Flavanone compounds and their use as flavour modifiers - Patents.com

Abstract

The present disclosure generally relates to 3-alkoxyflavanone compounds and the use of such compounds to impart and / or enhance sweetness, mask bitterness, improve texture, or mask astringency. In certain embodiments, such compounds are used in combination with other flavonoids or dihydrochalcones. In certain aspects, the present disclosure provides ingestible compositions comprising such flavanone compounds. In some related aspects, the ingestible compositions are or are included in various flavored products, such as food, beverage products, pharmaceuticals, or oral care products.

Description

[Technical field]

[0001] The present disclosure generally relates to 3-alkoxyflavanone compounds and the use of such compounds to impart and / or enhance sweetness, mask bitterness, improve texture, or mask astringency. In certain embodiments, such compounds are used in combination with other flavonoids or dihydrochalcones. In certain aspects, the present disclosure provides ingestible compositions comprising such flavanone compounds. In some related aspects, the ingestible compositions are or are included in various flavored products, such as food, beverage products, pharmaceuticals, or oral care products.

[0002] 2. Description of Related Art The gustatory system provides sensory information about the chemical composition of the external world. Taste transduction is one of the more sophisticated forms of chemically triggered sensation in animals. Taste signaling is found throughout the animal kingdom, from the simplest metazoans to the most complex vertebrates. Mammals are thought to possess five basic taste modalities: sweet, bitter, sour, salty, and umami.

[0003] Sweetness is the most commonly perceived taste when eating foods rich in sugars. Mammals generally perceive sweetness as a pleasant sensation, provided it is not excessive. Caloric sweeteners such as sucrose and fructose are the prototypical examples of sweet tastants. Although a variety of non-caloric and low-caloric alternatives exist, these caloric sweeteners remain the primary means by which edible products induce the perception of sweetness upon consumption.

[0004] Metabolic disorders and associated conditions, such as obesity, diabetes, and cardiovascular disease, are major public health concerns worldwide. And their prevalence is increasing at an alarming rate in nearly all developed countries. Caloric sweeteners are a key factor contributing to this trend, as they are included in a variety of packaged food and beverage products to make them more palatable to consumers. In many cases, non-caloric or low-caloric substitutes can be used in foods and beverages in place of sucrose or fructose. Yet, these compounds impart a sweetness that is different from that of caloric sweeteners and are not seen by many consumers as suitable replacements. Moreover, such compounds can be difficult to incorporate into certain products. In some cases, they can be used as a partial replacement for caloric sweeteners, but their presence alone can cause many consumers to perceive unpleasant off-tastes, including astringency, bitterness, and metallic and licorice tastes. Thus, low-calorie sweeteners face certain challenges to their adoption.

[0005] Sweetness enhancement provides an alternative approach to overcome some of the adoption challenges faced by low-calorie sweeteners. Such compounds can be used in combination with sucrose or fructose to enhance sweetness, thereby allowing the use of smaller amounts of such calorie sweeteners in various food or beverage products. However, such compounds nevertheless change the perceived taste of sweeteners in addition to enhancing the perceived sweetness of primary sweeteners. Thus, many consumers find that consuming such sweetness-enhanced products is less enjoyable compared to more caloric non-enhanced alternatives. Thus, there is a continuing need to discover compounds that enhance the sweetness of calorie sweeteners without altering the perceived taste to the detriment of the pleasure consumers experience when eating or drinking products that contain such sweeteners.

[0006] overview The present disclosure relates to the discovery that certain flavanones and related compounds impart and / or enhance sweetness with a more natural taste and can also be used in some cases to mask bitterness, improve texture, or mask astringency.

[0007] In a first aspect, the present disclosure provides a flavor modifying compound, which is a compound of formula (I): [ka] or a salt thereof, R 1 ,R 2 ,R 3 and R 4 are each independently a hydrogen atom, C 1-6 Alkyl, -OH or -O-(C 1-6 alkyl), R 5 ,R 6 ,R 7 ,R 8 and R 9 are each independently a hydrogen atom, C 1-6 Alkyl, -OH, or -O-(C 1-6 alkyl), R X is C 1-6 It is an alkyl.

[0008] In a second aspect, the present disclosure provides the use of a flavor modifying compound of the first aspect to enhance the sweetness of an ingestible composition. In certain related aspects, the present disclosure provides a method of enhancing the sweetness of an ingestible composition, the method comprising introducing a flavor modifying compound of the first aspect into the ingestible composition. In some embodiments, the ingestible composition comprises one or more sweeteners, such as caloric or non-caloric sweeteners. In some embodiments, the ingestible composition comprises one or more flavonoids or dihydrochalcones.

[0009] In a third aspect, the present disclosure provides the use of a flavor modifying compound of the first aspect to reduce the bitterness of an ingestible composition. In certain related aspects, the present disclosure provides a method of reducing the bitterness of an ingestible composition, the method comprising introducing a flavor modifying compound of the first aspect into the ingestible composition. In some embodiments, the ingestible composition comprises one or more bitter tastants, such as certain high-intensity sweeteners, caffeine, tannins, pharmaceutical APIs, etc. In some embodiments, the ingestible composition comprises one or more flavonoids or dihydrochalcones.

[0010] In a fourth aspect, the present disclosure provides a use of the flavor modifying compound of the first aspect to reduce the astringency of an ingestible composition. In certain related aspects, the present disclosure provides a method for reducing the astringency of an ingestible composition, the method comprising introducing a flavor modifying compound of the first aspect into the ingestible composition. In some embodiments, the ingestible composition comprises one or more astringent compounds. Non-limiting examples of such uses and methods include reducing the lingering licorice aftertaste of certain high-intensity sweeteners, such as stevia-based high-intensity sweeteners. In some embodiments, the ingestible composition comprises one or more flavonoids or dihydrochalcones.

[0011] In a fifth aspect, the present disclosure provides the use of a flavor modifying compound of the first aspect to improve the texture of an ingestible composition. In certain related aspects, the present disclosure provides a method of improving the texture of an ingestible composition, the method comprising introducing a flavor modifying compound of the first aspect into the ingestible composition. In some embodiments, the ingestible composition comprises one or more flavonoids or dihydrochalcones.

[0012] In a sixth aspect, the present disclosure provides an ingestible composition comprising one or more flavor modifying compounds of the first aspect. In some embodiments, the ingestible composition comprises one or more sweeteners. In some embodiments, the ingestible composition comprises one or more bitter tastants, such as high intensity sweeteners or specific bitter compounds.

[0013] In a seventh aspect, the present disclosure provides a flavored product comprising the ingestible composition of the sixth aspect. In some embodiments, the flavored product is a food or beverage product. In some embodiments, the flavored product is an oral care product or a pharmaceutical product.

[0014] Further aspects and embodiments thereof are described below in the detailed description, drawings, abstract, and claims.

[0015] The following drawings are provided for the purpose of illustrating various embodiments of the compositions and methods disclosed herein. The drawings are provided for illustrative purposes only and are not intended to illustrate any preferred compositions or preferred methods or to cause any limitations on the scope of the claimed invention. [Brief description of the drawings]

[0016] [Figure 1] 1 shows a chemical formula representing the flavor modifying compounds disclosed herein, wherein R1-R9 are each independently a hydrogen atom, a C1-6 alkyl, -OH or -O-(C1-6 alkyl), and R X is a C1-6 alkyl.

[0017] Detailed Description The following detailed description describes various aspects and embodiments provided herein. The description should be read from the perspective of one of ordinary skill in the art. As such, it does not necessarily include information that is known to such a person of ordinary skill in the art.

