a ~0/20/3 ratio), gave a well salted flavor virtually free of any bitter.taste.
EXAMPLE 71.
Addition of 25 mg sodium 2,4-dihydro~ybenzoate to one :~ can of C&C Diet Cola (354 mL) containing 126 mg sodium sacch~rin reduced the aftertaste associated with sodium saccharin.
EX~MPLE 72.
Addition of 6.6% by weight (relative to the potassium chloride) of sodium syringate to a 2% aqueous solution of potassium chloride reduced the bitterness associated with potassium chloride.

WO93/10677 ~ $~ 113 P~T/USg2/10~79 EX~MPLE 73.-Additior. of 0.1 gram of guanosine to a 100 mL agueous solution containing 0.1 gram of a~pirin signi~icantly reduced the bitterness associated with the aspirin.
EXAMPLE 74.
Campbell's Chicken Broth ~unsalted, 100 mL) was salted with potassium hloride (1.8 gm), sodium chloride (0.2 gm) and potassium 2,4-dihydroxybenzoate (0.01 $m) (a ratio of 90/10/0.5), gave a good, salty tasting broth essentially de~oid of bitterness.
EX~MPLE 75.
Addi~ion of 5% by weight (relative to the potassium ^~
chloride) of 3,4-dihydroxyphenylacetic acid sodium salt to a 2~ aqueous solution of potasslum chloride reduced the bitterness associated with potassium chloride. ~
EXAMPLE 76. ~ -~: The bitternes~ associated with potas~ium chloride was reduced when a 2% aqueous solution of potassium :;
chloride was saturated with uric acid.
EXAMPLE 77.
: Addition of:3.7~ by weight ~relative to the potassium chloride) of ~uanosine to a ~% aqueous solution of ~potassium chloride reduced the bitterness associated ~ ~ with potassium~chloride.
: ~: EXAMPLE 78.
The bitt2rness~associated with potassium chloride was reduced when~a 2% aqueous solution of potassium :~ chloride was saturated with uracil.
;~ EXAMPLE 79.
: The bitterness associated with potassium chloride was ~ reduced when a::2% aqueous solution of potassium :~ chloride was saturated with d-biotin. :~:
EXAMPLE 80.
: The bitterness associated with potassium chloride was reduced when a 2% agueous solution of potassium ~hloride was ~aturated with DL-dihydroorotic acid.
EXAMPLE 81~
A sample of 100 gm of unsalted refried beans salted WO93~10677 C A 2 1 1 7 2 ~ 4 PCT/US92/10t79 with potassium chloride (0.98 gm), sodium chloride (0.42 gm), potassium 2,4-dihydroxybenzoate (5~0 mg), and disodium ethylenediaminetetraacetic acid (0.7 gram, 5 mL of a 14% solution, adjusted to pH 6.8) gave ~ clean, salty taste essentially devoid of bitterness.
EXAMPLE 82u ~
The bitter taste of a 2% aqueous solution of potassium - :
chloride was reduced by the addition of 20% by weight (relati~ve to the potassium chloride) of L-threonine.
EXAMPLE 83.
The bitter taste of a 2% aqueous solution of potassium chloride was nearly eliminated by the addition of 20%
by weight (relative to the potassium chloride~ of ~: sodium malate.
EXAMPLE 84.
Hains No Salt Vegetable Soup (100 gm) salted with potassium chloride (0.9 gm), sodium chloride (0~1 gm) ~ and potassium 2,4-dihydroxybenzoate (0.005 gm) ~a : ~: ratio of 90/10/.5), gave a salty, good tasting soup basically devoid of bitterne~s.
EXA~PLE 85.
Hains No Salt Vegekable Soup (100 gm) salted with potasæium chloride (0.9 gm), sodium chloride (0.1 ~m) and sodium::2,4,6-trihydroxybenzoate (0~005 gm) (a : ratio of 9~0/10/0.5), gave a salty, good tastin~ soup practically~devoid of bitterness.
EXAMPLE 86.
Hains No Salt Vegetable Soup (100 gm) sal~ed with potassium chloride (O.9 gm), so~ium chloride (0.1 gm), ~-aspartyl-L-phenyla}anine potassium salt (O.015 gm) and potasæiu~ 2,4-dihydroxybenzoate (0.0025 gm) (a ratio of 90/10/1.5/0.25~, gave a taste essentially without bitterness. It was more salty than soup salted with potassium chloride (0.9 gm), sodium chloride ~0.1 gm~ and L-aspartyl-L-phenylalanine potassium salt (0.03 gm) (a ratio of 90/10/3t or potassi~m chloride ~: (O.9 gm~, sodium chloride tO.1 gm) and potassium 2,4 :~ dihydroxybenzoate (0.005 gm) (a ratio of 90/10/0.5).

wo93tl0677 C A 2 1 1 7 2 ~ 4 11~ PCT/US92/l0l7g EXANP~E 87.
Charles brand unsalted potato chips (100 gm) salted -~
with potassium chloride (1.6 gm) and potassiu~ 2,4~
dihydro~ybenzoate tO.008 gm3 gave a good salty taste that was essentially free of any bitt~r ~aste.
E~fPI;E 88. -Charle~ brand unsalted potato chips (100 gm) ~alted with potassium chloride (0.98 gm), ~odi~m chloride (O.42 gm) and potassium 2,4-dihydroxybenzoate (0~005 gm) ~a ratio of 70/30/0.35~ gave a good salty taste devoid of bitterne~s. These chips were essentially indistinguishable from chips salted with sodium chIoride.
EXAMPLE 89.
Charles brand unsalted potato chips (100 ~m) salted with potassium :chloride (0.67 gm~, sodium chloride ~ 0.67 gm):and potassi~m 2,4-dihydroxybenzoate (0.0034 : gm) (a ratio of 50/50/0.25) gave a good salty taste as if the ¢hips~were prepared with pure sodiu~ chloride.
EXAMPLE gO ~ ~
A sampl~:of unsalt~d r~fried beans (100 gm) salted with pota~sium chloride (O.98 gm), sodium chlorîde (0.42 gm) (a ratio of 70/30~ and sodium (~)-lactate 0.1 gm) gave;~a clean, salty tas~e l~ke that of sodium chloride. ~:
~PLE ~ 9 1 .
A sample of;unsalted refrie~ beans (IOO gm) salted ; with potass~ium chloride (1.12 gm), sodium chloride (0:.48 ~)~, potassium~2,4-dihydroxybenzoate (0.0056 gm~
~ ~ .
(a ratio of:70/39/0.35) and 0.3 gm ~odlum (+)-lactate gave a tas~e eS~entially devoid of bitterness. It was also ~ore~salty then: refried beans salted wi~h potassium chloride (1.2 gm), sodium chloride (0.4 gm) ta ratio of 70/30) and sodium (t)-lactate (0.~1 gm).
EXAMPLE 92.
A sample of~unsalted refried beans (100 gm) salted with potassium chloride (1.2 gm~, sodium chloride (0.4 gm) (a ratio of 70~30) and sodium ~?-lactate (0.3 gm) :
gave a sodium chloride like taste. It was ~lso more ~`

W093/10677 ~A ~ 2 8~ 116 PCTIUS9~/10179 salty than refried beans salted with potassium chloride (1.2 gm~, sodium chloride (0.4 gm) (a ratio of 70/30) and sodium ~+)-lactate (0.1 gm).
~XAMPLE 93.
The bitter taste of a 1000 ppm solution (100 mL~ of caffeine was s~ stantially reduced by the addition of guanosine (20 mg)~ -EXAMPLE 94.
The bitter taste of a 1000 ppm solution (100 mL~ of c~affeine was almost completely eliminated by the addition of inosine (20 mg).
E ~ PLE 95. :
An aqueous solution (100 mL~ containing potassium chloride (2.0 g) and N-(L-aspartyl)-p-aminobenzoic acid monopotassium salt (0.1 g) gave a salty taste ~ without the bitterness ~ormally associated with ;~ pot~ssium chloride.
~ EXAMPLE 96.
::: An aqueous 801ution (100 mL) containing potassium chloride (2.0 g)~and N-(L-aspartyl)-p-aminobenzoic acid monopotassIum salt (0.02 g) gave a salty taste, with a substantially decrease of bitterness from potassium chloride. ~ '.
:EXaMP~E ~7~
:A~solid preparation containing a mixture of potassium chloride (1~.8 g), sodium chloride (0.2 g) and N-(L-aspartyl)-p-aminobenzoic acid ~onopotassium salt (0.02 g) gave a clean salty sodium chloride-like taste.
EXAMPLE 98.~
:
A solid lyophilized from a aqueous solution containing potassium chloride (1.8 g), sodium chloride (0.2 g) and N-(L-aspartyl)-o-aminobenzoic acid monopotassium salt (0.1 g~ gave a clean sodium chloride-like taste with virtually none of the bitterness normally associated with potassium chloride.
~ :

: :

, WO93/10677 ~ PCT/U~92/10179 ~ 117 j<~
EXAMpLE 99 ~ !
A solid obtained from a aqueous solution containing potassium chloride (l.B g), sodium chloride (0.02 g) and N~ aspartyl)~o-aminobenzoic acid monopota~sium salt gaye a bitterness-free salty taste.
~AMPLE lOC.
When 5% by weight of potassium L-aspartyl-L-tyrosine (relative to potassium chloride3 was added to a 2%
solution of potassium chloride the bitter taste of -potassium chloride was completely eliminated.
EXAMPLE 101.
When 1% by weight of potassium L-aspartyl-L-tyrosine (relative to potassium chloride) was added to a 2%
solution of pctassium chloride the bitter taste of potassium chloride was virtually eliminated.
EXAMPLE 102.
Addition of 0.5% by weight of potassium N-(p- ~
cyanophenyl-carbamoyl)-L-aspartyl-L-phenylalanine ;
(relative to potassium chloride~ to a 2% of potassium chloride olution~ave a salty taste with free of the bitter taste.
EXAMPLE 103.
Addition of 0.1% by w~ight of potassium N-(p-cyanophenyl-carbamoyl)-L-aspartyl-L-phenylalanine (relative to;pota~sium chloride) to an aqueous solution of 2~%~potassium chloride substantially eliminated~the bitter taste of potas~ium chloride.
EXAMPLE 104.
: ~:
When 0.5% by wei:ght of potassium N-(p-nitroph~nyl-carbamo~ L-aspartyl-L-phenylalanine (relative to ~ potassium chloride) was added to a 2~ potassium - ~ chloride solution, the bitter taste of potassium chloride ~as virtually eliminated.
E~AMPLE 105.

When 0.1% by weight of potassium N-~p-nitrophenyl-~ carbamoyl)-L-aspartyl-L-phenylalanine ~relative to - potassium chloride) was added to a 2~ solution of potassium chloride, no bitterness was essentially detected .

W093/10677 `~ A 2 1 ;1 7 2 ~ 4 118 PCT/US92/10179 EXAMPLE 106.
An aqueous solution (100 mL) containing potassium ahloride (2.0 g) and potas~ium L-~-a~partyl-L-phenylalanine (0.1 g) gave a salty taste with no bitter taste associated with potassium chloride.
EXAMPTE 107.
An aqueous solution (100 mL) containing pota~sium chloride (2.0 g) and potassium L-~-aspartyl-L-phenylalanine (0.02 g) gave a salty taste with a substantial reduction of bitter taste.
EXAMPLE 108.
Addition of potassium (-)-2-(4-methoxyphenoxy) propiona~e (500 mg, 10 times relative to caffeine) to a 0.05% of caffeine (100 mL) completely eliminated the bitter taste, with a lingering sweet after taste only.
EXAMPLE 109.
Addition of potassium (-)-2-(4-methoxyphenoxy) ~:~ propionate (250 mg, 5 times re~ative to caffeine) to a : ~ 0.05% of caffeine (100 mL) significantly reduced the bitter taste of~caffeine with a~sweet after taste.
EXAMPLE 110.
:~ A solid lyophilized from a solution containing potassium chloride (1.8 g), sodium chloride (0.2 g) : and;potassium N-(p-cyanophenyl~carbamoyl)-L-aspartyl- :
L-phenylalanine ;~0.010 g) gave a sodium chloride-like taste with vi ~ ually none of the:bitterness normally ; associated~with potassium chloride.
EXAMPLE 111.
A strong bitter~taste was completely eliminated when potassium N-(p-oyanophenyl-carbamoyl)-~-aspartyl-L-phenylalanine (500 mg, 10 ~ime relative to caffeine) ~:
:: wa~ added to a 0.05% solution of caffeine tlO0 mL).
: ~, EX~MPLE 112.
: A strong bitter taste was nearly eliminated when potassium N-(p-cyanophenyl-carbamoyl)-L-aspartyl-L-phenylalanine 1250 mg, 5 times relative to caffeine) ~: was added to a 0.05% caffeine solution (100 mL).

W093/10677 CA 2 1 ~ 7284 PCT/US92/10179 119 ,~
EXAMPLE 113.
An aqueous solution (100 mL) containing caffeine (50 mg) and potassium N-(p-nitr~phenyl-carbamoyl)-L-aspartyl-L-phenylalanine (500 mg) was slightly sweet and completely devoid of the bitter taste.
EXAMPLE 114.
An aqueouæ solution (100 mL) containing caffeine (S0 mg) and potassium N-(p-nitrophenyl-carbamoyl)-L-aspartyl-L-phenylalanine ~250 mg) gave almost no bitter taste with a slightly sweet taste.
EXAMPLE llS.
When 1% by weight of potassium 2,4,6-trihydroxybenzoaèe (relative to potassium chloride) was added to a 2% solution of potassium chloride the bitterness of potassium chloride was completed -eliminated. - --EXAMPLE 116.
When 0.5%~by~weight of potassium 2,4,6-trihydroxybènzoate (relative to potassium chloride) was added to a 2% solution of potassium chloride a salty taste;~was~obtained with no bitterness associated with potassium chl~oride.
EXAMP~E~ 117.~
When~0.25S~by weight of;potassium 2,4,6-trihydro ~ enzoate (relative to potassium chloride) ;was~:added~a~potas~sium chloride solution (2%), a salty and~free~of~bitterness taste were given.
EXAMPLE 118.~
A solid lyophilized from a aqueous solution of potassium chloride (1.6 g), sodium chloride (0.4 g) and potassium 2,4,6-trihydroxybenzoate (0.01 g) gave a sodium chloride-like taste with none of the bitterness associated~with~potassium chloride.
EXAMPLE 119.~ ~
A solid lyophilized from a solution containing potassium chloride (1.6 g), sodium chloride (0.4 g~
and potassium;~2,4,6-t~ihydroxybenzoate (0.005 g) gave a salty taste~virtually free of bitter taste associated~with potassium chloride.