[0018] definition The following terms and phrases have the meanings set forth below unless otherwise specified herein. This disclosure may use other terms and phrases that are not expressly defined herein. Such other terms and phrases have the meanings that they would have within the context of this disclosure to a person skilled in the art. In some cases, a term or phrase may be defined in the singular or plural. In such cases, it is understood that any term in the singular form can include its plural counterpart, and vice versa, unless expressly indicated to the contrary.

[0019] "Sweetener" refers to a compound or an ingestibly acceptable salt thereof that induces a detectable sweet taste in a subject, e.g., a compound that activates the T1R2 and T1R3 taste receptors in vivo or in vitro.

[0020] "Bitter tastant" refers to a compound or an ingestibly acceptable salt thereof that induces a detectable bitter taste in a subject, e.g., a compound that activates one or more T2R taste receptors in vivo or in vitro.

[0021] As used herein, "C a ~C b " or "C a-b " (where "a" and "b" are integers) refers to the number of carbon atoms in a particular group. That is, the group may contain at least "a" and at most "b" carbon atoms. Thus, for example, "C1-C4 alkyl" or "C 1-4 An "alkyl" group refers to all alkyl groups having 1 to 4 carbons, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-.

[0022] As used herein, "alkyl" refers to a straight or branched hydrocarbon chain that is fully saturated (i.e., contains no double or triple bonds). In some embodiments, the alkyl group comprises 1 to 20 carbon atoms (wherever it appears herein, a numerical range such as "1 to 20" refers to each integer within the given range. For example, "1 to 20 carbon atoms" means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to 20 carbon atoms, although this definition also encompasses the occurrence of the term "alkyl" where no numerical range is specified). The alkyl group may also be a medium size alkyl having 1 to 9 carbon atoms. The alkyl group may also be a lower alkyl having 1 to 4 carbon atoms. The alkyl group may also be a "C 1-4 By way of example only, "C 1-4 "Alkyl" indicates that the alkyl chain has 1 to 4 carbon atoms, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, and the like. Unless indicated to the contrary, the term "alkyl" refers to a group that is not further substituted.

[0023] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, reference to a "substituent" includes a single substituent as well as two or more substituents, and the like.

[0024] As used herein, "for example," "for instance," "such as," or "including" are meant to introduce examples that further clarify a more general subject matter. Unless expressly stated otherwise, such examples are provided only as an aid in understanding the embodiments set forth in this disclosure and are not meant to be limiting in any way. These phrases do not imply any kind of preference for the disclosed embodiments.

[0025] As used herein, "comprise" or "comprises" or "comprising" or "comprised of" refers to an open group, meaning that the group can include additional members in addition to those explicitly listed. For example, the phrase "comprising A" means that A must be present, but other members may be present. The terms "include," "have," and "composed of" and their grammatical variations have the same meaning. In contrast, "consist of" or "consists of" or "consisting of" refers to a closed group. For example, "consisting of A" means that only A is present.

[0026] As used herein, "optionally" means that the subsequently described event may or may not occur. In some embodiments, the optional event does not occur. In some other embodiments, the optional event occurs one or more times.

[0027] As used herein, "or" should be given its broadest reasonable interpretation and should not be limited to an either / or configuration. Thus, the phrase "comprising A or B" means that A is present and not B, or B is present and not A, or both A and B are present. Furthermore, if, for example, A defines a class that can have multiple members, e.g., A1 and A2, one or more members of the class can be present at the same time.

[0028] Chemical structures are often shown using a "skeletal" format, such that the carbon atoms are not explicitly shown and the hydrogen atoms attached to carbon atoms are omitted entirely. For example, the structure [ka] represents butane (i.e., n-butane). Additionally, aromatic groups such as benzene are represented by showing one of the contributing resonance structures. For example, the structure [ka] represents toluene.

[0029] As used herein, the term "flavor modifying compound" refers to any compound of formula (I) or a salt thereof, and any embodiment thereof described herein.

[0030] Other terms not included in this subsection are defined elsewhere in this description.

[0031] Flavor-modifying compounds In certain aspects, the present disclosure provides a flavor modifying compound, which is a compound of formula (I): [ka] or a salt thereof, R 1 ,R 2 ,R 3 and R 4are each independently a hydrogen atom, C 1-6 Alkyl, -OH or -O-(C 1-6 alkyl), R 5 ,R 6 ,R 7 ,R 8 and R 9 are each independently a hydrogen atom, C 1-6 Alkyl, -OH, or -O-(C 1-6 alkyl), R X is C 1-6 It is an alkyl.

[0032] Variable R 1 ,R 2 ,R 3 , and R 4 can have any suitable value within the above definition. In some embodiments, R 1 ,R 2 ,R 3 , and R 4 are, independently of each other, a hydrogen atom, methyl, -OH (hydroxy) or -O-CH3 (methoxy).

[0033] In some embodiments of any of the foregoing embodiments, R 1 ,R 2 ,R 3 , and R 4 In some further such embodiments, at least one of R 1 ,R 2 ,R 3 , and R 4 At least two of the are hydrogen atoms.

[0034] In some embodiments of any of the foregoing embodiments, R 2 and R 4 is a hydrogen atom, and R 1 and R 3 are, independently of each other, a hydrogen atom, methyl, hydroxy, or methoxy. In some such embodiments, R 1In some other such embodiments, R 1 is a hydrogen atom. In some embodiments, R 3 is hydroxy or methoxy. In some other such embodiments, R 3 is a hydrogen atom. In some embodiments, R 3 is hydroxy. In some embodiments, R 3 is methoxy.

[0035] In some embodiments of any of the foregoing embodiments, R 1 and R 3 is a hydrogen atom, and R 2 and R 4 are, independently of each other, a hydrogen atom, methyl, hydroxy, or methoxy. In some such embodiments, R 4 In some other such embodiments, R 4 is a hydrogen atom. In some embodiments, R 2 is hydroxy or methoxy. In some other such embodiments, R 2 is a hydrogen atom. In some embodiments, R 4 is hydroxy. In some embodiments, R 2 is methoxy. In some embodiments, R 1 ,R 2 ,R 3 , and R 4 Each of is a hydrogen atom.

[0036] Variable R 5 ,R 6 ,R 7 ,R 8 , and R 9 can have any suitable value within the above definition. In some embodiments, R 5 ,R 6 ,R 7 ,R 8 , and R 9 are, independently of each other, a hydrogen atom, methyl, -OH (hydroxy) or -O-CH3 (methoxy).

[0037] In some embodiments of any of the foregoing embodiments, R 5 ,R 6 ,R 7 ,R 8 , and R 9 At least two of R are hydrogen atoms. 5 ,R 6 ,R 7 ,R 8 , and R 9 At least three of R are hydrogen atoms. 5 ,R 6 ,R 7 ,R 8 , and R 9 At least four of the are hydrogen atoms.

[0038] In some embodiments of any of the foregoing embodiments, R 5 and R 9 is a hydrogen atom, and R 6 ,R 7 , and R 8 are, independently of each other, a hydrogen atom, methyl, hydroxy, or methoxy. In some embodiments of any of the foregoing embodiments, R 5 ,R 6 , and R 9 is a hydrogen atom, and R 7 and R 8 are, independently of each other, a hydrogen atom, methyl, hydroxy, or methoxy. In some such embodiments, R 7 In some further such embodiments, R 7 In some other such embodiments, R 7 In some other such embodiments, R 7 is a hydrogen atom. In some embodiments, R 8 In some other such embodiments, R 8 is a hydrogen atom. In some embodiments, R 7is hydroxy and R 8 is a hydrogen atom. In some embodiments, R 7 is hydroxy and R 8 is hydroxy. In some embodiments, R 7 is methoxy and R 8 is hydroxy.

[0039] Variable R X can have any suitable value within the above definition. In some embodiments, R X is C 1-4 In some embodiments, R X is methoxy, ethoxy, or isopropyl. In some embodiments, R X is methoxy or ethoxy. In some embodiments, R X is ethoxy. In some embodiments, R X is methoxy.