:: :

WO93/10677 C A 2 1 1 7 2 8 4 PCT/US92~10179 ! 120 - EXAMPLE 120.
When 5% by weight of potassium taurine (relative ~o potassium chloride) wa~ added to a 2% solution of potassium chloride the bitter taste of potassium chloride was completely eliminated.
EXAMPLE 121.
The sweetness of a 4% solution of sugar (100 mL~ was significantly reduced by th addition of N-(L-aspartyl)-o-aminobenzoic acid monopota~sium salt ~40 mg)-r ~AMpLE 12 :2 .
The sweetness was completely eliminated when N-(L-aspartyl~-o-aminobenzoic acid monopotassium salt (200 mg) was added to or 4% solution of sugar (100 mL~. .
EXAMPLE 12_.
The sweetness of a 4% solution of sugar (100 mL) was reduced to the sweetness of a 2% solution of sugar by .~.
addition o~ L-aspartyl-L-phenylalanine monopotassium , salt (1.2 g, 30% relative to sugar). i-: : :
EXAMPLE 124.
The sweetnesc; of~a 0.04% solution of Aspartame~ (100 mL) was slig~-ly~reduced and the lingeri~g taste of Aspartamee eliminated ~ addition of L-asparts~-l-L-pheny.?.alanine monopot~ssium salt (400 mg, 10 times relatSve to Aspartame ).
EXAMPLE 125.
An aqueous solution (75 mL) containing glycerol (12 grams) and taurine~(0.37 grams):wherein the burning a`ftertaste of:the glycerol is substantially decreased or eliminated.
EXA~PLE 126.
An aqueous solution (?5 mL) adjusted to a pH=6 containing glycero} (12 grams~ and L-aspartyl-L
phenylalanine ~0.62 grams) wherein the burning aftertaste of the glycerol is substantially decreased or eliminated and the mixture tasted somewhat sweeter.

WO93/10677 -CA~ 8~ PCT/US92/10179 EXAMPLE 127.
An aqueous solution (75 mL) containing glycerol (12 grams) and potassium 2,4-dihydroxybenzoate (0.12 grams) wherein the burning aftertaste of the glycerol is decreased.
EXAMPLE 128.
An aqueous solution (75 mL) containing glycerol (12 ;
grams) and ~-alanine (0.60 grams) wherein the burning aftertaste of the glycerol is decreased.
EXAMPLE 129.
The aftertaste~of L-aspartyl-L-phenylalanine methyl ~; ester (Aspartame ) used to sweetened a Diet Coke (354 mL can) was substantially eliminated by the addition of 7.5 mg of L-aspar yl-L-phenylalanine.
EXAMPLE 130.
- The aftertaste of the L-aspartyl-L-phenylalanine methyl ester ~Aspartame) used to sweetened a Diet Pepsi (354~mL~c~an) was substantially eliminated by the addition of 7.5 mg of L-aspartyl-L-phenylalanine.
EXAMPLE 131. ; ~ ~
~: The aftertaste~of the saccharin used to ~weeten C&C
Diet Cola ~(354~mL can) was substantially eliminated by the addition of~10 mg;of taurine.
EXANPLE 132.
When 5% by weight of ~-a}anine (relative to potassium chloride)~was added to a 2% solution of potassium chloride the~bitter taste of potassium chloride was completely~el~iminated.
EXAMPLE 133. ~
An aqueous~solution (100 mL) containing potassium chloride~(2.0 g) and N-(L-aspartyl)-a-amino-cycIopentanecarboxylic acid mono-potassium salt (0.1 g) eliminated~almost all of the bitterness associated with potassium chloride.

W093/10677 C A 2 1 1 7 2 8 ~ PCT/USg2/10179 EXAMPLE 134.
A solid lyophilized from an a~ueous solution containing potassium ch~oride (1.8 g), sodium chloride (O.2 g)L~nd N-(L-aspartyl)-~-amino-cyclopentanecarboxylic acid mono-potassium salt (0.1 g) gave a salty sodium chloride-like taste which was . free of bitterness associated with potassium chloride.
EXAMPLE 135.
A solid lyophilized from a solution containing potassium chloride (1.8 g), sodium chloride (0.2 g) and N-(L-aspartyl)-a-amino-cyclopentanecarboxylic acid mono-potassium ~alt (0.02 g) ~ave a clean salty tast~, virtually free of the bitterness from potassium chloride.
EX~MPLE 136.
A solid lyophilized from a solution containing potassium chloride (1.8 g), sodium chloride (0.2 g) and N-(L-aspartyl)-~-amino-cyclooctanecarboxylic acid mono-potassium ~alt ~0~1 g) gave a ~alty taste. The bitter ta te of potassium chloride was essentially ~:
~:~ eliminated.
EXAMPLE 137.
Addition of 5% ~y~weight of ~-alanine (relative to potassium:chloride) to a 2% solution of potassium ~: ~ chloride eliminated the bitter taste of potassium ~;: : chloride.
: E ~ PLE 138.
A powder ;.yophilized from an aqueous mixt~re of ~ , : potassium:chloride ~1.8 g), sodium chloride ~0.2 g) and ~-alanine :(;0,1 g) gave a clean sodium chloride-: like taste~.
EXAMPLE 139.
A powder lyophilized from a mix~ure of potassium chloride ~1.8:g), sodium chloride (0.2 g) an~
alanine (0.02 g) gave a salty taste without the bitterness normally associated with potassium chloride.
EX~PLE 140.
When 5% by weight of potassium N-~phenylcarbamoyl~-L-WO93/10677 CA 21 1 7 2~4 PCT/US92/10179 123 ~.
aspartyl-L-phenylalanine (relative to potassium chloride) was added to a 2% solution of pota sium chloride, t~e bitterness associated with potassium chloride wa~ eliminated.
EXAMPLE 141.
An aqueous ~olution (100 mL~ containing L-ornithine-~alanine dihydrochloride (0.1 g) and potassium chloride g2.0 g~ at pH 6.1 gave a salty taste without ~.
bitterness.
EXAMPLE 142.
A powder lyophilized from an aqueous solution containi~ po~assium chloride (1.8 g), sodium chloride (0.2 g) and L-ornithine-~-alanine dihydrochloride at :
pH 6.1 gave a salty taste with free of bitterness.
EXAMPLE 143. .
A powder lyophilized from an aqueous solution -~
containing potassium chloride (1.8 g), sodium chloride ':
(0.2 g) and L-ornithine-~-alanine dihydrochloride :~
(0.02 g) at;pH 6.1 ~irtually elimi~ated the bitterness -~
associated~with potassium chlorid~ and gave a salty .
~ taste.
; EXAMPLE 144. ;~
Addition of 1~ by weight of ~-aminoethyl phosphonic acvid (relative to potassium chloride) to a 2%
: potassium ~hloride solution gave a salty taste free of -~
the bitter taste~a sociated with potassium chloride.
EXAMPLE 14~.
Addition of 5S by weight of ~-aminoethyl phosphonic :~ acid ~relative to potassi~m chloride) to a 2~ solution of potassium chloride gave a sa~ty taste free o~ the bitter taste~ associated with potassium chloride.
EXAMPLE 146.
A solid lyophilized from the mixture of potassium chloride (1.8 g), sodium chloride (0.2 g) and ~-aminoethyl phosphonic acid (0.02 g) gave a clean salty taste without the bitter taste associated with potassium chloride.
EXAMPLE 147. -~
A solid made f~om a solution of potassium chloride W093/10677 C A 2 1 1 7 2 8 4 PCTtVS92/10179 ~1.8 g), sodium chloride (0.2 g) and ~-aminoethyl phosphonic acid (O.l g) was completely free of the bitterness from potassium chloride.
~XA~PLE 148.
The bitterness associated with potassium chlorid~ was complet~ly eliminated when 2-amino tere-phthalic acid potassium ~alt (O.02 g, 1% relative to the potassium ~hloride) was added to a 2% solution of potassium chloride ~lO0 mL).
EXAMPLE 149. ~ ;-The bitterness associated with potassium chloride was completely eliminated when 2-amino tere-phthalic acid potass~um salt (~0.1 g, 5% relative to the potassium :~
chloride) was:added to a 2% solution of potassium chloride (lO0 mL). ~.
EXAMPLE l50.
~;~ When taurine (0.05 g, 50% relative to Acesulfame X) was added to a 0.l% solution of Acesulfame K (lO0 mL) :: the aftertaste~associated with Aeesulfame K was L
substantially decreased.
: EXAMPLE lSl.
j::
~ When taurine~(O.lO g) was added to an aqueous solution ; j : containing~Acesulfame K ~O.lO g), the sweetness was decreased and ~the aftertaste was completely : eliminated.
~: :
: EXAMPLE 152. :~ ~
: Addition~of ~-alanine (O.Ol g, 10% relative to : Acesulfame K:) :i~ a 0.1% solution of Acesulfame K (lO0 mL) fully eliminated:the off-taste associated with AcesuIfa~e:K and gave a clean sweet taste.
, EXP~lPLE }53.
Addition of ~-alanine ~0.05 g, 50% relative to Acesu1fame K):in a 0.1% solution of Acesulfame K fully :
~; eliminated the aftertaste of Acesulfame K and decreased the sweet potency by about 70%.

~:

; 125 EXAMPLE 15~.
When ~-alanine (0.025 g) was added to a can of Shasta diet cola (354 mL), the off-taste asso~iated with sodium ~accharin a~d/or Aspartame was ~ubstantially decreased.
EX~MPLE 155.
When ~-alanine (O.02 g) was added to a can of VONS
sugar-free cola (355 mL) containing sodium saccharin (C,107 g),: the aftertaste associated with saccharin wa- cmpletely eliminated.
EXANPLE 156~
Ad~ ion of ~-alanine (0O02 g) to a can of aiet Pepsi (355 mL) reduced significantly the aftertaste : associated with Aspar;~me.
: EXAMPLE 157~ ;
Addition of 50% by weight of potassium L-aspartyl-L-~: phenylalanine (relative t ~cesulfame K) to a 0.1%
solution of Acesulfame K r uced both the sweetness and aftertaste associated with Acesulfame K.
E~AMP~E 158.
`~ When 5% by weight of L-aspartyl-L-aspartic acid was added ~relative~to KCl) to a 2% solution of KCl adjusted to a p~=6, the bitterness of the KCl was virtually eliminated.

~:

.

: ~ .

Claims (315)

IT IS CLAIMED:

1. A composition comprising an eatable having an undesirable taste and at least one tastand in an amount sufficient to reduce said undesirable taste.

2. A composition comprising an eatable according to claim 1 or claim 145 wherein the material ingested is a substance having a bitter taste.

3. A composition comprising an eatable according to claim 2 wherein the tastand is a substantially tasteless sweetness inhibitor.

4. A composition comprising an eatable according to claim 2 wherein the substance is potassium chloride.

5. A composition comprising an eatable according to claim 1 or claim 145 wherein the amount of each of the tastands is about 0.0000001 to about 300% by weight.

6. A composition comprising an eatable comprising sodium chloride and a salt taste enhancing amount of at least one tastand.

7. A method of reducing undesirable taste in an eatable possessing an undesirable taste characteristic which method comprises incorporating in said eatable at least one tastand in an amount sufficient to reduce said undesirable taste.
8. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

A-1 wherein m represents 0 or 1, n represents 0, 1, 2 or 3, p represents 1, 2, 3, 4 or 5, q represents 0 or 1;
R represents H or a lower alkyl (e.g. of C1-C3 alkyl);
the substituents R', which may be the same or different, are each represented by one of the substituents of Group 1, in any combination. X+
represents H+ or a physiologically acceptable cation, and physiologically acceptable salts of any or all of the foregoing.
9. A composition comprising an eatable according to

claim 8 wherein the tastand is selected from the group consisting of:
1. (-)-2-(4-methoxyphenoxy)propionic acid, 2. (?)-2-(4-methoxyphenoxy)propionic acid, 3. (+)-2-(4-methoxyphenoxy)propionic acid, 4. 4-methoxyphenoxyacetic acid, 5. 2-(4-methoxyphenyl)propionic acid, 6. 2-(4-ethoxyphenoxy)propionic acid, 7. 3-(3,4-dimethoxyphenoxy)propionic acid, 8. 3-(3,4-dimethoxyphenyl)propionic acid, 9. 3-(2,3,4-trimethoxyphenoxy)propionic acid, 10. 3-(2-methoxyphenyl)propionic acid, 11. 1,4-benzodioxan-6-acetic acid, 12. 3-(2,3,4-trimethoxyphenyl)propionic acid, 13. 3-(3,4,5-trimethoxyphenyl)propionic acid, 14. 3-(4-methoxyphenyl)propionic acid, 15. 4-(4-methoxyphenyl)butyric acid, 16. 2-methoxyphenylacetic acid, 17. 3-methoxyphenylacetic acid, 18. 4-methylphenylacetic acid, 19. 4-trifluoromethylphenylacetic acid, 20. phenylpyruvic acid, 21. 2,3-dihydroxybenzoic acid, 22. 2-hydroxy-4-aminobenzoic acid, 23. 3-hydroxy-4-aminobenzoic acid, 24. phenoxyacetic acid, 25. gallic acid, 26. 2,4-dihydroxybenzoic acid, 27. 2,4-dihydroxyphenylacetic acid, 28. 2-(2,4-dihydroxyphenyl)propionic acid, 29. 2-(2,4-dihydroxyphenoxy'propionic acid, 30. 2-(2,4-dihydroxyphenoxy acetic acid, and the physiologically acceptable salts of any and/or all of the foregoing.
10. A method according to claim 7 or claim 146 wherein the tastand has the structure:

A-1 wherein m represents 0 or 1, n represents 0, 1, 2 or 3, p represents 1, 2, 3, 4 or 5, q represents 0 or 1;
R represents H or a lower alkyl (e.g. of C1-C3 alkyl);
the substituents R', which may be the same or different, are each represented by one of the substituents of Group 1, in any combination. X+
represents H+ or a physiologically acceptable cation, and physiologically acceptable salts of any and/or all of the foregoing.
11. A method according to claim 10 wherein the tastand is selected from the group consisting of:
1. (-)-2-(4-methoxyphenoxy)propionic acid, 2. (?)-2-(4-methoxyphenoxy)propionic acid, 3. (+)-2-(4-methoxyphenoxy)propionic acid, 4. 4-methoxyphenoxyacetic acid, 5. 2-(4-methoxyphenyl)propionic acid, 6. 2-(4-ethoxyphenoxy)propionic acid, 7. 3-(3,4-dimethoxyphenoxy)propionic acid, 8. 3-(3,4-dimethoxyphenyl)propionic acid,