[0040] Table 1 provides examples of flavor-modifying compounds of the present disclosure. In some embodiments, the flavor-modifying compound is compound 101 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 102 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 103 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 104 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 105 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 106 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 107 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 108 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 109 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 110 or a edible salt thereof. In some embodiments, the flavor-modifying compound is compound 111 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 112 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 113 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 114 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 115 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 116 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 117 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 118 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 119 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 120 or a edible salt thereof.In some embodiments, the flavor altering compound is compound 121 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 122 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 123 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 124 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 125 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 126 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 127 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 128 or a edible salt thereof. In some embodiments, the flavor altering compound is compound 129 or a edible salt thereof.

[0041] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6]

[0042] When the flavor modifying compounds disclosed herein have at least one chiral center, they can exist as individual enantiomers and diastereomers, or as mixtures of such isomers. In some embodiments related to the second aspect, the sweetening enhancing compounds have substantial enantiomeric purity.

[0043] Separation of individual isomers or selective synthesis of individual isomers can be achieved by applying various methods well known to those skilled in the art. Unless otherwise indicated (e.g., when the stereochemistry of a chiral center is explicitly indicated), all such isomers and mixtures thereof are included within the scope of the compounds disclosed herein. Furthermore, the compounds disclosed herein may exist in one or more crystalline or amorphous forms. Unless otherwise indicated, all such forms are included within the scope of the compounds disclosed herein, including any polymorphs. Furthermore, some of the compounds disclosed herein may form solvates with water (i.e., hydrates) or common organic solvents. Unless otherwise indicated, such solvates are included within the scope of the compounds disclosed herein.

[0044] Those skilled in the art will recognize that some structures described herein may be resonance forms or tautomers of compounds that may be significantly represented, even kinetically, by other chemical structures. Those skilled in the art will recognize that such structures may only represent a small portion of a sample of such compounds. Although such compounds are considered to be within the scope of the structures shown, such resonance forms or tautomers are not represented herein.

[0045] Isotopes may be present in the compounds described. Each chemical element represented in a compound structure may include any isotope of that element. For example, in a compound structure, a hydrogen atom may be explicitly disclosed or understood to be present in the compound. At any position of the compound where a hydrogen atom may be present, the hydrogen atom may be any isotope of hydrogen, including but not limited to hydrogen-1 (protium) and hydrogen-2 (deuterium). Thus, reference to a compound herein encompasses all possible isotopic forms, unless the context clearly indicates otherwise.

[0046] In some embodiments, the flavor modifying compounds disclosed herein can form acid salts and / or base salts due to the presence of phenolic, amino and / or carboxyl groups or groups similar thereto. Food-acceptable acid addition salts can be formed with inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Food-acceptable salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, bases containing sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like, with ammonium, potassium, sodium, calcium, and magnesium salts being particularly preferred. In some embodiments, treatment of the compounds disclosed herein with an inorganic base results in the loss of a labile hydrogen from the compound, forming Li + ,Na + ,K + ,Mg 2+ and Ca 2+ Salt forms containing inorganic cations such as , , and the like are obtained. Organic bases from which salts can be derived include, for example, primary, secondary and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine and ethanolamine. In some embodiments, the salt is an edible acceptable salt, which is a salt suitable for inclusion in ingestible compositions such as food or beverage products. In some embodiments, the edible acceptable salt is a sodium salt or a potassium salt.

[0047] Uses and Methods In certain aspects, the present disclosure provides the use of a flavor modifying compound of the first aspect to enhance the sweetness of an ingestible composition. In certain related aspects, the present disclosure provides a method of enhancing the sweetness of an ingestible composition, the method comprising introducing a flavor modifying compound of the first aspect into the ingestible composition.

[0048] In certain aspects, the present disclosure provides the use of a flavor modifying compound of the first aspect to reduce the bitterness of an ingestible composition. In certain related aspects, the present disclosure provides a method of reducing the bitterness of an ingestible composition, the method comprising introducing a flavor modifying compound of the first aspect into the ingestible composition.

[0049] In certain aspects, the disclosure provides for the use of a flavor modifying compound of the first aspect to reduce the astringent taste of an ingestible composition (such as the lingering aftertaste of high intensity sweeteners or the aftertaste of licorice).In certain related aspects, the disclosure provides a method of reducing the astringent taste of an ingestible composition, the method comprising introducing a flavor modifying compound of the first aspect into the ingestible composition.

[0050] In certain aspects, the present disclosure provides the use of a flavor modifying compound of the first aspect to improve the texture of an ingestible composition. In certain related aspects, the present disclosure provides a method of improving the texture of an ingestible composition, the method comprising introducing a flavor modifying compound of the first aspect into the ingestible composition.

[0051] The aforementioned uses and methods include ingestible compositions. In addition to the ingestible composition features described above, the ingestible composition may incorporate any feature or combination of features set forth below.

[0052] Ingestible Composition In certain aspects, the present disclosure provides ingestible compositions comprising a flavor modifying compound according to the above embodiments. When incorporated into or used in an ingestible composition, the flavor modifying compound is used or incorporated into the ingestible composition at a concentration ranging from 0.01 ppm to 1000 ppm, or from 0.01 ppm to 900 ppm, or from 0.01 ppm to 800 ppm, or from 0.01 ppm to 700 ppm, or from 0.01 ppm to 600 ppm, or from 0.1 ppm to 500 ppm, or from 0.1 ppm to 400 ppm, or from 0.1 ppm to 300 ppm, or from 0.1 ppm to 200 ppm, or from 1 ppm to 100 ppm, or from 1 ppm to 80 ppm, or from 1 ppm to 60 ppm, or from 1 ppm to 50 ppm, or from 1 ppm to 40 ppm.

[0053] In some embodiments, the ingestible composition comprises one or more bitter tastants. In some embodiments, the bitter tastants are high intensity sweeteners, such as acesulfame potassium, aspartame, neotame, cyclamate, saccharin, sucralose, steviol glycosides (e.g., rebaudioside A, rebaudioside B, rebaudioside M, rebaudioside D, or rebaudioside E), and mogrosides (e.g., mogroside III, mogroside IV, mogroside V, siamenoside I, isomogroside V, mogroside IV, E , Isomogroside IV, Mogroside III E , 11-oxomogroside V, or the 1,6-α isomer of siamenoside I). The flavour modifying compounds may therefore be suitable for use in reduced or zero sugar products to reduce the bitter taste imparted by low or zero calorie sweeteners.

[0054] In some embodiments, the bitter tastant is a potassium salt, such as potassium chloride, which is often used as a partial or complete replacement for sodium chloride in certain low- or zero-sodium foods. Thus, the flavor-modifying compounds may be suitable for use in such products to reduce the bitterness imparted by the potassium salt.

[0055] In some embodiments, the bitter tastant is a non-animal protein, such as vegetable protein, algae protein, or mycoprotein. In some embodiments, the ingestible composition comprises vegetable protein. Non-limiting examples of vegetable protein include pea protein, soy protein, almond protein, cashew protein, canola (rapeseed) protein, chickpea protein, broad bean protein, sunflower protein, wheat protein, oat protein, barley protein, and potato protein. Such non-animal proteins are often used as partial or complete replacements for animal proteins in dairy and meat analogues. Therefore, flavor modifying compounds can be suitably used in such products to reduce the bitterness imparted by non-animal proteins. By blocking the bitterness of such proteins, flavor modifying compounds can reduce the perceived grain and herbaceous odors experienced by consumers.