9. 3-(2,3,4-trimethoxyphenoxy)propionic acid,

10. 3-(2-methoxyphenyl)propionic acid,

11. 1,4-benzodioxan-6-acetic acid, 12. 3-(2,3,4-trimethoxyphenyl)propionic acid, 13. 3-(3,4,5-trimethoxyphenyl)propionic acid, 14. 3-(4-methoxyphenyl)propionic acid, 15. 4-(4-methoxyphenyl)butyric acid, 16. 2-methoxyphenylacetic acid, 17. 3-methoxyphenylacetic acid, 18. 4-methylphenylacetic acid, 19. 4-trifluoromethylphenylacetic acid, 20. phenylpyruvic acid, 21. 2,3-dihydroxybenzoic acid, 22. 2-hydroxy-4-aminobenzoic acid, 23. 3-hydroxy-4-aminobenzoic acid, 24. phenoxyacetic acid, 25. gallic acid, 26. 2,4-dihydroxybenzoic acid, 27. 2,4-dihydroxyphenylacetic acid, 28. 2,(2,4-dihydroxyphenyl)propionic acid, 29. 2-(2,4-dihydroxyphenoxy)propionic acid, 30. 2-(2,4 dihydroxyphenoxy)acetic acid, and the physiologically acceptable salts of any and/or all of the foregoing.
12. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

B-1 wherein R7 may be selected from the group consisting of hydrogen and C1-C3 alkyl, R8 may be selected from the group consisting of hydrogen and C1-C3 alkyl and wherein R1, is the group, (as used herein and the appended claims the structure shall be referred to as B-2):

B-2 wherein R2, R3, R4, R5 and R6 are independently selected from the substituents of Group 1, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.
13. A composition comprising an eatable according to

claim 12 wherein the tastand is selected from the group consisting of:
1. 3-(3',4'dimethylbenzoyl)propionic acid, 2. 3-(2',4'-dimethylbenzoyl)propionic acid, 3. 3-(2',methyl-4'-ethylbenzoyl)propionic acid, 4. 3-(2',4',6'-trimethylbenzoyl)propionic acid, 5. 3-(4'-carboxybenzoyl)propionic acid, 6. 3-(4',-hydroxybenzoyl)propionic acid, 7. 3-(3'-methyl-4'-hydroxybenzoyl)propionic acid, 8. 3-(2',4'-dihydroxybenozoyl)propionic acid, 9. 3-(2',4'-dihydroxy-6'-methylbenzoyl)propionic acid, 10. 3-(3'-methyl-4'-ethoxybenzoyl)propionic acid, 11. 3-(3'-ethyl-4'-ethoxybenzoyl)propionic acid, 12. 3-(4'-methoxybenzoyl)propionic acid, 13. 3'-(4'-ethoxybenzoyl)propionic acid, 14. 3-(3',4'-dimethoxybenzoyl)propionic acid 15. 3-(4'-methoxybenzoyl)propionic acid 16. 3-(4'-methoxybenzoyl)-2-methylpropionic acid 17. 3-(4'-methoxybenzoyl)-3-methylpropionic acid, 18. 3',4'-dimethoxybenzoyl-2,3-dimethylpropionic acid, and physiologically acceptable salts of any and/or a?l of the foregoing.
14. A method according to claim 7 or claim 146 wherein the tastand has the structure:

B-1 wherein R7 may be selected from the group consisting of hydrogen and C1-C3 alkyl, R8 may be selected from the group consisting of hydrogen and C1-C3 alkyl and wherein R1, is the group, (as used herein and the appended claims the structure shall be referred to as B-2) B-2 wherein R2, R3, R4, R5 and R6 are independently selected from the substituents of Group 1, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.
15. A method according to claim 14 wherein the tastand is selected from the group consisting of:
1. 3-(3'-4'dimethylbenzoyl)propionic acid, 2. 3-(2',?'-dimethylbenzoyl)propionic acid, 3. 3-(2'-methyl-4'-ethylbenzoyl)propionic acid, 4. 3-(2',4',6'-trimethylbenzoyl)propionic acid, 5. 3-(4'-carboxybenzoyl)propionic acid, 6. 3-(4'-hydroxybenzoyl)propionic acid, 7. 3-(3'-methyl-4'-hydroxybenzoyl)propionic acid, 8. 3-(2',4'-dihydroxybenozoyl)propionic acid, 9. 3-(2',4'-dihydroxy-6'-methylbenzoyl)propionic acid, 10. 3-(3'-methyl-4'-ethoxybenzoyl)propionic acid, 11. 3-(3'-ethyl-4'-ethoxybenzoyl)propionic acid, 12. 3-(4'-methoxybenzoyl)propionic acid,

13. 3'-(4'-ethoxybenzoyl)propionic acid,

14. 3-(3',4'-dimethoxybenzoyl)propionic acid

15. 3-(4'-methoxybenzoyl)propionic acid 16. 3-(4'-methoxybenzoyl)-2-methylpropionic acid 17. 3-(4'-methoxybenzoyl)-3-methylpropionic acid, 18. 3',4'-dimethoxybenzoyl-2,3-dimethylpropionic acid, and physiologically acceptable salts of any and/or all of the foregoing.

16. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

C-1 wherein R1, R2, R3, R4, R5 and R6 are individually represented by one of the substituents of Group 1, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

17. A composition comprising an eatable according to claim 16 wherein the tastand is selected from the group consisting of:
1. R2=R3=R5=R6=H, R1=OC2H5, R4=NH-CO-NH2, 2. R1=OCH2CH2CH3, R2=NO2, R4=NH2, R3=R5=R6=H, 3. R1=CH3, R2=NH2, R6=NO2, R3=R4=R5=H, 4. R1=CH3, R2=NO2, R4=NH2, R3=R5=R6=H
5. 3,4-dihydroxybenzoic acid (protocatechuic acid), 6. 2,4-dihydroxybenzoic acid, 7. 3-hydroxy-4-methoxybenzoic acid, 8. 3,5-dihydroxybenzoic acid, 9. 2,3-dihydroxybenzoic acid, 10. 2-hydroxy-4-aminobenzoic acid, 11. 3-hydroxy-4-aminobenzoic acid, 12. 2,4,6-trihydroxybenzoic acid, 13. 2,6-dihydroxybenzoic acid, 14. 2-amino tere-phthalic acid and physiologically acceptable salts of any and/or all of the foregoing.

18. A method according to claim 7 or claim 146 wherein the tastand has the structure:

C-1 wherein R1, R2, R3, R4, R5 and R6 are indi???ually represented by one of ?e substituents of Group 1, in any combination, and physiologically accepte? salts of any and/or all of the foregoing.

19. A method according to claim 18 wh???in the tastand is selected from fo???wing wherein:
1. R2=R3=? ?6=H, R1=OC2H? R4=NH-? NH2, ?1=OC? CH3, R2=NO2, NH2, R 5=R6=?, 1=CH3 =NH2, R6=NO2, =R4=R5=H?
? ?1=CH3 ?NO2, R4=NH2, =R5=R6=
3,4-d????roxybenzoic acid (protocatechuic acid), 6. 2,4-dihydroxybenzoic acid, 7. 3-hydroxy-4-methoxybenzoic acid, 8. 3,5-dihydroxybenzoic acid, 9. 2,3-dihydroxybenzoic acid, 10. 2-hydroxy-4-aminobenzoic acid, 11. 3-hydroxy-4-aminobenzoic acid, 12. 2,4,6-trihydroxybenzoic acid, 13. 2,6-dihydroxybenzoic acid, 14. 2-amino tere-phthalic acid and physiologically acceptable salts of any and/or all of the foregoing.

20. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

D-1 wherein n and k independently may be 0, 1 or 2; Y
(which may be the same or different) may be N
(nitrogen), O (oxygen), or S (sulfur); Q may be represented by one of the substituents of Group 3; p and q are 1 when Y is O and p and q may be independently 1 or 2 when Y is S and p and q may be independently 2 or 3 when Y is N; R (which may be the same or different when p>1) and R' (which may be the same or different when q>1) are represented by one of the substituents of Group 2 or one of the following three structures (as used herein and the appended claims the structures shall be referred to as D-2) in any combination and the appropriate stereochemistry:

wherein Z and Z' are the same or different and are represented by OH, -O-X+, OR", NH2, NHR", N(R")2,; R"

may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R"' may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain (e.g. one of the 20 common amino acids), X+ may be H+ or a physiologically acceptable cation, preferably an alka?i metal, alkaline earth metal or ammonium cation, and physiol?gically accepted salts of any and/or all of the foregoing.

21. A composition comprising an eatable according to c1aim 20 wherein the tastand is selected from the group consisting of:
1. L-aspartyl-L-phenylalanine, 2. aminomalonyl-L-phenylalanine, 3. L-aspartyl-D-alanine, 4. L-?spartyl-D-serine, 5. L-glutamyl-L-phenylalanine, 6. N-(L-aspartyl)-p-aminobenzoic acid, 7. N-(L-aspartyl)-o-aminobenzoic acid, 8. L-aspartyl-L-tyrosine, 9. N-(p-cyanophenylcarbamoyl)-L-aspartyl-L-phenylalanine, 10. N-(p-nitrophenylcarbamoyl)-L-aspartyl-L-phenylalanine, 11. L-.beta.-aspartyl-L-phenylalanine methyl ester, 12. L-aspartyl-p-hydroxyanilide, 13. L-.beta.-aspartyl-L-phenylalanine, 14. L-aspartyl-L-serine methyl ester, 15. L-aspartyl-D-tyrosine methyl ester, 16. L-aspartyl-L-threonine methyl ester, 17. L-aspartyl-L-aspartic acid, and physiologically acceptable salts of any and/or all of the foregoing.

22. A method according to claim 7 or claim 146 wherein the tastand has the structure:

D-1 wherein n and k independently may be 0, 1 or 2; Y
(which may be the same or different) may be N
(nitrogen), O (oxygen), or S (sulfur); Q may be represented by one of the substituents of Group 3; p and q are 1 when Y is O and p and q may be independently 1 or 2 when Y is S and p and q may be independently 2 or 3 when Y is N; R (which may be the same or different when p>1) and R' (which may be the same or different when q>1) are represented by one of the substituents of Group 2 or one of the following three structures (as used herein and the appended claims the structures shall be referred to as D-2) in any combination and the appropriate stereochemistry:
wherein Z and Z' are the same or different and are represented by OH, -O-X+, OR', NH2, NHR", N(R")2'; R"
may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R"' may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain (e.g. one of the 20 common amino acids), X+ may be H+ or a physiologically acceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cation, and physiologically accepted salts of any and/or all of the foregoing.

23. A method according to claim 22 wherein the tastand is selected from the group consisting of:
1. L-aspartyl-L-phenylalanine, 2. aminomalonyl-L-phenylalanine, 3. L-aspartyl-D-alanine, 4. L-aspartyl-D-serine, 5. L-glutamyl-L-phenylalanine, 6. N-(L-aspartyl)-p-aminobenzoic acid, 7. N-(L-aspartyl)-o-aminobenzoic acid, 8. L-aspartyl-L-tyrosine, 9. N-(p-cyanophenylcarbamoyl)-L-aspartyl-L-phenylalanine, 10. N-(p-nitrophenylcarbamoyl)-L-aspartyl-L-phenylalanine, 11. L-.beta.-aspartyl-L-phenylalanine methyl ester, 12. L-aspartyl-p-hydroxyanilide, 13. L-.beta.-aspartyl-L-phenylalanine 14. L-aspartyl-L-serine methyl ester 15. L-aspartyl-D-tyrosine methyl ester 16. L-aspartyl-L-threonine methyl ester 17. L-aspartyl-L-aspartic acid and physiologically acceptable salts of any and/or all of the foregoing.

24. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

E-1 wherein R', R", R"', R6Y are each independently represented by one of the substituents of Group 2, in any combination; R4's and R5's which may be the same or different are each independently represented by one of the substituents of Group 3; n may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; Z may be C, S, P or B, q is an integer from 2 to 3 and r is an integer from 1 to 3, when Z is C, q is 2; when Z is S, P or B, q may be 2 or 3; when Z is C or S, r is 1; when Z is P or B, r is 2, and physiologically acceptable salts of any and/or all of the foregoing.

25. A composition comprising an eatable according to claim 24 wherein the tastand is selected from the group consisting of:
1. R"=CH3, R"'=4-cyanophenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 2. R"=CH3, R"'=4-nitrophenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 3. R"=CH3, R"'=4-methoxyphenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 4. R"=CH3, R"'=phenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 5. R"=H, R"'=4-cyanophenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 6. R"=H, R"'=4-nitrophenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 7. R"=H, R"'=4-methoxyphenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 8. R"=H, R"' =phenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 9. R"=CH3, R"'=4-cyanophenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 10. R"=CH3, R"'=4-nitrophenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 11. R"=CH3, R"'=4-methoxyphenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 12. R"=CH3, R"'=phenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 13. R"=H, R"'=4-cyanophenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 14. R"=H, R"'=4-nitrophenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 15. R"=H, R"'=4-methoxyphenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 16. R"=H, R"' =phenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, and physiologically acceptable salts of any and/or all of the foregoing.

26. A method according to claim 7 or claim 146 wherein the tastand has the structure:

E-1 wherein R', R", R"', R6 are each independently represented by one of the substituents of Group 2, in any combination; R4's and R5's which may be the same or different are each independently represented by one of the substituents of Group 3; n may 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; Z may be C, S, P or B, q is an integer from 2 to 3 and r is an integer from 1 to 3, when Z is C, q is 2; when Z is S, P or B, q may be 2 or 3; when Z is C or S, r is 1; when Z is P or B, r is 2, and physiologically acceptable salts of any and?or all of the foregoing.

27. A method according to claim 26 wherein the tastand is selected from the following; wherein:
1. R"=CH3, R"'=4-cyanophenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 2. R"=CH3, R"'=4-nitrophenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 3. R"=CH3, R"'=4-methoxyphenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 4. R"=CH3, R"'=phenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 5. R"=H, R"'=4-cyanophenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 6. R"=H, R"'=4-nitrophenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 7. R"=H, R"'=4-methoxyphenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 8. R"=H, R"' =phenyl, R'=R4=R5=H, n=1, Z=C, q=2, r=1, 9. R"=CH3, R"'=4-cyanophenyl, R'=R4=R5=H, n=1; Z=S, q=3, r=1, 10. R"=CH3, R"'=4-nitrophenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 11. R"=CH3, R"'=4-methoxyphenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 12. R"=CH3, R"'=phenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 13. R"=H, R"'=4-cyanophenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 14. R"=H, R"'=4-nitrophenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 15. R"=H, R"'=4 methoxyphenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, 16. R"=H, R"' =phenyl, R'=R4=R5=H, n=1, Z=S, q=3, r=1, and physiologically acceptable salts of any and/or all of the foregoing.

28. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

F-1 wherein n may be 0, 1 or 2; Y (which may be the same or different may be N (nitrogen), O (oxygen), or S
(sulfur); Q may be represented by one of the substituents of Group 3; p and q are 1 when Y is O and p and q may be independently 1 or 2 when Y is S and p and q may be independently 2 or 3 when Y is N; R
(which may be the same or different when p>1) and R' (which may be the same or different when q>1) are represented by one of the substituents of Group 2 or one of the following three structures (as used herein and the appended claims the structures shall be referred to as F-2) in any combination and the appropriate stereochemistry:

wherein Z and Z' are the same or different and are represented by OH, -O-X+, OR", NH2, NHR", N(R")2'; R" is alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R"' is alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain (e.g. one of the 20 common amino acids). X+may be H+ or a physiologically acceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cation, and physiologically acceptable salts of any and/or all of the foregoing.

29. A composition comprising an eatable according to claim 28 wherein the tastand is selected from the group consisting of:
l. L-methionyl-L-phenylalanine methyl ester, 2. L-leucyl-L-phenylalanine methyl ester, 3. L-seryl-L-phenylalanine methyl ester, 4. L-methionyl-D-alanyl-tetramethylcyclopentylamide, 5. L-seryl-D-alanyl-tetramethylcyclopentylamide, 6. L-leucyl-D-alanyl-tetramethylcyclopentylamide, 7. L-ornithyl-.beta.-alanine 8. L-diaminobutyryl-.beta.-alanine 9. L-diaminopropionyl-.beta.-alanine 10. L-lysyl-.beta.-alanine and physiologically acceptable salts of any and/or all of the foregoing.

30. A method according to claim 7 or claim 146 wherein the tastand has the structure:

wherein n may be 0, 1 or 2; Y (which may be the same or different) may be N (nitrogen), O (oxygen), or S
(sulfur); Q may be represented by one of the substituents of Group 3; p and q are 1 when Y is O and p and q may be independently 1 or 2 when Y is S and p and q may be independently 2 or 3 when Y is N; R
(which may be the same or different when p>1) and R' (which may be the same or different when q>1) are represented by one of the substituents of Group 2 or one of the following three structures (as used herein and the appended claims the structures shall be referred to as F-2) in any combination and the appropriate stereochemistry:

wherein Z and Z' are the same or different and are represented by OH, -O-X+, OR", NH2, NHR", N(R")2'; R" is alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R"' is alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain (e.g. one of the 20 common amino acids). X+may be H+ or a physiologically acceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cation, and physiologically accepted salts of any and/or all of the foregoing.

31. A method according to claim 30 wherein the tastand is selected from the group consisting of:
1. L-methionyl-L-phenylalanine methyl ester, 2. L-leucyl-L-phenylalanine methyl ester, 3. L-seryl-L-phenylalanine methyl ester, 4. L-methionyl-D-alanyl-tetramethylcyclopentylamide, 5. L-seryl-D-alanyl-tetramethylcyclopentylamide, 6. L-leucyl-D-alanyl-tetramethylcyclopentylamide, 7. L-ornithyl-.beta.-alanine 8. L-diaminobutyryl-.beta.-alanine 9. L-diaminopropionyl-.beta.-a?anine 10. L-lysyl-.beta.-alanine and physiologically acceptable salts of any and/or all of the foregoing.

32. A compo??ition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

G-1 wherein p may be 1, 2, 3, 4, or 5; the substituents R1 may each be represented by one of the substituents of Group 1, in any combination, and R2 may be represented by one of the substituents of Group 2, and physiologically acceptable salts of any and/or all of the foregoing.

33. A composition comprising an eatable according to claim 32 wherein R2=H and R1 is selected from the group consisting of:
1. 3-COOH, 2. 3-COOCH3, 3. 3-COOC2H5, 4. 3-CH3O, 5. 4-CH3O, 6. 2-Cl, 7. 3-Cl, 8. 4-Cl, 9. 4-COOC2H5, 10. 3-C6H5CH2O, 11. 4-C6H5CH2O, 12. 2-t-butyl, 13. 4-t-butyl, 14. 2-CH3, 15. 3-CH3, 16. 4-CH3, 17. 3-C2H5, 18. 4-C2H5, 19. 3,5-di CH3, and physiologically acceptable salts of any and/or all of the foregoing.

34. A method according to claim 7 or claim 146 wherein the tastand has the structure:

G-1 wherein p may be 1, 2, 3, 4, or 5; the substituents R1 may each be represented by one of the substituents of Group 1, in any combination, and R2 may be represented by one of the substituents of Group 2, and physiologioally acceptable salts of any and/or all of the foregoing.

35. A method according to claim 34 wherein R2 is H
and R1 is selected from following; wherein:
1. 3-COOH;
2. 3-COOCH3, 3. 3-COOC2H5, 4. 3-CH3O, 5. 4-CH3O, 6. 2 Cl, 7. 3-Cl, 8. 4-Cl, 9. 4-COOC2H5, 10. 3-C6H5CH2O, 11. 4-C6H5CH2O, 12. 2-t-butyl, 13. 4-t-butyl, 14. 2-CH3, 15. 3-CH3, 16. 4-CH3, 17. 3-C2H5, 18. 4-C2H5, 19. 3,5-di CH3, and physiologically acceptable salts of any and/or all of the foregoing.

36. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

wherein R1 is 5-tetrazol, p may be 1, 2, 3, or 4; and the substituents R2, which may be the same or different, may each be represented by one of the substituents of Group 1, in any combination; and R3 is represented by one of the substituents of Group 2, and physiologically acceptable salts of any and/or all of the foregoing.

37. A comp??ition comprising an eatable according to claim 36 wherein the tastand is selected from the group consisting of:
1. 1-.alpha.-5-tetrazolyl-6-chlorotryptamine, 2. 1-.alpha.-5-tetrazolyl-6-fluorotryptamine, 3. 1-.alpha.-5-tetrazolyl-6-methoxytryptamine, and physiologically acceptable salts of any and/or all of the foregoing.

38. A method according to claim 7 or claim 146 wherein the tastand has the structure:

H-1 wherein R1 is 5-tetrazol, p may be 1, 2, 3, or 4; and the substituents R2, which may be the same or different, may each be represented by one of the substituents of Group 1, in any combination; and R3 is represented by one of the substituents of Group 2, and physiologically acceptable salts of any and/or all of the foregoing.

39. A method according to claim 38 wherein the tastand is selected from the group consisting of:
1. 1-.alpha.-5-tetrazolyl-6-chlorotryptamine, 2. 1-.alpha.-5-tetrazolyl-6-fluorotryptamine, 3. 1-.alpha.-5-tetrazolyl-6-methoxytryptamine, and physiologically acceptable salts of any and/or all of the foregoing.

40. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

I-1 wherein p and q may be independently 1, 2, 3, 4, or 5;
and the substituent R1 and R2, which may be the same or different, each may be represented by one of the substituents of Group 1, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

41. A composition comprising an eatable according to claim 40 wherein the tastand is:

I-2 and physiologically acceptable salts of any and/or all of the foregoing.

42. A method according to claim 7 or claim 146 wherein the tastand has the structure:

I-1 wherein p and q may be independently 1, 2, 3, 4, or 5;
and the substituent R1 and R2, which may be the same or different, each may be represented by one of the substituents of Group 1, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

43. A method according to claim 42 wherein the tastand has the structure:

I-2 and physiologically acceptable salts of any and/or all of the foregoing.

44. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

J-1 wherein, R1 is represented by one of the substituents of Group 2, and R2 and R3, which may be the same or different, may be represented by one of the substituents of Group 3, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

45. A composition comprising an eatable according to claim 44 wherein:
1. R3=CH3, R2=H, R1=isopropyl, 2. R3=benzyl, R2=H, R1=H, 3. R1=R3=H, R2=COOH, 4. R2=R3=H, R2=p-cyanophenylcarbamoyl and physiologically acceptable salts of any and/or all of the foregoing.

46. A method according to claim 7 or claim 146 wherein the tastand has the structure:

J-1 wherein, R1 is represented by one of the substituents of Group 2, and R2 and R3, which may be the same or different, may be represented by one of the substituents of Group 3, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

47. A method according to claim 46 wherein the tastand is selected from the following wherein:

1. R3=CH3, R2=H, R1=isopropyl, 2. R3=benzyl, R2=H, R1=H, 3. R1=R3=H, R2=COOH, 4. R2=R3=H, R2=p-cyanophenylcarbamoyl and physiologically acceptable salts of any and/or all of the foregoing.

48. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

K-1 wherein p may be 1, 2, 3 or 4; the substituents R2, which may be the same or different, are each represented by one of the substituents of Group 1, in any combination, and R1 is represented by one of the substituents of Group 2, wherein R1 and R2 may be present, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

49. A composition comprising an eatable according to claim 48 wherein:
1. R1=H, R2=benzyl, p=1, 2. R1=H, R2=NO2, p=1, 3. R1=H, R2=CN, p=1, 4. R2=H, R1=cyanophenylcarbamoyl and physiologically acceptable salts of any and/or all of the foregoing.

50. A method according to claim 7 or claim 146 wherein the tastand has the structure:

K-l wherein p may be 1, 2, 3 or 4; the substituents R2, which may be the same or different, are each represented by one of the substituents of Group 1, in any combination, and R1 is represented by one of the substituents of group 2, wherein R1 and R2 may be present, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

51. A method according to claim 50 wherein the tastand is selected from the following; wherein:
1. R1=H, R2=benzyl, p=1, 2. R1=H, R2=NO2, p=1, 3. R1=H, R2=CN, p=1, 4. R2=H, R1=cyanophenylcarbamoyl and physiologically acceptable salts of any and/or all of the foregoing.

52. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

L-1 wherein R, R1 and R2, which may be the same or different, may each be represented by one of the substituents of Group 2; p may be 0 or 1; each R3 and R4 may be independently represented by one of the substituents of Group 3; n may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; Z is an element selected from the group consisting of carbon, sulfur, boron, or phosphorus; q is an integer from 2 to 3 and r is an integer from 1 to 3, when Z is C, q is 2; when Z is S, P or B, q may be 2 or 3; when Z is C or S, r is 1; when Z is P or B, r is 2; R1 or R2 can be eliminated with OH to give a cyclic amide;
and physiologically acceptable salts of any and/or all of the foregoing.

53. A composition comprising an eatable according to claim 52 wherein:
1. R1=H, R2=t-butyl, Z=S, q=3, r=1, n=0, p=0, 2. R1=H, n=O, R2=1,2,3-trimethylcyclohexyl, Z=S, q=3, r=1, 3. R1=R2=R3=R4=H, n=2, Z=S, q=3, r=l (This compound is also referred to as taurine.) 4. R1=R2=R3=R4=H, n=2, Z=C, q=2, r=l, p=0 (This compound is also referred to as .beta.-alanine.) 5. R1=p-cyanophenylcarbamoyl, R2=R3=R4=H, Z=C, q=2, r=1, n=1, p=0 6. R3=R4=R2=R1=H , n=2, Z=P , q=3, r=2, p=O
and physiologically acceptable salts of any and/or all of the foregoing.

54. A method according to claim 7 or claim 146 wherein the tastand has the structure:

L-1 wherein R, R1 and R2, which may be the same or different, may each be represented by one of the substituents of Group 2; p may be 0 or 1; each R3 and R4 may be independently represented by one of the substituents of Group 3; n may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; Z is an element selected from the group consisting of carbon, sulfur, boron, or phosphorus; q is an integer from 2 to 3 and r is an integer from l to 3, when Z is C, q is 2; when Z is S, P or B, q may be 2 or 3; when Z is C or S, r is l; when Z is P or B, r is 2; R1 or R2 can be eliminated with OH to give a cyclic amide;
and physiologically acceptable salts of any and/or all of the foregoing.

55. A method according to claim 54 wherein the tastand is selected from the following; wherein:
1. R1=H, R2=t-butyl, Z=S, q=3, r=1, n=0, p=0, 2. R1=H, n=0, R2=1,2,3-trimethylcyclohexyl, Z=S, q=3, r=1, 3. R1=R2=R3=R4=H, n=2, Z=S, q=3, r=l (This compound is also referred to as taurine.) 4. R1=R2=R3=R4=H, n=2, Z=C, g=2, r=1, p=0 (This compound is also referred to as .beta.-alanine.) 5. R1=p-cyanophenylcarbamoyl, R2=R3=R4=H, Z=C, q=2, r=1, n=1, p=0 6. R3=R4=R2=R1=H, n=2, Z=P, q=3, r=2, p=0 and physiologically acceptable salts of any and/or all of the foregoing.

56. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

M-1 wherein p may be 1, 2, 3 or 4, substituents R, R1 and R2, which may be the same or different, are each represented by one of the substituents of Group 1, in any combination and R3 is represented by one of the substituents of Group 2, wherein R, R1, R2 and R3 may be present in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

57. A composition comprising an eatable according to claim 56 wherein:
R1=R3=phenyl, R2=H, and physiologically acceptable salts of the foregoing.

58. A method according to claim 7 or claim 146 wherein the tastand has the structure:

M-1 wherein p may be 1, 2, 3 or 4, substituents R, R1 and R? which may be the same or different, are each represented by one of the substituents of Group 1, in any combination and R3 is represented by one of the substituents of Group 2, wherein R, R1, R2 and R3 may be present in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

59. A method according to claim 58 wherein the tastand is, wherein:
R1=R3=phenyl, R2=H, and physiologically acceptable salts of the foregoin?.

60. A composition comprising an eatable accord??g to claim 1 or claim 145 wherein the tastand has the structure:

N-1 wherein p may be 1, 2, 3, or 4; q may be 1, 2, 3, 4, or 5; the substituents R1 and R2, which may be the same or different are each represented by one of the substituents of Group 1, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

61. A composition comprising an eatable according to claim 60 wherein the tastand is:

N-2 and physiologically acceptable salts of any and/or all of the foregoing.

62. A method according to claim 7 or claim 146 wherein the tastand has the structure:

N-1 wherein p may be 1, 2, 3, or 4; q may be 1, 2, 3, 4, or 5; the substituents R1 and R2, which may be the same or different are each represented by one of the substituents of Group 1, in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

63. A method according to claim 62 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

64. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand is selected from amino acids and poly amino acids, and physiologically acceptable salts of any and/or all of the foregoing.

65. A composition comprising an eatable according to claim 64 wherein the tastand is selected from the group consisting of:
1. D-glutamic acid, 2. D-aspartic acid, 3. aminomalonic acid, 4. .beta.-aminoethanesulfonic acid, 5. .beta.-alanine, 6. 3,4-dihydroxyphenylalanine, 7. L-aspartyl-L-aspartic acid and physiologically acceptable salts of any and/or all of the foregoing.