[0056] In some embodiments, the bitter tastants are caffeine, quinine, green tea, catechins, polyphenols (such as polyphenol antioxidants), tannins, green robusta coffee extract, green coffee extract, menthol, etc. Such compounds are commonly present in a variety of natural foods, such as tea and coffee, as well as packaged foods, such as instant tea, instant coffee, packaged beverages, etc. When one or more such bitter tastants are present, flavor-modifying compounds are suitably used to mask the bitterness of such compounds and improve the taste of the product as perceived by the consumer.

[0057] In some embodiments, the bitter tastant is a pharmaceutical compound.Non-limiting examples of pharmaceutical compounds with bitter taste include atropine, brinzolamide, chloramphenicol, chloroquine, clindamycin, dexamethasone, digoxin, diltiazem, diphenhydramine, docusate, dorzolamide, doxepin, doxylamine, enalapril, erythromycin, esomeprazole, famotidine, gabapentin, ginkgolide A, guaifenesin, L-histidine, lomefloxacin, methylprednisolone, ofloxacin, oleuropein, oxyphenonium, pirenzepine, prednisone, ranitidine, trapidil, trimethoprim, and cetirizine.When one or more such pharmaceutical compounds are used in oral pharmaceutical preparations, the taste-modifying compound is preferably used to block the bitterness of such compounds and improve the taste of the pharmaceutical product as perceived by consumers.

[0058] In some embodiments, the bitter tastant is an oral care ingredient. Many oral care ingredients impart a bitter taste, which must be masked or blocked to improve consumer acceptance of the product. Non-limiting examples of such oral care ingredients include menthol, menthol analogs, mint extracts, sodium bicarbonate, alkali metal salts of peroxymonosulfate (potassium peroxymonosulfate), cetylpyridinium chloride, lauramidopropyl betaine, cocamidopropyl betaine, arginine, hydrogen peroxide, chlorhexidine gluconate, potassium nitrate, pentasodium triphosphate, tetrasodium pyrophosphate, stannous fluoride, thymol, methyl salicylate, eucalyptol, thymol, cubebol, and any combination thereof. When one or more such oral care compounds are used in oral care products, the flavor modifying compound is preferably used to block the bitter taste of such compounds and improve the taste of the oral care product as perceived by consumers.

[0059] In some embodiments, the bitter tasting substance is a bittering agent found in citrus fruits, such as limonin, nomellin or naringin. Many citrus-containing preparations impart a bitter taste, which must be masked or blocked to improve consumer acceptance of the product. This bitter taste may in some cases be due to citrus greening disease, which causes citrus fruits to turn green before they are fully ripe. When one or more such citrus bitter tasting substances are present, the flavor modifying compound is preferably used to block the bitterness of such compounds and improve the taste of citrus products as perceived by consumers.

[0060] In some embodiments, the ingestible composition comprises one or more flavanones. In certain embodiments, such flavanones act synergistically with the flavor-modifying compounds disclosed herein to reduce bitterness, enhance sweetness perception, or reduce sourness. In some embodiments, the flavanone is eriodictyol, hesperetin, hesperidin, homoeriodictyol, naringenin, or any combination thereof. In some further embodiments, the flavanone is eriodictyol. In some other embodiments, the flavanone is homoeriodictyol. Such flavanones can be present in the ingestible composition at any suitable concentration, for example, at a concentration ranging from 0.01 ppm to 1000 ppm, or from 0.01 ppm to 900 ppm, or from 0.01 ppm to 800 ppm, or from 0.01 ppm to 700 ppm, or from 0.01 ppm to 600 ppm, or from 0.1 ppm to 500 ppm, or from 0.1 ppm to 400 ppm, or from 0.1 ppm to 300 ppm, or from 0.1 ppm to 200 ppm, or from 1 ppm to 100 ppm, or from 1 ppm to 80 ppm, or from 1 ppm to 60 ppm, or from 1 ppm to 50 ppm, or from 1 ppm to 40 ppm.

[0061] In some embodiments, the ingestible composition comprises a sweetener or a combination of sweeteners. In some embodiments, the sweetener is a sweetener composition comprising common sugar sweeteners, such as sucrose, fructose, glucose, and natural sugars, such as corn syrup (including high fructose corn syrup) or other syrups or sweetener concentrates derived from natural fruit and plant sources. In some embodiments, the sweetener is sucrose, fructose, or a combination thereof. In some embodiments, the sweetener is sucrose. In some other embodiments, the sweetener is selected from rare natural sugars, including D-allose, D-psicose, L-ribose, D-tagatose, L-glucose, L-fucose, L-albinose, D-turanose, and D-leucrose. In some embodiments, the sweetener is selected from semi-synthetic "sugar alcohol" sweeteners, such as erythritol, isomalt, lactitol, mannitol, sorbitol, xylitol, maltodextrin, etc. In some embodiments, the sweetener is selected from artificial sweeteners such as aspartame, saccharin, acesulfame-K, cyclamate, sucralose, and alitame. In some embodiments, the sweetener is selected from the group consisting of cyclamic acid, mogrosides, tagatose, maltose, galactose, mannose, sucrose, fructose, lactose, allulose, neotame and other aspartame derivatives, glucose, D-tryptophan, glycine, maltitol, lactitol, isomalt, hydrogenated glucose syrup (HGS), hydrogenated starch hydrolysates (HSH), stevioside, rebaudioside A, other sweet stevia-based glycosides, chemically modified steviol glycosides (e.g., glucosylated steviol glycosides), mogrosides, chemically modified mogrosides (e.g., glucosylated mogrosides), carrelame, and other guanidine-based sweeteners. In some embodiments, the sweetener is a combination of two or more of the sweeteners described in this paragraph.In some embodiments, the sweetener may be a combination of two, three, four or five sweeteners disclosed herein.In some embodiments, the sweetener may be sugar.In some embodiments, the sweetener may be a combination of one or more sugars and other natural and artificial sweeteners. In some embodiments, the sweetener is a sugar. In some embodiments, the sugar is cane sugar. In some embodiments, the sugar is beet sugar. In some embodiments, the sugar may be sucrose, fructose, glucose or a combination thereof. In some embodiments, the sugar may be sucrose. In some embodiments, the sugar may be a combination of fructose and glucose.

[0062] Sweeteners can also include sweetener compositions, such as one or more natural or synthetic carbohydrates, such as corn syrup, high fructose corn syrup, high maltose corn syrup, glucose syrup, sucralose syrup, hydrogenated glucose syrup (HGS), hydrogenated starch hydrolysate (HSH), or other syrups or sweetener concentrates derived from natural fruit and plant sources, or semi-synthetic "sugar alcohol" sweeteners, such as polyols. Non-limiting examples of polyols in some embodiments include erythritol, maltitol, mannitol, sorbitol, lactitol, xylitol, isomalt, propylene glycol, glycerol (glycerin), threitol, galactitol, palatinose, reduced isomaltooligosaccharides, reduced xylooligosaccharides, reduced gentiooligosaccharides, reduced maltose syrup, reduced glucose syrup, isomaltulose, maltodextrin, etc., and sugar alcohols or any other carbohydrates, or combinations thereof that can be reduced and do not adversely affect taste.