66. A method according to claim 7 or claim 146 wherein the tastand is selected from:
1. amino acids 2. polyamino acids and physiologically acceptable salts of any and/or all of the foregoing.

67. A method according to claim 66 wherein the tastand is selected from the group consisting of:
1. D-glutamic acid, 2. D-aspartic acid, 3. aminomalonic acid, 4. .beta.-aminoethanesulfonic acid, 5. .beta.-alanine, 6. 3,4-dihydroxyphenylalanine, 7. L-aspartyl-L-aspartic acid and physiologically acceptable salts of any and/or all of the foregoing.

68. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand is represented by the generalized structure:

P-1 which is a representation of the following tautomers:

wherein the substituents R and R3, which may be the same or different, are each represented by one of the substituents of Group 1, in any combination; R1 and R2, which may be the same or different, may each be represented by one of the substituents of Group 2, in any combination, and A may be C, S, N, or O and when A
is C substitution on this carbon may be made with one or more of the substituents of Group 1, in any combination, when A is S or N substitution on this S
or N may be made with one of the substituents of Group 2, and physiologically acceptable salts of any and/or all of the foregoing.

69. A composition comprising an eatable according to claim 68 wherein the tastand is selected from the group consisting of:
1. Xanthosine-5'-monophospate 2. Inosine 3. Guanosine and physiologically acceptable salts of any and/or all of the foregoing.

70. A method according to claim 7 or claim 146 wherein the tastand is represented by the generalized structure:

P-1 which is a representation of the following tautomers:

wherein the substituents R and R3, which may be the same or different, are each represented by one of the substituents of Group 1, in any combination; R1 and R2, which may be the same or different, may each be represented by one of the substituents of Group 2, in any combination, and A may be C, S, N, or O and when A

is C substitution on this carbon may be made with one or more of the substituents of group 1, in any combination, when A is S or N substitution on this S
or N may be made with one of the substituents of Group 2, and physiologically acceptable salts of any and/or all of the foregoing.

71. A method according to claim 70 wherein the tastand is selected from the group consisting of:
1. Xanthosine-5'-monophospate 2. Inosine 3. Guanosine and physiologically acceptable salts of any and/or all of the foregoing.

72. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand is represented by the generalized structure:

Q-1 which is a representation of the following tautomers:

wherein R1, R2, R3, and R5, which may be the same or different, are each represented by one of the substituents of Group 1, in any combination; R4 and R6, which may be the same or different, are represented by one of the substituents of Group 2, in any combination, and A may be C, S, N, or O and when A
is C substitution on this carbon may be made with one or more of the substituents of Group 1, in any combination, when A is S or N substitution on this S
or N may be made with one of the substituents of Group 2, and physiologically acceptable salts of any and/or all of the foregoing.

73. A composition comprising an eatable according to claim 72 wherein the tastand is selected from the group consisting of:
1. orotic acid 2. dihydroorotic acids and physiologically acceptable salts of any and/or all of the foregoing.

74. A method according to claim 7 or claim 146 wherein the tastand is represented by the generalized structure:
Q-1 which is a representation of the following tautomers:
wherein R1, R2, R3, and R5, which may be the same or different, are each represented by one of the substituents of Group 1, in any combination; R4 and R6, which may be the same or different, are represent? y one of the substituents of Group 2, in any combin? on, and A may be C, S, N, or O and when A
is C substitution on this carbon may be made with one or more of the substituents of Group 1, in any combination, when A is S or N substitution on this S
or N may be made with one of the substituents of Group 2, and physiologically acceptable salts of any and/or all of the foregoing.

75. A method according to claim 74 wherein the tastand is selected from the group consisting of:
1. orotic acid 2. dihydroorotic acids and physiologically acceptable salts of any and/or all of the foregoing.

76. A composition compri ?ng an eatable according to claim 1 or claim 145 wherein the tastand is a natural product.

77. A composition comprising an eatable according to Claim 76 wherein the natural product is selected from the group consisting of:
1. alkaloids, 2. terpines, 3. monoterpines, 4. diterpines, 5. triterpines, 6. sesqueterpines, 7. flavanoides, 8. chalcones, 9. dihydrochalcones, 10. humulones, 11. lemonoids, 12. saponins, 13. coumarins, 14. isocoumarins, 15. sinapines, 16. steroids, 17. flavinones, and physiologically acceptable salts of any and/or all of the foregoing.

78. A composition comprising an eatable according to claim 76 wherein the natural product tastand is represented by one of the following general structures:
R-1 R-2 R-3 R-4 R-5 R-6 R-7 R-8 R-9 R-10 R-11 R-12 R-13 R-14 R-15 R-16 R-17 R-18 R-19 R-20 R-21 R-22 R-23 R-24 R-25 R-26 R-27 R-28 R-29 R-30 R-31 R-32 R-33 R-34 R-35 R-36

79. A composition comprising an eatable according to claim 78 wherein the tastand is selected from the group of compounds having th? struct??es:
R-37 wherein:
1. R1=.beta.-D-glc and R2=.alpha.-L-rha-3-Me, 2. R1=.beta.-D-glc2-.alpha.-L-rha, R2=H
and physiologically acceptable salts of any and/or all of the foregoing.

80. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-38 and physiologically acceptable salts of any and/or all of the foregoing.

81. A composition comprising an eatable according to claim 78 wherein the tastand is selected from the group of compounds having the structures:
R-39 and physiologically acceptable salts of any and/or all of the foregoing.

82. A composition comprising an eatable according to claim 78 wherein the tastand is selected from the group of compounds having the structures:
R-40 and physiologically acceptable salts of any and/or all of the foregoing.

83. A composition comprising an eatable according to claim 78 wherein the tastand is selected from the group of compounds having the structures:
R-41 and physiologically acceptable salts of any and/or all of the foregoing.

84. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-42 and physiologically acceptable salts of any and/or all of the foregoing.

85. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-43 and physiologically acceptable salts of any and/or all of the foregoing.

86. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-44 and physiologically acceptable salts of any and/or all of the foregoing.

87. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-45 and physiologically acceptable salts of any and/or all of the foregoing.

88. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-46 and physiologically acceptable salts of any and/or all of the foregoing.

89. A composition comprising an eatable according to claim 78 wherein the tastand is selected from the group of compounds having the structures:
R-47 and physiologically acceptable salts of any and/or all of the foregoing.

90. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-48 and physiologically acceptable salts of any and/or all of the foregoing.

91. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-49 and physiologically acceptable salts of any and/or all of the foregoing.

92. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-50 and physiologically acceptable salts of any and/or all of the foregoing.

93. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-51 and physiologically acceptable salts of any and/or all of the foregoing.

94. A composition comprising an eatable according to claim 78 wherein the tastand is selected from the group of compounds having the structures:
R-52 and physiologically acceptable salts of any and/or all of the foregoing.

95. A composition comprising an eatable according to claim 78 wherein the tastand has the structure:
R-53 and physiologically acceptable salts of any and/or all of the foregoing.

96. A composition comprising an eatable according to claim 78 wherein the tastand ? the structure:
R-54 and physiologically acceptable salts of any and/or all of the foregoing.

97. A composition comprising an eatable according to claim 78 wherein the tastand is selected from the group of compounds having the structures:
R-55 and physiologically acceptable salts of any and/or all of the foregoing.

98. A method according to claim 7 or claim 146 wherein the tastand is selected from the group consisting of tastands having the following structures:
R-1 R-2 R-3 R-4 R-5 R-6 R-7 R-8 R-9 R-10 R-11 R-12 R-13 R-14 R-15 R-16 R-17 R-18 R-19 R-20 R-21 R-22 R-23 R-26 and physiologically acceptable salts of any and/or all of the foregoing.

99. A method according to claim 98 wherein the tastand is selected from the group of compounds having the structures wherein:
1. R,=6-D-glc and R2=.alpha.-L-rha-3-Me, 2. R,=B- D-glc2-.alpha.-L-rha, R2=H
and physiologically acceptable salts of any and/or all of the foregoing.

100. A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

: 101. A method according:to claim 98 wherein the tastand is:selected from the group of compounds having the structures:

and physiologically acceptable salts of any and/or all of the foregoing.

102. A method according to claim 98 wherein the tastand is selected from the group of compounds having the structures:

and physiologically acceptable salts of any and/or all of the foregoing.

103. A method according to claim 98 wherein the tastand is selected from the group of compounds having the structures:

and physiologically acceptable salts of any and/or all of the foregoing.

104. A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

105. A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

106. A method according to claim 98 wherein the tastand has the structure:

and physiolo?cally acceptable salts of any and/or all of the foregoing.

107. A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

108. A Method according to claim 98 wherein the tastand ha the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

109. A method according to claim 98 wherein the tastand is selected from the group of compounds having the structures:

and physiologically acceptable salts of any and/or all of the foregoing.

110. A method according to alaim 98 wherein the tastalld has the stnlc:ture:

and physiologically acceptable salts of any and/or all of the foregoing .

111. A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

112, A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

113. A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

114. A method according to claim 98 wherein the tastand is selected from the group of compounds having the structures:

and physiologically acceptable salts of any and/or all of the foregoing.

115. A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

116. A method according to claim 98 wherein the tastand has the structure:

and physiologically acceptable salts of any and/or all of the foregoing.

117. A method according to claim 98 wherein the tastand is selected from the group of compounds having the structures:

and physiologically acceptable salts of any and/or all of the foregoing.

118. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

S-l wherein R1, R2, R3, and R4 which may be the same or different are each designated by one of the substituents of Group 1. R5 is represented by one of the substituents of Group 2, and R6 is represented by one of the substituents of Group 3, wherein R1, R2, R3, R4, R5, and R6, may be present in any combination, and physiologically acceptable salts of any and/or all of the foregoing,

119. A composition comprising an eatable according to claim 118 wherein the tastand is epihernandulcin.

120. A method according to claim 7 or claim 146 wherein the tastand has the structure:

wherein R1, R2, R3, and R4 which may be the same or different axe each designated by one of the substituents of Group 1. R5 is represented by one of the substituents of Group 2, and R6 is represented by one of the substituents of Group 3, wherein Rl, R2, R3, R4, R5, and R6, may be present in any combination, and physiologically acceptable salts of any and/or all of the foregoing.

121. A method according to claim 120 wherein the tastand is epihernandulcin.

122. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

wherein p may be 1, 2, 3, 4 or 5; R1, which may be the same or different, are each represented by one of the substituents of Group 1 in any combination; R2 and R3, which may be the same or different, are each represented by one of the substituents of Group 2, each R4 and R5 may be independently represented by one of the substituents of Group 3 and wherein R1, R2 R3 R4, and R5 may be present in any combination; n may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, Z may be an element selected from the group consisting of carbon, sulfur, boron, or phosphorus; q is an integer from 2 to 3 and r is an integer from 1 to 3, when Z is C, q is 2; when Z is S, P or B, Q may be 2 or 3; when Z is C or S, r is 1;
when Z is P or B, r is 2;
and physiologically acceptable salts of any and/or all of the foregoing.

123. A composition comprising an eatable according to claim 122 wherein the tastand is selected from the group consisting of:
1. R2=R3=R4=R5=H, n=2, R1=p-cyano, Z=C, q=2 r=l, p=l 2 R2=R3=R4=R5=H, n=2, R1=p-nitro, Z=C, q=2, r=l, p=l 3 R1=p-cyano; R2--R3=R4=R5=H, n=l, Z=P, q=3, r=2, p=l 4. R1=p-nitro; R2=R3=R4=R5=H, n=l, Z=P, q-3, r=2, p=1 5. R1=p-cyano: R2=R4=R5=H, n-l, Z=S, q=3, r=l, p=1 6. R1=p-nitro; R2=R3=R4=R5=H, n=l, Z=S, q=3, r=1, p=l and physiologically acceptable salts of any and/or all of thE foregoing. :

124. An method according co claim 7 or claim 146 wherein the tastand has the structure:

T-1 : wherein p may be 1, 2, 3, 4 or 5; R1, which May be the same or different,: are each represented by one of the substituents of Group 1 in any combination; R2 and R3, which may be the same or different, are each represented by one of the substituents of Group 2;
each R4 and R5 may be independently represented by one of the substituents of Group 3 and wherein R1, R2 R3 R4, and R5 may be present in any combination; n may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, l0, ll, 12, 13 14, 15, 16, 17, l8, 19, or 20; Z may be an element selected from the group consisting of carbon, sulfur, boron, or phosphorus; q is an integer from 2 to 3 and r is an integer from 1 to 3, when Z is C, q is 2; when Z is S, P or B, q may be 2 or 3; when Z is C or S, r is 1;
when Z is P or B, r is 2;
and physiologically acceptable salts of any and/or all of the foregoing.

125. A method according to claim 124 wherein the tastand is selected from the group consisting of:
1. R2=R3=R4-R5=H, n=2, Rl=p-cyano, Z=C, q=2 r=l, p=l 2. R2-R3=R4=R5-H, n=2, R1=p-nitro, Z=C, q=2, r=l, p=l 3. R1=p-cyano; R2=R3=R4=R5=H, n=l, Z=P, q=3, r=2, p=l 4. R1=p-nitro; R2=R3=R4=R5=H, n=l, Z=P, q=3, r=2, p=l 5. R1=p-cyano; R2=R3=R4=R5=H, n=l, z=S, q=3, r=l, p=l 6. R1=p-nitro; R2=R3=R4=R5=H, n=l, Z=S, q=3, r=l, p=l and physiologically acceptable salts of any and/or all of the foregoing.

126. A composition omprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

wherein A may be O(oxygen), S(sulfur), or C(carbon), and when A is C, n is 1 and when A may be O or S, n is zero; R , R , R3, R4, R5, R6, R7, R8, R9 R10 R11 and R12 which may be the same or different, and which may be present in any combination, may each be represented by one of the following: one of the substituents of "Group 1", O-R13 NH-R13, N-(Rl3)2, or S-R13, where R13 is represented by one of the substituents of "Group 2'l;
or two R substituents may be dehydrated to form an anhydride linkage; or two R substituents may form a cyclic structure, and physiologically acceptable salts of any and/or all of the foregoing.