[0063] The sweetener may be a natural or synthetic sweetener, including, but not limited to, agave inulin, agave nectar, agave syrup, amazake, brazzein, brown rice syrup, coconut crystals, coconut sugar, coconut syrup, date sugar, fructans (also called inulin fiber, fructooligosaccharides or oligofructose), green stevia powder, stevia rebaudiana, rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside E, rebaudioside F, rebaudioside G, rebaudioside H, rebaudioside I ... Rebaudioside E, Rebaudioside F, Rebaudioside I, Rebaudioside H, Rebaudioside L, Rebaudioside K, Rebaudioside J, Rebaudioside N, Rebaudioside O, Rebaudioside M and other sweet stevia glycosides, stevioside, stevioside extract, honey, Jerusalem artichoke syrup, licorice root, Monk fruit (fruit, powder, or extract), Lucuma (fruit, powder, or extract), maple sap (e.g., Acer saccharum ( saccharum, Acer nigrum, Acer rubrum, Acer saccharinum, Acer platanoides, Acer negundo, Acer macrophyllum, Acer grandidentatum, Acer glabrum, Acer mono), maple syrup, maple sugar, walnut sap (including sap extracted from Juglans cinerea, Juglans nigra, Juglans ailatifolia, Juglans regia), birch sap (e.g., Betula papyrifera, Betula alleghaniensis, Betula lenta, Betula nigra,including sap extracted from Betula populifolia, Betula pendula), sycamore sap (e.g., sap extracted from Platanus occidentalis), ironwood sap (e.g., Ostrya virginiana), virginiana), muscovado, molasses (e.g., blackstrap molasses), molasses sugar, monatin, monellin, cane sugar (also called natural sugar, unrefined cane sugar, or sucrose), palm sugar, panocha, piloncillo, rapadura, raw sugar, rice syrup, sorghum, sorghum syrup, cassava syrup (also called tapioca syrup), thaumatin, yacon root, malt syrup, barley malt syrup, barley malt powder, beet sugar , cane sugar, crystalline fruit juice crystals, caramel, carbitol, carob syrup, castor sugar, hydrogenated starch hydrolysate, hydrolyzed canned juice, hydrolyzed starch, invert sugar, anethole, arabinogalactan, arop, syrup, P-4000, acesulfame potassium (also called acesulfame K or ace-K), alitame (also called aclame), advantame, aspartame, bayunoside, neotame, benzamide derivatives Body, Bernademe, Candelal, Carrelam and other guanidine sweeteners, vegetable fiber, corn sugar, coupling sugar, curculin, cyclamate, cyclocaryoside I, demerara, dextran, dextrin, saccharified malt, dulcin, sucrose, valgin, dulcoside A, dulcoside B, emulin, enoxolone, maltodextrin, saccharin, estragole, ethyl maltol, glycine, gluconic acid, glucono-lactone, glucosamine, Glucoronate, glycerol, glycine, glycyphillin, glycyrrhizin, glycyrrhetinic acid monoglucuronide, golden sugar, yellow sugar, golden syrup, granulated sugar, Jiaogulan, Hernandursin, isomerized liquid sugar, Jarab, chicory root dietary fiber, kynurenine derivatives (including N'-formyl-kynurenine, N'-acetyl-kynurenine, 6-chloro-kynurenine), galactitol, litesse,Lidicane, Lycasin, Lugusnum, Guanidine, Falannum, Mabinlin I, Mabinlin II, Maltol, Multisorb, Maltodextrin, Maltotriol, Mannosamine, Miraculin, Starch syrup, Mogrosides (including Mogroside IV, Mogroside V, and Neomogroside), Muclodiosides, Nanosugar, Naringin dihydrochalcone, Neohesperidin dihydrochalcone, Nib sugar, Nigero-oligosaccharides, Norbu, Orgy syrup, Osladin, Pekmez, Pentasine, Periandrin I, Perillaldehyde, Perillartine, Petophyllum, Phenylalanine, Phlomisoside I, Phlorogizin, Phyllodulcin, Polyglycitol syrup, Polypodoside A, Pterocaryoside A, Pterocaryoside B, Rebiana, Refiner syrup, Rub syrup syrup, rubusoside, selligueain A, shugr, siamenoside I, siraitia grosvenorii, soy oligosaccharides, splenda, SRI oxime V, steviol glycosides, steviolbioside, stevioside, strogin 1, 2 and 4, sucronic acid, sucrononate, sugar, suosan, phlorizin, super aspartame, tetrasaccharide, threitol, molasses, trilobtain, tryptophan and derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, volemitol, birch xylose, aspartame-acesulfame, asguline, and combinations or blends of any two or more thereof.

[0064] Additional sweeteners also include combinations of any two or more of any of the aforementioned sweeteners. In some embodiments, the sweetener may include a combination of two, three, four or five sweeteners disclosed herein. In some embodiments, the sweetener may be a sugar. In some embodiments, the sweetener may be a combination of one or more sugars and other natural and artificial sweeteners. In some embodiments, the sweetener is a caloric sweetener, such as sucrose, fructose, xylitol, erythritol, or combinations thereof. In some embodiments, the ingestible composition is free of, or (in some embodiments) substantially free of, stevia-derived sweeteners, such as steviol glycosides, glucosylated steviol glycosides, or rebaudiosides.

[0065] In some embodiments, the sweetener is sucrose. In some other embodiments, the sweetener is a steviol glycoside.

[0066] In some embodiments, the ingestible composition comprises an acidic tastant, such as an organic acid, non-limiting examples of which include acetic acid, malonic acid, citric acid, lactic acid, and the like.

[0067] The ingestible compositions, in certain embodiments, can include any additional ingredient or combination of ingredients commonly used in food and beverage products, including, but not limited to, Acids, including for example citric acid, phosphoric acid, ascorbic acid, sodium sulfate, lactic acid, or tartaric acid; bitter components including, for example, caffeine, quinine, green tea, catechins, polyphenols, green robusta coffee extract, green coffee extract, potassium chloride, menthol, or proteins (such as proteins and protein isolates derived from plants, algae, or fungi); Coloring agents such as caramel color, Red No. 40, Yellow No. 5, Yellow No. 6, Blue No. 1, Red No. 3, purple carrot, black carrot juice, purple sweet potato, vegetable juice, fruit juice, beta carotene, turmeric curcumin, or titanium dioxide; Preservatives, such as sodium benzoate, potassium benzoate, potassium sorbate, sodium metabisulfate, sorbic acid, or benzoic acid; Antioxidants including, for example, ascorbic acid, disodium calcium EDTA, alpha tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol, or sodium hexametaphosphate; For example, Resveratrol, Co-Q10, Omega-3 fatty acids, Theanine, Choline chloride (Cytocholine), Fibersol, Inulin (Chicory root), Taurine, Ginseng extract, Guanana extract, Ginger extract, L-Phenylalanine, L-Carnitine, L-Tartrate, D-Glucoronolactone, Inositol, Bioflavonoids, Echinacea, Ginkgo Biloba, Yerba Mate, Flaxseed oil, Garcinia cambogia lind extract, White tea extract, Ribose, Milk thistle extract, Grape seed extract, Pyroxyxine HCl (vitamin B6), Cyanoobalamin (vitamin B12), Niacinamide. vitamins or functional ingredients including sucrose, folic acid, calcium lactate, calcium pantothenate (pantothenic acid), calcium phosphate, calcium carbonate, chromium chloride, chromium polynicotinate, copper sulfate, folic acid, ferric pyrophosphate, iron, magnesium lactate, magnesium carbonate, magnesium sulfate, monopotassium phosphate, monosodium phosphate, phosphorus, potassium iodide, potassium phosphate, riboflavin, sodium sulfate, sodium gluconate, sodium polyphosphate, sodium bicarbonate, thiamine mononitrate, vitamin D3, vitamin A palmitate, zinc gluconate, zinc lactate, or zinc sulfate; Opacifiers, such as ester gun, brominated vegetable oil (BVO), or sucrose acetate isobutyrate (SAIB); Buffers containing, for example, sodium citrate, potassium citrate, or salts; For example, propylene glycol, ethyl alcohol, glycerin, gum arabic (gum acacia), maltodextrin, modified corn starch, dextrose, natural flavors, natural flavors with other natural flavors (natural flavors WONF), natural and artificial flavors, artificial flavors, flavors containing silicon dioxide, magnesium carbonate, or tricalcium phosphate; or Examples include starches and stabilizers including pectin, xanthan gum, carboxymethylcellulose (CMC), polysorbate 60, polysorbate 80, medium chain triglycerides, cellulose gel, cellulose gum, sodium caseinate, modified food starch, gum arabic (gum acacia), inulin or carrageenan.

[0068] The ingestible composition can have any suitable pH. In some embodiments, the flavor modifying compound enhances the sweetness of the sweetener under a wide range of pH, for example, from lower to neutral pH. Lower and neutral pH include, but are not limited to, pHs of 1.5 to 9.0, or 2.5 to 8.5, 3.0 to 8.0, 3.5 to 7.5, and 4.0 to 7. In certain embodiments, the compounds disclosed and described herein, individually or in combination, can enhance the perceived sweetness of a certain concentration of sweetener in a taste test at compound concentrations of 50 μM, 40 μM, 30 μM, 20 μM, or 10 μM, both at low and neutral pH values. In certain embodiments, the enhancement factor of the compounds disclosed and described herein, individually or in combination, at lower pH is substantially similar to the enhancement factor of the compounds at neutral pH. Such consistent sweetness enhancing properties over a wide range of pH allow the compounds disclosed and described herein to be widely used, individually or in combination, in a wide variety of foods and beverages.

[0069] In some embodiments, the ingestible composition comprises a flavoring agent. Any suitable flavoring agent can be used. In some embodiments, the flavoring agent comprises synthetic flavor oils and flavoring aromatics or oils, oleoresins, and extracts derived from plants, leaves, flowers, fruits, and the like, or combinations thereof. Non-limiting examples of flavoring oils include spearmint oil, cinnamon oil, oil of wintergreen (methyl salicylate), peppermint oil, peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, oil of nutmeg, allspice, oil of sage, mace, oil of bitter almond, and cassia oil. Non-limiting examples of other flavors include natural and synthetic fruit flavors such as vanilla, citrus oils including lemon, orange, lime, grapefruit, yazu, and sudachi, fruit extracts including apple, pear, peach, grape, blueberry, strawberry, raspberry, cherry, plum, pineapple, watermelon, apricot, banana, melon, apricot, plum, cherry, raspberry, blackberry, tropical fruits, mango, mangosteen, pomegranate, papaya, and the like.Other possible flavors include milk, butter, cheese, cream, and yogurt; vanilla; tea or coffee flavors, such as green tea, oolong tea, tea, cocoa, chocolate, and coffee; mint flavors, such as peppermint, spearmint, and peppermint; asafetida, ajowan, anise, angelica, fennel, allspice, cinnamon, chamomile, mustard, cardamom, caraway, cumin, clove, pepper, coriander, sassafras, savory, and Zanthoxyli. Fructus flavor, perilla flavor, juniper berry flavor, ginger flavor, star anise flavor, horseradish flavor, thyme flavor, tarragon flavor, dill flavor, chili pepper flavor, nutmeg flavor, basil flavor, marjoram flavor, rosemary flavor, bay leaf flavor, wasabi (Japanese wasabi) flavor, alcohol flavor such as wine flavor, whiskey flavor, brandy flavor, rum flavor, gin flavor, and liqueur flavor, flower flavor, and vegetable flavor such as onion flavor, garlic flavor, cabbage flavor, carrot flavor, celery flavor, mushroom flavor, and tomato flavor. These flavoring agents may be used in liquid or solid form and may be used individually or mixed. In the context of dairy or dairy-like products, the most commonly used flavoring agents are flavoring agents such as vanilla, French vanilla, chocolate, banana, lemon, hazelnut, coconut, almond, strawberry, mocha, coffee, tea, chai, cinnamon, caramel, cream, brown sugar, toffee, pecan, butter pecan, toffee, Irish cream, white chocolate, raspberry, pumpkin pie spice, peppermint, or any combination thereof.

[0070] In some embodiments, the ingestible composition comprises vanillin or a vanillin analogue, which imparts a vanilla flavor to the flavorant, hi some further embodiments, the ingestible composition comprises one or more lactones, which impart a creamy flavor to the composition.

[0071] In some embodiments, the ingestible composition comprises a yeast extract, such as a yeast lysate. Such an extract can be obtained from any suitable yeast strain, where such an extract is suitable for human consumption. Non-limiting examples of such yeasts include yeasts of the genus Saccharomyces, such as Saccharomyces cerevisiae or Saccharomyces pastorianus; yeasts of the genus Candida, such as Candida utilis; yeasts of the genus Kluyveromyces, such as Kluyveromyces lactis or Kluyveromyces marxianus; yeasts of the genus Pichia, such as Pichia pastoris; yeasts of the genus Debaryomyces, such as Debaryomyces hansenii; and yeasts of the genus Zygosaccharomyces. mellis. In some embodiments, the yeast is a yeast collected after brewing beer, sake, etc. In some embodiments, the yeast is a yeast that has been subjected to a drying process after collection (dried yeast).

[0072] Such extracts can be produced by any suitable means. Generally, yeast extracts or lysates are made by extracting the contents of yeast cells from cell wall material. Often, digestive enzymes in the cells (or additional enzymes added to the composition) break down proteins and polynucleotides in the yeast into amino acids, oligopeptides (e.g., 2-10 peptides), nucleotides, oligonucleotides (2-10 nucleotides) and mixtures thereof. Yeast lysates can be prepared by dissolving yeast. For example, in some embodiments, yeast after culture is disrupted or dissolved by enzymatic degradation, autolysis, alkaline extraction, hot water extraction, acid degradation, ultrasonic disruption, homogenizer disruption, freeze-thawing, or the like (two or more of these may be used in combination) to obtain yeast lysates. Yeast can be cultured by conventional methods. In some embodiments, yeast after culture is heat-treated and then treated with a lytic enzyme to obtain enzymatic lysates. The heat treatment conditions are, for example, 80°C to 90°C for 5 to 30 minutes. As the lytic enzyme used in the enzymatic decomposition method, various enzymes can be used as long as they can dissolve the cell wall of yeast. The reaction conditions may be set to be optimal or suitable for the lytic enzyme used, and specific examples include a temperature of 50°C to 60°C and a pH of 7.0 to 8.0. The reaction time is not particularly limited, and can be, for example, 3 to 5 hours.

[0073] Compositions comprising yeast lysate can be obtained from a variety of commercial sources. For example, in some embodiments, the yeast lysate is provided by a flavor additive sold under the name MODUMAX (DSM Food Specialties BV, Delft, Netherlands).

[0074] In some embodiments, the ingestible composition comprises a sweetness enhancer. Any suitable sweetness enhancer can be used in the ingestible compositions disclosed herein, including synthetic sweetness enhancers, natural sweetness enhancers, or any combination thereof.

[0075] Examples of suitable synthetic sweetener enhancers include, but are not limited to, N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methylpropan-2-yl)isonicotinamide, or any of its edible acceptable salts, 3-hydroxybenzoic acid, or any of the compounds described in U.S. Pat. Nos. 8,541,421, 8,815,956, 9,834,544, 8,592,592, 8,877,922, 9,000,054, and 9,000,051, and U.S. Patent Application Publication No. 2017 / 0119032.