127. A composition csmprising an eatable according to Claim 126 wherein the tastand is selected from the group consisting of:
1. 6-chloro-6-deoxytrehalose, 2. 6',6-dichloro-6',6,-dideoxytrehalose, 3. 6-ch'oro-6-deoxy-D galactose, 4. 6-chloro-6-deoxy-D-mannose, 5. 6 chloro-6-deoxy-D-mannitol, 6. methyl-2,3-di-(glycyl-glycyl)-.alpha.-D-glucopyanoside, 7. methyl-2-O-methyl-.alpha.-D-glucopyranoside, 8. methyl-3-O-methyl-.alpha.-D-glucopyranoside, 9. methyl-4-O-methyl-.alpha. -D-glucopyranoside, 10. methyl-6-O-methyl-.alpha.-D-glucopyranoside, 11. 2,2'-di-O-methyl-.alpha.,.alpha.-trehalose, 12. 3,3'-di-O-methyl-.alpha.,.alpha.-trehalose, 13. 4,4'-di-O-methyl-.alpha.,.alpha.-trehalose, 14. 6'6'-di-O-methyl.alpha.,.alpha.-trehalose, 15. 6'-O-methylsucrose, 16. 4'-O-methylsucrose, 17. 6,6'-di-O-methylsucrose, 18. 4,6'-di-O-methylsucrose, 19. 1,6'-di-O-methylsucrose, 20. cyclohexane 1,2/4,5 tetrol, 21. (+)-cyclohexane 1,3,4/2,5 pentol{(+)-proto quercitol], 22. (-) -cyclohexane 1,3,4/3,5 pentol{( )-vibo :: quercitolJ, 23. cy?hexane 1,2,3/4,5,6 hexol {neo Inositol}, 24. cyclohexane 1,2,3,5/4,6 hexol Emyo Inositol], 25. cyclohexane 1,2,4,5/3,6 hexol [muco Inositol], 26. methyl .beta.-D-arabinop?oside, 27. methyl-3-?eoxy-.alpha.-D-? ?inohexopyranoside, 28. 3-decxy-.alpha.-D-arabinohexopyranosyl-3-deoxy-.alpha.-?
arabinohexopyranose, 29. 2-deoxy-.alpha.-D-ribo-hexopyranosyl-2-deoxy-.alpha.-D-ribohexopyranose, 30. 3-deoxy-.alpha.-D-ribo hexopyranosyl-3-deoxy-.alpha.-D-ribohexopyranose, 31. 1,6-anhydro-3-dimethylamino-3-deoxy-.beta.-D-glucopyranose, 32. 1,6-anhydro-3-dimethylamino-3-deoxy-.beta.-D-altropyranose, 33. 1,6-anhydro-3-acetamido 3-deoxy-.beta.- D-glucopyranose, 34. 1,6-anhydro 3-acetamido-3-deoxy-.beta.-D-gulopyranose, 35. 1,6 -anhydro-3-amino-3-deoxy-.beta.-D-gulopyranose, 36. methyl-3,6-anhydro-.alpha.-D-glucopyranoside, 37. 3,6-anhydro-.alpha.-D-glucopyransyl-3,6-anhydro-.alpha.-D
glucopyranoside, 38. 3,6-anhydro-.alpha.-D-glucopyransyl-3,6-anhydro-.beta.-D-fructofuranoside, 39. 3,6-anhydro-.beta.-D-glucopyransyl-1,4:3,6-dianhydro .beta.-D-fructofuranoside, and physiologically acceptable salts of any and/or all of the foregoing.

128. A method according to claim 7 or claim 146 wherein the tastand has the structure:

U-l wherein A may be O(oxygen), S(sulfur), or C(carbon), and when A is C, n is 1 and when A may be O or S, n is zero; R1 R2 R3 R4 R5, R6, R7, R8, R9, R10, R11 and R12, which may be the same or different, and which may be present in any combination, may each be represented by one of the following: one of the substituents of "Group 1", O-R13, NH-Rl3, N-(R13)2, or 5-Rl3, where R13 is represented by one of the substituents of "Group 2";
or two R substituents may be dehydrated to form an anhydride linkage; or two R substituents may form a cyclic structure, and physiologically acceptable salts of any and/or all of the foregoing.

129. A method according to claim 128 wherein the tastand is selected from the group consisting of:
1. 6-chloro-6-deoxytrehalose, 2. 6',6-dichloro-6',6-dideoxytrehalose, 3. 6-chloro-6-deoxy-D-galaotose, 4. 6-chloro-6-deoxy-D-mannose, 5. 6-chloro-6-deoxy-D-mannitol, 6. methyl-2,3-di-(glycyl-glycyl)-.alpha.-D-glucopyanoside, 7. methyl-2-O-methyl-.alpha.-D-glucopyranoside, 8. meehyl-3-O-methyl-a-D-glucopyranoside, 9. methyl-4-O-methyl-.alpha.-D-glucopyranoside, 10. methyl-6-O-methyl-.alpha.-D-glucopyranoside, 11. 2,2'-di-O-methyl-.alpha.,.alpha.-trehalose, 12. 3,3'-di-O-methyl-.alpha.,.alpha.-trehalose, 13. 4,4,-di-O-methyl-.alpha.,.alpha.-trehalose, 14. 6,6'-di-O-methyl-.alpha.,.alpha.-trehalose, 15. 6'-O-methylsucrose, 16. 4'-O-methylsucrose, 17. 6,5'-di-O-methylsucrose, 18. 4,6'-di-O-methylsucrose, 19. 1,6'-di-O-methylsucrose, 20. cyclohexane 1,2/4,5 tetrol, 21. (+)-cyclohexane 1,3,4/2,5 pentol[(-)-proto quercitol], 22. (-)-cyclohexane 1,3,4/3,5 pentol[(-)-vibo quercitol], 23. cyclohexane 1,2,3/4,5,6 hexol [neo Inositol], 24. cyclohexane 1,2,3,5/4,6 hexol [myo Inositol], 25. cyclohexane 1,2,4,5/3,6 hexol [muco Inositol], 26. methyl-.beta.-D-arabinopyranoside, 27. methyl-3-deoxy-.alpha.-D-arabinohexopyranoside, 28. 3-deoxy-.alpha.-D-arabinohexopyranosyl-3-deoxy-.alpha.-D-arabinohexopyranose, 29. 2-deoxy-.alpha.-D-ribo-hexopyranosyl-2-deoxy-.alpha.-D-ribohexopyranose, 30. 3-deoxy-.alpha.-D-ribo-hexopyranosyl-3-deoxy-.alpha.-D-ribohexopyranose, 31. 1,6-anhydro-3-dimethylamino-3-deoxy-.beta.-D-glucopyranose, 32. 1,6-anhydro-3-dimethylamino-3-deoxy-.beta.-D-altropyranose, 33. 1,6-anhydro-3-acetamido-3-deoxy-.beta.-D-glucopyranose, 34. 1,6-anhydro-3-acetamido-3-deoxy-.beta.-D-gulopyranose, 35. 1,6-anhydro-3-amino-3-deoxy-.beta.-D-gulopyranose, 36. methyl-3,6-anhydro-.alpha.-D-glucopyranoside, 37. 3,6-anhydro-.alpha.-D-glucopyransyl-3,6-anhydro-.alpha.-D-glucopyranoside, 38. 3,6-anhydro-.alpha.-D-glucopyransyl-3,6-anhydro-.beta.-D-fructofuranoside, 39. 3,6-anhydro-.alpha.-D-glucopyransyl-1,4:3,6-dianhydro-.beta.-D-fructofuranoside, and physiologically acceptable salts of any and/or all of the foregoing.

130. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

wherein a, r, l, and m may be 0 or 1; n, j, and k are 0, 1, 2, or 3; each R2 and R3 which may be the same or different independently may each be represented by one of the substituents of group 3; Y (which may be the same or different) may be N (nitrogen), O (oxygen), S (sulfur); when r or m is 1 and Y is N, p or q may be 2 or 3, when r or m is 1 and Y is 0, p or q is 1; when r or m is 1 and Y is S, p may be 1 or 2; A may be H, C=O, O=S=O, S=O, O=P(H)OH, O=P(OH)2, or O=B(H OH; Q is represented by one of the substituents of Group 3; R
(which may be the same or different when p>1) and R' (which may be the same or different when q>1) are represented by one of the substituents of Group 2 or one of the following three structures as used ?erein and the appended claims the structures shall be referred to as V-2) in any combination and the appropriate stereochemistry:

wherein Y which may be the same or different may be N (nitrogen), O (oxygen), or S (s?lfur); when d is 1 and Y is N, e may be 2 or 3, when d is 1 and Y is O, e is ?; f may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; when d is 1 and Y is S, e may be 1 or 2; A may be H, C=O, O=S=O, S=O, O=P(H)OH or O=P(OH)2, O=B(H)OH; Q is represented by one of the substituents of Group 3; R"' and Q together may form a cyclic structure; any of the R3's and Q together may form a cyclic structure; any of the R3's and R?'s together may form a cyclic structure; b may be 0, 1, or 2 and c may be 0 or 1; Z
and Z' are the same or different and are represented by OH, -O-X+, OR", NH2, NHR", N(R")2,; R" may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R?
may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain (e.g. one of the 20 common amino acids), X+ may be H+ or a physiologically acceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cation, and physiologically acceptable salts of any and/or all of the foregoing.

131. A composition comprising an eatable according to claim 130 wherein the tastand is selected from the group consisting of:
1. N-(L-aspartyl)-p-aminobenzenesulfonic acid, 2. N-(aminomalonyl)-p-aminobenzenesulfonic acid, 3. amino ethane phosphoric acid, 4. N-[N-(p-cyanophenylcarbamoyl)-L-aspartyl]-p-aminobenzenesulfonic acid, 5. N(-L-aspartyl)-1-aminocyclopentane-1-carboxylic acid, 6. N(-L-aspartyl)-1-aminocyclopropane-1-carboxylic acid, 7. N(-L-aspartyl)-1-aminocyclooctane-1-carboxylic acid, 8. N(-L-aspartyl)-1-aminocyclohexane-1-carboxylic acid, 9. N(-L-aspartyl)-2-aminocyclopentane-1-carboxylic acid, and physiologically acceptable salts of any and/or all of the foregoing.

132. A method according to claim 7 or claim 14 wherein the tastand has the structure:

wherein a, r, l, and m may be 0 or 1; n, j, and k are 0, 1, 2, or 3; each R2 and R? which may be the same or different independently may each be represented by one of the substituents of group 3; Y (which may be the same or different) may be N (nitrogen), O (oxygen), or S (sulfur); when r or m is 1 and Y is N, p or q may be 2 or 3, when r or m is 1 and Y is O, p or q is 1; when r or m is 1 and Y is S, p may be 1 or 2; A may be H, C=O, O=S=O, S=O, O=P(H)OH, O=P(OH)2, or O=B(H)OH; Q is represented by one of the substituents of Group 3; R
(which may be the same or different when p>1) and R' (which may be the same or different when q>1) are represented by one of the substitutents of Group 2 or one of the following three structures (as used herein and the appended claims the structures shall be referred to as V-2) in any combination and the appropriate stereochemistry:

wherein Y (which may be the same or different) may be N (nitrogen), O (oxygen), or S (sulfur); when d is 1 and Y is N, e may be 2 or 3, when d is 1 and Y is O, e is 1; f may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; when d is 1 and Y is S, e may be 1 or 2; A may be H, C=O, O=S=O, S=O, O=P(H)OH or O=P(OH)2, O=B(H)OH; Q is represented by one of the substituents of Group 3; R"' and Q together may form a cyclic structure; any of the R3's and Q together may form a cyclic structure; any of the R3's and R"''s together may form a cyclic structure; b may be 0, 1, or 2 and c may be 0 or 1; Z
and Z' are the same or different and are represented by OH, -O-X+, OR", NH2, NHR", N(R")2,; R" may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R"' may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain (e.g. one of the 20 common amino acids), X+ may be H+ or a physiologically acceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cation, and physiologically acceptable salts of any and/or all of the foregoing.

133. A method according to claim 132 wherein the tastand is selected from the group consisting of:
1. N-(L-aspartyl)-p-aminobenzenesulfonic acid, 2. N-(aminomalonyl)-p-aminobenzenesulfonic acid, 3. amino ethane phosphoric acid, 4. N-[N-(p-cyanophenylcarbamoyl)-L-aspartyl]-p-aminobenzenesulfonic acid, ?-L-aspartyl)-1-aminocyclopentane-1-carboxylic acid, 6. ?(-L-aspartyl)-1-aminocyclopropane-1-carboxylic acid, 7. N(-L-aspartyl)-1-aminocyclooctane-1-carboxylic acid, 8. N(-L-aspartyl)-1-aminocyclohexane-1-carboxylic acid, 9. N(-L-aspartyl)-2-aminocyclopentane-1-carboxylic acid, and physiologically acceptable salts of any and/or all of the foregoing.

134. A composition comprising an eatable according to claim 1 or claim 145 wherein the tastand has the structure:

wherein r, l, and m may be 0 or 1; j, and k may be 0, 1, 2, or 3; each R2 and R3 which may be the same or different independently may each be represented by one of the substituents of group 3; Y (which may be the same or different) may be N (nitrogen), O (oxygen), or S (sulfur); when r or m is 1 and Y is N, p or q may be 2 or 3, when r or m is 1 and Y is O, p or q is 1; when r or m is 1 and Y is S, p may be 1 or 2; A may be H, C=O, O=S=O, S=O, O=P(H)OH, O=P(OH)2, or O=B(H)OH; Q is represented by one of the substituents of Group 3; R"' and Q together may form a cyclic structure; any of the R3's and Q together may form a cyclic structure; any of the R3's and R"' together may form a cyclic structure; any of the R3's and R"' together may form a cyclic structure; R (which may be the same or different when p>1) and R' (which may be the same or different when q>1) are represented by one of the substituents of Group 2 or one of the following three structures (as used herein and the appended claims the structures shall be referred to as W-2) in any combination and the appropriate stereochemistry:

wherein Y (which may be the same or different) may be N (nitrogen), O (oxygen), or S (sulfur); when d is 1 and b is 0 and Y is N, e may be 2 or 3, when d is 1 and b is 0 and Y is O, e is 1; f may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; when d is 1 and b is 0 and Y is S, e may be 1 or 2; A may be H, C=O, O=S=O, S=O, O=P(H)OH
or O=P(OH)2, O=B(H)OH; Q is represented by one of the substituents of Group 3; b may be 0, 1, or 2 and c may be 0 or 1; Z and Z' are the same or different and are represented by OH, -O-X+, OR", NH2, NHR", N(R")2,; R"
may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R"' may be a??yl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain (e.g. one of the 20 common amino acids), X+ may be H+ or a physiologically acceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cation, and physiologically acceptable salts of any and/or all of the foregoing.

135. A composition comprising an eatable according to claim 134 wherein the tastand is selected from the group consisting of:
1. L-ornithyl-taurine 2. L-ornithyl-.beta.-alanine 3. L-lysyl-taurine 4. L-diaminobutyryl-taurine 5. L-diaminobutyryl-.beta.-alanine 6. L-diaminopropionyl-.beta.-alanine 7. L-diaminopropionyl-taurine 8. L-lysyl-.beta.-alanine 9. L-methionyl-taurine 10. L-methionyl-.beta.-alanine 11. N-(L-oxnithyl-)-p-aminobenzenesulfonic acid and physiologically acceptable salts of any and/or all of the foregoing.