[0076] Suitable examples of natural sweetener enhancers include, but are not limited to, hesperetin dihydrochalcone, hesperetin dihydrochalcone-4'-O' glucoside, neohesperetin dihydrochalcone, brazzein, hesperidin, phyllodulcin, naringenin, naringin, phloretin, glucosylated steviol glycosides, (2R,3R)-3-acetoxy-5,7,4'-trihydroxyflavanone, (2R,3R)-3-acetoxy-5,7,3'-trihydroxy-4'-methoxyflavanone, rubusoside, thaumatin, monellin, miraculin, glycyrrhizin and edible acceptable salts thereof (such as monoammonium salts), naringin dihydrochalcone, myricetin, nobiletin, polymethoxyflavones, mixed methoxy- and hydroxyflavones, quercetin, certain amino acids, and the like. As used herein, the term "glucosylated steviol glycoside" refers to the product of enzymatic glucosylation of a naturally occurring steviol glycoside compound. Glucosylation generally occurs via glycosidic linkages such as α-1,2, α-1,4, α-1.6, β-1,2, β-1,4, and β-1,6 linkages. In some embodiments of any of the preceding embodiments, the ingestible composition comprises 3-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2,2-dimethyl-N-propyl-propanamide, N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]-thiadiazin-5-yl)oxy)-2-methyl-propan-2-yl)isonicotinamide, or a edible acceptable salt thereof. In some embodiments, the ingestible composition comprises N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methyl-propan-2-yl)isonicotinamide or a edible acceptable salt thereof. In some embodiments, the ingestible composition comprises N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methyl-propan-2-yl)isonicotinamide.

[0077] In some embodiments, the ingestible composition comprises one or more umami enhancing compounds. Such umami enhancing compounds include, but are not limited to, naturally occurring compounds or synthetic compounds, such as any of the compounds described in U.S. Patents 8,735,081, 8,124,121, and 8,968,708. In some embodiments, the umami enhancing compound is (2R,4R)-1,2,4-trihydroxy-heptadeca-16-ene, (2R,4R)-1,2,4-trihydroxyheptadeca-16-yne, or a mixture thereof. In some embodiments, the umami enhancing compound is (3R,5S)-1-(4-hydroxy-3-methoxyphenyl)decane-3,5-diol diacetate. In some embodiments, the umami enhancing compound is N-(heptan-4-yl)benzo-[d][1,3]dioxole-5-carboxamide.

[0078] In some further embodiments, the ingestible composition comprises one or more cooling-promoting compounds, including, but not limited to, naturally occurring compounds, such as menthol or analogs thereof, or synthetic compounds, such as any of the compounds described in U.S. Patent Nos. 9,394,287 and 10,421,727. Non-limiting examples include N-ethyl-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide, N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide, 2-(4-fluorophenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide, 2-(2-hydroxy-4-methylphenoxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)acetamide, 2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-( 1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide, 2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiazol-5-ylmethyl)-acetamide, 2-((5-methoxybenzofuran-2-yl)oxy)-N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-acetamide, (E / Z)-2-methyl-2-butenal, (E / Z)-2-isopropyl-5-methyl-2-hexenal, phloretin, naringenin, and any combination thereof.

[0079] In some further embodiments, the ingestible composition comprises one or more bitterness blocking or bitterness masking compounds. Such bitterness blocking or bitterness masking compounds include, but are not limited to, naturally occurring or synthetic compounds, such as any of the compounds described in U.S. Patent Nos. 8,076,491, 8,445,692 and 9,247,759. Non-limiting examples include 3-(1-((3,5-dimethylisoxazol-4-yl)-methyl)-1H-pyrazol-4-yl)-1-(3-hydroxybenzyl)-imidazolidine-2,4-dione, 4-(2,2,3-trimethyl-cyclopentyl)butanoic acid, 3β-hydroxydihydrocostunolide, 3β-hydroxyperenolide, probenecid, sakuranetin, 6-methoxysakuranetin, jaceocidin, 4'-fluoro-6-methoxyflavonone, 6,3'-dimethoxyflavonone, 6-methoxyflavonone, γ-aminobutyric acid, Nα,Nα-bis(carbomethyl)-L-lysine, glycerol, (+ / -) abscisic acid, sodium gluconate, monosodium glutamate, sodium acetate, homoeriodictyol, sterubin, eriodictyol, 2,4,dihydrobenzoic acid, neodiosmin, 1-carboxymethyl-5-hydroxy-2-hydroxymethylpyridinium, flavan-3-spiro-C-glycosides, poly-gamma-glutamic acid, alpha,alpha-trehalose, taurine, (2)-gingerdione, 2,4,dihydroxybenzoic acid, L-theanine, enterodiol, lariciresinol, enterolactone, matairesinol, and any combination thereof.

[0080] In some further embodiments, the ingestible composition comprises one or more acidity regulating compounds.

[0081] In some further embodiments, the ingestible composition comprises one or more texture modifying compounds, including but not limited to tannins, cellulosic materials, bamboo powder, and the like.

[0082] In some further embodiments, the ingestible composition comprises one or more flavor-masking compounds, including, but not limited to, cellulosic materials, materials extracted from fungi, materials extracted from plants, citric acid, carbonic acid (or carbonates), and the like.

[0083] Flavoured products In certain aspects, the present disclosure provides a flavored product comprising any of the ingestible compositions of the aforementioned aspects. In some embodiments, the flavored product is a beverage product, such as soda, flavored water, tea, etc. In some other embodiments, the flavored product is a food product, such as yogurt. In some embodiments, the flavored product is an oral care product, such as toothpaste, mouthwash, dentifrices, whitening agents, etc.

[0084] In embodiments where the flavored product is a beverage, the beverage may be selected from the group consisting of enhanced sparkling beverages, cola, lemon-lime flavored sparkling beverages, orange flavored sparkling beverages, grape flavored sparkling beverages, strawberry flavored sparkling beverages, pineapple flavored sparkling beverages, ginger ale, root beer, fruit juice, fruit flavored juice, juice drink, nectar, vegetable juice, vegetable flavored juice, sports drink, energy drink, enhanced water drink, enhanced water with vitamins, near water drink, coconut water, tea-based drink, coffee, cocoa drink, beverages containing dairy ingredients, beverages containing cereal extracts, and smoothies. In some embodiments, the beverage may be a soft drink.

[0085] In certain embodiments of any of the aspects and embodiments described herein that refer to a flavored product, the flavored product is a non-naturally occurring product, such as a packaged food or beverage product.

[0086] Further non-limiting examples of food and beverage products or formulations include sweet coatings, frostings, or glazes for such products or any articles included in the soup category, the dried prepared foods category, the beverage category, the ready meal category, the canned or preserved foods category, the frozen prepared foods category, the chilled prepared foods category, the snack foods category, the baked goods category, the confectionery category, the dairy category, the ice cream category, the meal replacements category, the pasta and noodles category, and the sauces, dressings, condiments category, the baby food category, and / or the spreads category.

[0087] In general, the soup category refers to canned / preserved, dehydrated, instant, chilled, UHT and frozen soups. For the purposes of this definition, soup means food prepared from meat, poultry, fish, vegetables, grains, fruits and other ingredients, cooked in a liquid that may contain some or all visible portions of these ingredients. Soups may be clear (as broths) or thick (as chowders), smooth, pureed or chunky, ready to serve, semi-condensed or condensed, and may be served hot or cold, as a first course or as the main course of a meal, or as a snack between meals (sipped in small portions like a beverage). Soups may be used as an ingredient for cooking other meal components and may range from broths (consomme) to sauces (cream or cheese-based soups).

[0088] The dehydrated and prepared foods category generally refers to: (i) cooking aid products, such as powders, granules, pastes, concentrated liquid products, such as concentrated bouillons, bouillons and bouillon-like products in compressed cubes, tablets, powders or granules form, sold separately (regardless of technology) as finished products or as ingredients in products, sauces and recipe mixes; (ii) dietary solution products, such as dehydrated and freeze-dried soups, such as dehydrated soup mixes, dehydrated instant soups, dehydrated semi-cooked soups, dehydrated or packaged ready-made staples and single-serving main dishes including pasta, potato and rice dishes; (iii) meal accompaniment products, such as condiments, marinades, salad dressings, salad toppings, dips, bread crumbs, batter mixes, shelf stable spreads, barbecue sauces, liquid recipe mixes, concentrates, sauces or sauce mixes, such as salad recipe mixes, sold in dehydrated, liquid or frozen state, either as finished products or as ingredients in products.