136. A method according to claim 7 or claim 146 wherein the tastand has the structure:

wherein r, l, and m may be 0 or 1; j, and k may be 0, 1, 2, or 3; each R2 and R3 which may be the same or different independently may each be represented by one of the substituents of group 3; Y (which may be the same or different) may be N (nitrogen), O (oxygen), or S (sulfur); when r or m is 1 and Y is N, p or q may be 2 or 3, when r or m is 1 and Y is O, p or q is 1; when r or m is 1 and Y is S, p may be 1 or 2; A may be H, C=O, O=S=O, S=O, O=P(H)OH, O=P(OH)2, or O=B(H)OH; Q is represented by one of the substituents of Group 3; R"' and Q together may form a cyclic structure; any of the R3's and Q together may form a cyclic structure; any of the R3's and R"' together may form a cyclic structure; any of the R3's and R"' together may form a cyclic structure; R (which may be the same or different when p>1) and R' (which may be the same or different when q>1) are represented by one of the substituents of Group 2 or one of the following three structures (as used herein and the appended claims the structures shall be referred to as W-2 in any combination and the appropriate stereochemistry:

wherein Y (which may be the same or different) may be N (nitrogen), O (oxygen), or S (sulfur); when d is 1 and b is 0 and Y is N, e may be 2 or 3, when d is 1 and b is 0 and Y is O, e is 1; f may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10; when d is 1 and b is 0 and Y is S, e may be 1 or 2; A may be H, C=O, O=S=O, S=O, O=P(H)OH
or O=P(OH)2 , O=B(H)OH; Q is represented by one of the substituents of Group 3; b may be 0, 1, or 2 and c may be 0 or 1; Z and Z' are the same or different and are represented by OH, -O-X+, OR", NH2, NHR", N(R")2,; R"
may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl substituted aryl, substituted aralkyl, substituted alkaryl, and R"' may be alkyl, branched alkyl, aryl, aralkyl, alkaryl, cycloalkyl, substituted alkyl, substituted cycloalkyl, substituted aryl, substituted aralkyl, substituted alkaryl, or an amino acid side chain (e.g. one of the 20 common amino acids), X+ may be H+ or a physiologically acceptable cation, preferably an alkali metal, alkaline earth metal or ammonium cation, and physiologically acceptable salts of any and/or all of the foregoing.

137. A method according to claim 136 wherein the tastand is selected from the group consisting of:
1. L-ornithyl-taurine 2. L-ornithyl-.beta.-alanine 3. L-lysyl-taurine 4. L-diaminobutyryl-taurine 5. L-diaminobutyryl-.beta.-alanine 6. L-diaminspropionyl-.beta.-alanine 7. L-diaminopropionyl-taurine 8. L-lysyl-.beta.-alanine 9. L-methionyl-taurine 10. L-methionyl-.beta.-alanine 11. N-(L-ornithyl-)-p-aminobenzenesulfonic acid and physiologically acceptable salts of any and/or all of the foregoing.

138. A composition comprising an eatable according to Claim 1 or claim 145 wherein the tastand is selected from the class of compounds commonly referred to as chelators and all their physiologically acceptable salts of any and/or all of the foregoing.

139. A composition comprising an eatable according to claim 138 wherein the chelator is selected from the group consisting of:
1. ethylenediaminetetraacetic acid, 2. tartaric acid, 3. lactic acid, 4. ascorbic acid and the physiologically acceptable salts of any and/or all of the foregoing.

140. A composition comprising an eatable according to claim 138 wherein the chelator is selected from the group consisting of:
1. 2,4-Dihydroxybenzoic acid, 2. 3,4-Dihydroxybenzoic acid, 3. .alpha.-Amino acids, 4. .alpha.-Hydroxy acids, 5. peptides, 6. sulfonamides 7. .beta.-Amino acids, and physiologically acceptable salts of any and/or all of the foregoing.

141. A composition comprising an eatable according to claim 1 or claim 145 wherein the surfactant is an amphipathic molecule and physiologically acceptable salts of any and/or all of the foregoing.

142. A composition comprising an eatable according to claim 141 wherein the surfactant is selected from the group consisting of:
1. tergitols 2. pluronics 3. poloxamars 4. quaternary ammonium salts 5. sorbitans 6. tritons 7. polyoxyethylene ethers 8. sulfonic acid salts and the physiologically acceptable salts of any and/or all of the foregoing.

143. A method according to claim 7 or claim 146 wherein at least one surfactant is used with at least one tastand to increase the effectiveness of at least one of the tastand.

144. A method according to claim 7 or claim 146 wherein at least one surfactant is used with at least one tastand to decrease the effectiveness of at least one of the tastand.

145. A method according to claim 144 wherein the tastand is selected from the group consisting of:
1. tergitols 2. pluronics 3. poloxamars 4. quaternary ammonium salts 5. sorbitans 6. tritons 7. polyoxyethylene ethers 8. sulfonic acid salts and the physiologically acceptable salts of any and/or all of the foregoing.

146. A composition comprising an eatable having an undesirable taste and at least one tastand wherein said tastand is a molecule which can interact with at least one of the hydrogen bonding sites on the taste receptor which are complementary or reciprocal to by the AH, B, D, E1, E2, XH, or Y hydrogen bonding configurations for sweet molecules and whose conformation and/or structure prevents substantial hydrophobic interactions in the X(G) zone and which also does not allow substantial hydrophobic interactions in the -Z zone.

147. A method of reducing undesirable taste in an eatable possessing an undesirable taste characteristic which method comprises incorporating in said eatable at least one tastand in an amount sufficient to reduce said undesirable taste wherein said tastand is a molecule which can interact with at least one of the hydrogen bonding sites of the taste receptor which are complementary or reciprocal to by the AH, B, D, E1, E2, XH, or Y hydrogen bonding configurations for sweet molecules and whose conformation and/or structure prevents substantial hydrophobic interactions in the X(G) zone and which also does not allow substantial hydrophobic interactions in the -Z zone.

148. A composition comprising an eatable according to claim 6 comprising a substance having bitter taste characteristics and sodium chloride or ammonium chloride and at least one tastands in an amount that both reduces bitterness of the bitter eatable and enhances the salty taste of the sodium chloride or ammonium chloride.

149. A composition comprising an eatable according to claim 147 wherein the substance having a bitter taste is potassium chloride.

150. A method according to claim 7 or claim 146 wherein the undesirable taste is a bitter taste.

151. A method according to claim 7 or claim 146 wherein the substance has both a bitter and a desirable taste characteristic.

152. A method according to claim 7 or claim 146 wherein the substance is potassium chloride.

153. A method according to claim 7 or claim 146 wherein the amount of each tastand is about 0.0000001 to about 50% by weight.

154. A composition according to claim 1 or claim 145 wherein the eatable comprises L-aspartyl-L-phenylalanine methyl ester (Aspartame?), and physiologically acceptable salts thereof.

155. A composition according to claim 1 or claim 145 wherein the eatable comprises saccharin, and physiologically acceptable salts thereof.

156. A composition according to claim 1 or claim 145 wherein the eatable comprises L-aspartyl-D-alanine-N-(2,2,4,4-tetramethyl thiatan-3-yl)amide (Alitame?), and physiologically acceptable salts thereof.

157. A composition according to claim 1 or claim 145 wherein the eatable comprises 1,6-dichloro-1,6-dideoxy-.beta.-D-fructofuranoysl-4-chloro-4-deoxy-.alpha.-D-galactopyranoside (Sucralose?), and physiologically acceptable salts thereof.

158. A composition according to claim 1 or claim 145 wherein the eatable comprises 6-methyl-1,2,3-oxathiazin-4(3H)-one 2,2-dioxide (Acesulfame?), and physiologically acceptable salts thereof.

159. A composition according to claim 1 or claim 145 wherein the eatable comprises 6-methyl-1,2,3-oxathiazin-4(3H)-one 2,2-dioxide potassium salt (Acesulfame-K?), and physiologically acceptable salts thereof.

160. A composition according to claim 1 or claim 145 wherein the eatable comprises cyclohexylsulfamic acid, and physiologically acceptable salts thereof.

161. A composition according to claim 1 or claim 145 wherein the eatable comprises N-(1-aspartyl)-N'(2,2,5,5,tetramethylcyclopentanoyl)1,1-diaminoethane, and physiologically acceptable salts thereof.

162. A composition according to claim 1 or claim 145 wherein the eatable comprises cyclohexylsulfamic acid, and physiologically acceptable salts thereof.

163. A composition according to claim 1 or claim 145 wherein the eatable comprises guanodinium class sweeteners, and physiologically acceptable salts thereof.

164. A composition according to claim 1 or claim 145 wherein the eatable comprises dihydrochalcone class sweetener, and physiologically acceptable salts thereof.

165. A composition according to claim 1 or claim 145 wherein the eatable comprises stevioside, and physiologically acceptable salts thereof.

166. A composition according to claim 1 or claim 145 wherein the eatable comprises miraculin, and physiologically acceptable salts thereof.

167. A composition according to claim 1 or claim 145 wherein the eatable comprises thaumatin, and physiologically acceptable salts thereof.

168. A composition according to claim 1 or claim 145 wherein the eatable comprises N-(p-cyanophenylcarbamoyl)-L-aspartyl-L-phenylalanine methyl ester, and physiologically acceptable salts thereof.

169. A composition according to claim 1 or claim 145 wherein the tastand is (-)-2-(4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

170. A method according to claim 7 or claim 146 wherein the tastand is (-)-2-(4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

171. A composition according to claim 1 or claim 145 wherein the tastand is (4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

172. A method according to claim 7 or claim 146 wherein the tastand is (4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

173. A composition according to claim 1 or claim 145 wherein the tastand is (?)-2-(4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

174. A method according to claim 7 or claim 146 wherein the tastand is (?)-2-(4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

175. A composition according to claim 1 or claim 145 wherein the tastand is (-)-2-(4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

176. A method according to claim 7 or claim 146 wherein the tastand is (-)-2-(4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

177. A composition according to claim 1 or claim 145 wherein the tastand is (+)-2-(4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

178. A method according to claim 7 or claim 146 wherein the tastand is (+)-2-(4-methoxyphenoxy)propionic acid, and physiologically acceptable salts thereof.

179. A composition according to claim 1 or claim 145 wherein the tastand is (+)-lactic acid, and physiologically acceptable salts thereof.

180. A method according to claim 7 or claim 146 wherein the tastand is (+)-lactic acid, and physiologically acceptable salts thereof.

181. A composition according to claim 1 or claim 145 wherein the tastand is (-)-lactic acid, and physiologically acceptable salts thereof.

182. A method according to claim 7 or claim 146 wherein the tastand is (-)-lactic acid, and physiologically acceptable salts thereof.

183. A composition according to claim 1 or claim 145 wherein the tastand is .beta.-alanine, and physiologically acceptable salts thereof.

184. A method according to claim 7 or claim 146 wherein the tastand is .beta.-alanine, and physiologically acceptable salts thereof.

185. A composition according to claim 1 or claim 145 wherein the tastand is .beta.-aminoethyl phosphonic acid, and physiologically acceptable salts thereof.

186. A method according to claim 7 or claim 146 wherein the tastand is .beta.-aminoethyl phosphonic acid, and physiologically acceptable salts thereof.

187. A composition according to claim 1 or claim 145 wherein the tastand is acetylsalicylic acid, and physiologically acceptable salts thereof.

188. A method according to claim 7 or claim 146 wherein the tastand is acetylsalicylic acid, and physiologically acceptable salts thereof.

189. A composition according to claim 1 or claim 145 wherein the tastand is aniline-2-sulfonic acid, and physiologically acceptable salts thereof.

190. A method according to claim 7 or claim 146 wherein the tastand is aniline-2-sulfonic acid, and physiologically acceptable salts thereof.

191. A composition according to claim 1 or claim 145 wherein the tastand is anthranilic acid, and physiologically acceptable salts thereof.

192. A method according to claim 7 or claim 146 wherein the tastand is anthranilic acid, and physiologically acceptable salts thereof.

193. A composition according to claim 1 or claim 145 wherein the tastand is d-biotin, and physiologically acceptable salts thereof.

194. A method according to claim 7 or claim 146 wherein the tastand is d-biotin, and physiologically acceptable salts thereof.

195. A composition according to claim 1 or claim 145 wherein the tastand is D-aspartic acid, and physiologically acceptable salts thereof.

196. A method according to claim 7 or claim 146 wherein the tastand is D-aspartic acid, and physiologically acceptable salts thereof.

197. A composition according to claim 1 or claim 145 wherein the tastand, is D-glutamic acid, and physiologically acceptable salts thereof.

198. A method according to claim 7 or claim 146 wherein the tastand is D-glutamic acid, and physiologically acceptable salts thereof.

199. A composition according to claim 1 or claim 145 wherein the tastand is ethylenediaminetetraacetic acid (EDTA), and physiologically acceptable salts thereof.

200. A method according to claim 7 or claim 146 wherein the tastand is ethylenediaminetetraacetic acid (EDTA), and physiologically acceptable salts thereof.

201. A composition according to claim 1 or claim 145 wherein the tastand is DL-3,4-dihydroxyphenylalanine, (DL-DOPA), and physiologically acceptable salts thereof.

202. A method according to claim 7 or claim 146 wherein the tastand is DL-3,4-dihydroxyphenylalanine, (DL-DOPA), and physiologically acceptable salts thereof.

203. A composition according to claim 1 or claim 145 wherein the tastand is DL-dihydroorotic acid, and physiologically acceptable salts thereof.

204. A method according to claim 7 or claim 146 wherein the tastand is DL-dihydroorotic acid, and physiologically acceptable salts thereof.

205. A composition according to claim 1 or claim 145 wherein the tastand is DL-methionine-methyl sulfonium chloride, and physiologically acceptable salts thereof.

206. A method according to claim 7 or claim 146 wherein the tastand is DL-methionine-methyl sulfonium chloride, and physiologically acceptable salts thereof.

207. A composition according to claim 1 or claim 145 wherein the tastand is guanosine, and physiologically acceptable salts thereof.

208. A method according to claim 7 or claim 146 wherein the tastand is guanosine, and physiologically acceptable salts thereof.

209. A composition according to claim 1 or claim 145 wherein the tastand is hesperidin, and physiologically acceptable salts thereof.

210. A method according to claim 7 or claim 146 wherein the tastand is hesperidin, and physiologically acceptable salts thereof.

211. A composition according to claim 1 or claim 145 wherein the tastand is hesperidin methyl chalcone, and physiologically acceptable salts thereof.

212. A method according to claim 7 or claim 146 wherein the tastand is hesperidin methyl chalcone, and physiologically acceptable salts thereof.

213. A composition according to claim 1 or claim 145 wherein the tastand is inosine, and physiologically acceptable salts thereof.

214. A method according to claim 7 or claim 146 wherein the tastand is inosine, and physiologically acceptable salts thereof.

215. A composition according to claim 1 or claim 145 wherein the tastand is L-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

216. A method according to claim 7 or claim 146 wherein the tastand is L-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

217. A composition according to claim 1 or claim 145 wherein the tastand is L-threonine, and physiologically acceptable salts thereof.

218. A method according to claim 7 or claim 146 wherein the tastand is L-threonine, and physiologically acceptable salts thereof.

219. A composition according to claim 1 or claim 145 wherein the tastand is L-.beta.-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

220. A method according to claim 7 or claim 146 wherein the tastand is L-.beta.-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

221. A composition according to claim 1 or claim 145 wherein the tastand is L-aspartyl-L-tyrosine, and physiologically acceptable salts thereof.

222. A method according to claim 7 or claim 146 wherein the tastand is L-aspartyl-L-tyrocine, and physiologically acceptable salts thereof.

223. A composition according to claim 1 or claim 145 wherein the tastand is L-ornithine-.beta.-alanine dihydrochloride, and physiologically acceptable salts thereof.

224. A method according to claim 7 or claim 146 wherein the tastand is L-ornithine-.beta.-alanine dihydrochloride, and physiologically acceptable salts thereof.

225. A composition according to claim 1 or claim 145 wherein the tastand is malic acid, and physiologically acceptable salts thereof.

226. A method according to claim 7 or claim 146 wherein the tastand is malic acid, and physiologically acceptable salts thereof.

227. A composition according to claim 1 or claim 145 wherein the tastand is N-(L-aspartyl)-.alpha.-amino-cyclooctanecarboxylic acid, and physiologically acceptable salts thereof.

228. A method according to claim 7 or claim 146 wherein the tastand is N-(L-aspartyl)-.alpha.-amino-cyclooctanecarboxylic acid, and physiologically acceptable salts thereof.

229. A composition according to claim 1 or claim 145 wherein the tastand is N-(L-aspartyl)-.alpha.-amino cyclopentanecarboxylic acid, and physiologically acceptable salts thereof.

230. A method according to claim 7 or claim 146 wherein the tastand is N-(L-aspartyl)-.alpha.-amino-cyclopentanecarboxylic acid, and physiologically acceptable salts thereof.

231. A composition according to claim 1 or claim 145 wherein the tastand is N-(L-aspartyl)-o-aminobenzoic acid, and physiologically acceptable salts thereof.

232. A method according to claim 7 or claim 146 wherein the tastand is N-(L-aspartyl)-o-aminobenzoic acid, and physiologically acceptable salts thereof.

233. A composition according to claim 1 or claim 145 wherein the tastand is N-(L-aspartyl)-p-aminobenzoic acid, and physiologically acceptable salts thereof.

234. A method according to claim 7 or claim 146 wherein the tastand is N-(L-aspartyl)-p-aminobenzoic acid, and physiologically acceptable salts thereof.

235. A composition according to claim 1 or claim 145 wherein the tastand is N-(p-cyanophenyl-carbamoyl)-L-aspartyl-L-phenylalanine N-(phenylcarbamoyl)-L-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

236. A method according to claim 7 or claim 146 wherein the tastand is N-(p-cyanophenyl-carbamoyl)-L-aspartyl-L-phenylalanine N-(phenylcarbamoyl)-L-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

237. A composition according to claim 1 or claim 145 wherein the tastand is neodiosmin, and physiologically acceptable salts thereof.

238. A method according to claim 7 or claim 146 wherein the tastand is neodiosmin, and physiologically acceptable salts thereof.

239. A composition according to claim 1 or claim 145 wherein the tastand is p-anisate, and physiologically acceptable salts thereof.

240. A method according to claim 7 or claim 146 wherein the tastand is p-anisate, and physiologically acceptable salts thereof.

241. A composition according to claim 1 or claim 145 wherein the tastand is phenoxyacetic acid, and physiologically acceptable salts thereof.

242. A method according to claim 7 or claim 146 wherein the tastand is phenoxyacetic acid, and physiologically acceptable salts thereof.

243. A composition according to claim 1 or claim 145 wherein the tastand is syringic acid, and physiologically acceptable salts thereof.

244. A method according to claim 7 or claim 145 wherein the tastand is syringic acid, and physiologically acceptable salts thereof.

245. A composition according to claim 1 or claim 145 wherein the tastand is tartaric acid, and physiologically acceptable salts thereof.

246. A method according to claim 7 or claim 146 wherein the tastand is tartaric acid, and physiologically acceptable salts thereof.

247. A composition according to claim 1 or claim 145 wherein the tastand is taurine, and physiologically acceptable salts thereof.

248. A method according to claim 7 or claim 146 wherein the tastand is taurine, and physiologically acceptable salts thereof.

249. A composition according to claim 1 or claim 145 wherein the tastand is uracil, and physiologically acceptable salts thereof.

250. A method according to claim 7 or claim 146 wherein the tastand is uracil, and physiologically acceptable salts thereof.

251. A composition according to claim 1 or claim 145 wherein the tastand is uric acid, and physiologically acceptable salts thereof.

252. A method according to claim 7 or claim 146 wherein the tastand is uric acid, and physiologically acceptable salts thereof.

253. A composition according to claim 1 or claim 145 wherein the tastand is xanthosine 5' monophosphate, and physiologically acceptable salts thereof.

254. A method according to claim 7 or claim 146 wherein the tastand is xanthosine 5' monophosphate, and physiologically acceptable salts thereof.

255. A composition according to claim 1 or claim 145 wherein the tastand is 1-hydroxy-2-naphthoate, and physiologically acceptable salts thereof.

256. A method according to claim 7 or claim 146 wherein the tastand is 1-hydroxy-2-naphthoate, and physiologically acceptable salts thereof.

257. A composition according to claim 1 or claim 145 wherein the tastand is 2-methyl-3-nitroaniline, and physiologically acceptable salts thereof.

258. A method according to claim 7 or claim 146 wherein the tastand is 2-methyl-3-nitroaniline, and physiologically acceptable salts thereof.

259. A composition according to claim 1 or claim 145 wherein the tastand is 2-hydroxyphenylacetic acid, and physiologically acceptable salts thereof.

260. A method according to claim 7 or claim 146 wherein the tastand is 2-hydroxyphenylacetic acid, and physiologically acceptable salts thereof.

261. A composition according to claim 1 or claim 145 wherein the tastand is 2-amino tere-phthalic acid, and physiologically acceptable salts thereof.

262. A method according to claim 7 or claim 146 wherein the tastand is 2-amino tere-phthalic acid, and physiologically acceptable salts thereof.

263. A composition according to claim 1 or claim 145 wherein the tastand is 3-methoxyphenyl acetic acid, and physiologically acceptable salts thereof.

264. A method according to claim 7 or claim 146 wherein the tastand is 3-methoxyphenyl acetic acid, and physiologically acceptable salts thereof.

265. A composition according to claim 1 or claim 145 wherein the tastand is 3-hydroxy-2-naphthoic acid, and physiologically acceptable salts thereof.

266. A method according to claim 7 or claim 146 wherein the tastand is 3-hydroxy-2-naphthoic acid, and physiologically acceptable salts thereof.

267. A composition according to claim 1 or claim 145 wherein the tastand is 4-aminosalicylic acid, and physiologically acceptable salts thereof.

268. A method according to claim 7 or claim 146 wherein the tastand is 4-aminosalicylic acid, and physiologically acceptable salts thereof.

269. A composition according to claim 1 or claim 145 wherein the tastand is 2,4-dihydroxybenzoic acid, and physiologically acceptable salts thereof.

270. A method according to claim 7 or claim 146 wherein the tastand is 2,4-dihydroxybenzoic acid, and physiologically acceptable salts thereof.

271. A composition according to claim 1 or claim 145 wherein the tastand is 2,6-dihydroxybenzoic acid, and physiologically acceptable salts thereof.

272. A method according to claim 7 or claim 146 wherein the tastand is 2,6-dihydroxybenzoic acid, and physiologically acceptable salts thereof.

273. A composition according to claim 1 or claim 145 wherein the tastand is 3,4-dihydroxyphenylacetic acid, and physiologically acceptable salts thereof.

274. A method according to claim 7 or claim 146 wherein the tastand is 3,4-dihydroxyphenylacetic acid, and physiologically acceptable salts thereof.

275. A composition according to claim 1 or claim 145 wherein the tastand is 2,4,6-trihydroxybenzoic acid, and physiologically acceptable salts thereof.

276. A method according to claim 7 or claim 146 wherein the tastand is 2,4,6-trihydroxybenzoic acid, and physiologically acceptable salts thereof.

277. A composition according to claim 1 or claim 145 wherein the tastand is lactic acid, and physiologically acceptable salts thereof.

278. A method according to claim 7 or claim 146 wherein the tastand is lactic acid, and physiologically acceptable salts thereof.

279. A composition according to claim 1 or claim 145 wherein the tastand is N-(p-cyanophenylcarbamoyl)-L-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

280. A method according to claim 7 or claim 146 wherein the tastand is N-(p-cyanophenylcarbamoyl)-L-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

281. A composition according to claim 1 or claim 145 wherein the tastand is N-(p-nitrophenylcarbamoyl)-L-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

282. A method according to claim 7 or claim 146 wherein the tastand is N-(p-nitrophenylcarbamoyl)-L-aspartyl-L-phenylalanine, and physiologically acceptable salts thereof.

283. A composition according to claim 1 or claim 145 wherein the tastand is L-aspartyl-L-aspartic acid, and physiologically acceptable salts thereof.

284. A method according to claim 7 or claim 146 wherein the tastand is L-aspartyl-L-aspartic acid, and physiologically acceptable salts thereof.

285. A composition according to claim 1 or claim 145 wherein the eatable comprises a low calorie formulation.

286. A composition according to claim 1 or claim 145 wherein the eatable comprises potassium chloride.

287. A composition according to claim 1 or claim 145 wherein the eatable comprises sodium chloride.

288. A composition according to claim 1 or claim 145 wherein the eatable is a beverage.

289. A composition according to claim 1 or claim 145 wherein the eatable comprises polydextrose.

290. A composition for improving the taste of a eatable which contains a component which produces an undesirable taste sensation comprising:
1. at least one tastand, 2. an eatable with an undesirable taste, and 3. a masker wherein a reduced amount of masker is needed.

291. A composition according to claim 290 wherein the masker is a sweetener.

292. A composition according to claim 291 wherein the sweetener is low intensity sweetener.

293. A composition according to claim 291 wherein the sweetener is high intensity sweetener.

294. A composition according to claim 290 wherein the masker is a spice.

295. A method for improving the taste of a eatable which contains a component which produces an undesirable taste sensation comprising:
1. at least one tastand, 2. an eatable with an undesirable taste, and 3. a masker wherein a reduced amount of masker agent is needed.

296. A method according to claim 295 wherein the masker is a sweetener.

297. A method according to claim 296 wherein the sweetener is low intensity sweetener.

298. A method according to claim 296 wherein the sweetener is high intensity sweetener.

299. A method according to claim 295 wherein the masker is a spice.

300. A method for improving the taste of a beverage which contains a component which produces an undesirable taste sensation, said method comprising:
adding to said beverage a tastand selected from the group consisting of: L-aspartyl-L-phenylalanine, taurine, .beta.-alanine, 2,4-dihydroxybenzoic acid, 2,4,6-trihydroxybenzoic acid and p??siologically acceptable salts of any and/or all of the foregoing and mixtures thereof.

301. The method of claim 300 wherein said beverage further contains a sweetener.

302. The method of claim 301 wherein said undesirable taste component results from a component other than said sweetener.

303. The method of claim 301 wherein said sweetener comprises a carbohydrate.

304. The method of claim 247 wherein said beverage comprises a soft drink containing at least one high intensity sweetener.

305. The method of claim 304 wherein said high intensity sweetener is selected from one or more members of the group consisting of:
L-aspartyl-L-phenylalanine methyl ester; saccharin; L-aspartyl-D-alanine-N-(2,2,4,4-tetramethyl thiatan-3-yl)amide; 1,6-dichloro-1,6-dideoxy-.beta.-D-fructofuranoysl-4-chloro-4-deoxy-.alpha.-D-galacto-pyranoside; 6-methyl-1,2,3-oxathiazin-4(3H)-one-2,2-dioxide; 6-methyl-1,2,3-oxathiazin-4(3H)-one-2,2-dioxide potassium salt; cyclohexylsulfamic acid; N-(L-aspartyl)-N' (2,2,5,5-tetramethylcyclopentanoyl)-1,1-diaminoethane; guanidinium class sweeteners;
dihydrochalcone class sweeteners; stevioside;
miraculin; thaumatin;
and physiologically acceptable salts of any and/or all of the foregoing.

306. The method of claim 304 wherein said high intensity sweetener comprises L-aspartyl-L-phenylalanine methyl ester or a physiologically acceptable salt thereof.

307. In a foodstuff containing potassium chloride, the improvement comprising:
a tastand in said foodstuff which is selected from the group consisting of: L-aspartyl-L-phenylalanine, taurine, .beta.-alanine and 2,4-dihydroxybenzoic acid and physiologically acceptable salts of any and/or all of the foregoing.

308. The improvement of claim 307 wherein said foodstuff comprises a table salt.

309. The improvement of claim 307 wherein said foodstuff comprises a soup.

310. The improvement of claim 307 wherein said foodstuff comprises a snack food.

311. The improvement of claim 307 wherein said foodstuff comprises a salted savory.

312. In a foodstuff containing a bulking agent which produces an undesirable taste sensation, the improvement which comprises:
a tastand in said foodstuff, said tastand selected from the group consisting of: L-aspartyl-L-phenylalanine, taurine, .beta.-alanine and 2,4-dihydroxybenzoic acid and physiologically acceptable salts of any and/or all of the foregoing.

313. The improvement of claim 312 wherein said bulking agent comprises a polymeric carbohydrate.

314. A method for improving the taste of a eatable which contains a component which produces an undesirable taste sensation, said method comprising:
adding to said eatable L-aspartyl-L-phenylalanine and physiologically acceptable salts of any and/or all of the foregoing and mixtures thereof.

315. A method according to claim 314 wherein said the methodf accodin wherein said component with an undesirable taste comprises comprises L-aspartyl-L-phenylalanine methyl ester.