[0089] The beverage category generally refers to beverages, beverage mixes and concentrates, including but not limited to carbonated and non-carbonated beverages, alcoholic and non-alcoholic beverages, ready-to-drink beverages, liquid concentrate formulations for producing beverages such as sodas, and dry powdered beverage pre-mixes. The beverage category also includes alcoholic drinks, soft drinks, sports drinks, isotonic drinks and hot drinks. Alcoholic drinks include but are not limited to beer, cider / perry, FAB, wine and spirits. Soft drinks include carbonated, e.g. cola and non-cola carbonated; fruit juices, e.g. juice, nectar, juice drinks and fruit flavored drinks; bottled water, e.g. sparkling water, spring water and purified water / table water; functional drinks, e.g. which may be carbonated or non-carbonated and include sports drinks, energy drinks or elixir drinks; concentrates, e.g. ready-to-drink measured liquid and powder concentrates. Hot or cold drinks include, but are not limited to, coffee or iced coffee, such as brewed, instant and combination coffees; tea or iced tea, such as black tea, green tea, white tea, oolong tea and flavored teas; and other beverages, including flavored, malt or plant-based powders, granules, blocks or tablets mixed with milk or water.

[0090] The snack food category generally refers to any food that can be a light informal meal, including but not limited to sweet and savory snacks and snack bars. Examples of snack foods include, but are not limited to, fruit snacks, chips / crisps, extruded snacks, tortilla / corn chips, popcorn, pretzels, nuts, and other sweet and savory snacks. Examples of snack bars include, but are not limited to, granola / muesli bars, breakfast bars, energy bars, fruit bars, and other snack bars.

[0091] The baked goods category generally refers to any edible product whose preparation method involves exposure to heat or excessive sunlight. Examples of baked goods include, but are not limited to, bread, buns, cookies, muffins, cereals, toaster pastries, pastries, waffles, tortillas, biscuits, pies, bagels, tarts, quiches, cakes, any baked food product, and any combination thereof.

[0092] The ice cream category generally refers to frozen desserts that contain cream and sugar and flavorings. Examples of ice cream include, but are not limited to, impulse ice cream; take-home ice cream; frozen yogurt and artisanal ice cream; soy, oat, bean (e.g., red bean and mung bean) and rice-based ice cream.

[0093] The confectionery category generally refers to sweet tasting edible products. Examples of confectionery include, but are not limited to, candy, gelatin, chocolate confectionery, sugar confectionery, gum, and the like, and any combination products.

[0094] The meal replacement category generally refers to any food product intended to replace a regular meal, especially for people with health or fitness concerns. Examples of meal replacements include, but are not limited to, slimming products and recovery products.

[0095] The ready meal category generally refers to any food that can be served as a meal without extensive cooking or processing. Ready meals include products to which recipe "skill" has been added by the manufacturer, resulting in a high degree of preparation, completion and convenience. Examples of ready meals include, but are not limited to, canned / preserved, frozen, dried, chilled ready meals; dinner mixes; frozen pizza; chilled pizza; and pre-prepared salads.

[0096] The pasta and noodles category includes any pasta and / or noodles, including but not limited to canned, dried and chilled / fresh pasta; regular, instant, chilled, frozen and snack noodles.

[0097] The canned / preserved foods category includes, but is not limited to, canned / preserved meat and meat products, fish / seafood, vegetables, tomatoes, beans, fruit, ready meals, soups, pasta and other canned / preserved foods.

[0098] The frozen processed foods category includes, but is not limited to, frozen processed red meat, processed poultry, processed fish / seafood, processed vegetables, meat substitutes, processed potatoes, bakery products, desserts, ready meals, pizza, soups, noodles and other frozen foods.

[0099] The dry processed food category includes, but is not limited to, rice, dessert mixes, dry ready meals, dehydrated soups, instant soups, dry pasta, regular noodles and instant noodles. The chilled processed food category includes, but is not limited to, chilled processed meats, processed fish / seafood products, lunch kits, fresh cut fruit, ready meals, pizza, prepared salads, soups, fresh pasta and noodles.

[0100] The sauces, dressings and condiments category includes, but is not limited to, tomato paste and purees, bouillon / stock cubes, herbs and spices, monosodium glutamate (MSG), table sauces, soy-based sauces, pasta sauces, wet / cooking sauces, dry sauces / powder mixes, ketchup, mayonnaise, mustard, salad dressings, vinaigrettes, dips, pickle products and other sauces, dressings and condiments.

[0101] Baby food categories include, but are not limited to, milk or soy-based formulas; cooked, dried and other baby foods.

[0102] Spread categories include, but are not limited to, jams and preserves, honey, chocolate spreads, nut-based spreads and yeast-based spreads.

[0103] The dairy category generally refers to edible products produced from mammalian milk. Examples of dairy products include, but are not limited to, drinking milk products, cheese, yogurt and sour milk drinks, and other dairy products.

[0104] Additional examples of flavored products, particularly food and beverage products or formulations, are provided below. Exemplary ingestible compositions include one or more of confectionery, chocolate confectionery, tablets, countlines, bagged selflines / softlines, boxed assortments, standard boxed assortments, twist wrapped miniatures, and the like. miniatures, seasonal chocolates, chocolates with toys, alfajores, other chocolate confectionery, mints, standard mints, power mints, boiled sweets, pastilles, gums, jellies and chews, toffees, caramel and nougat, medicated confectionery, lollipops, liquorice, other sugar confectionery, bread, packaged / industrial bread, unpackaged / artisan bread, pastries, cakes, packaged / industrial cakes, unpackaged / artisan cakes, cookies, chocolate coated biscuits, sandwich biscuits, filled biscuits, savoury biscuits and crackers, bread substitutes, breakfast cereals, rte cereals, family breakfast cereals, flakes, muesli, other cereals, children's breakfast cereals, hot cereals, ice cream, impulse ice cream, single portion dairy ice cream, single portion water ice cream, multi-pack dairy ice cream, marmalade Chipac water ice cream, take away ice cream, take away dairy ice cream, ice cream desserts, bulk ice cream, take away water ice cream, frozen yogurt, artisanal ice cream, dairy products, milk, raw milk / pasteurized milk, full fat raw milk / pasteurized milk, semi skimmed milk / pasteurized milk, long life / uht milk, full fat long life / uht milk, semi skimmed long life / uht milk, non fat long life / uht milk, goat milk, condensed milk / evaporated milk, plain condensed milk / evaporated milk, flavoured, functional and other condensed milk, flavoured milk drinks, dairy only flavoured milk drinks, flavoured dairy drinks with fruit juice, soy milk, sour milk drinks, fermented dairy drinks, coffee whitener, milk powder, flavoured milk powder drinks, cream, cheese, processed cheese, spreadable processed cheese, non spreadable processed cheese, raw cheese, spreadable raw cheese,Hard Cheese, Packaged Hard Cheese, Unpackaged Hard Cheese, Yogurt, Plain Yogurt / Natural Yogurt, Flavoured Yogurt, Fruit Yogurt, Probiotic Yogurt, Drinking Yogurt, Regular Drinking Yogurt, Probiotic Drinking Yogurt, Refrigerated Shelf Stable Desserts, Dairy Based Desserts, Soy Based Desserts, Chilled Snacks, Fromage Frais and Quark, Plain Fromage Frais and Quark, Flavoured Fromage Frais and Quark, Savory Fromage Frais and Quark, Sweet and Savory Snacks, Fruit Snacks, Chips / Crisps, Extruded Snacks, Tortilla / Corn Chips, Popcorn, Pretzels, Nuts, Other Sweet and Savory Snacks, Snack Bars, Granola Bars, Breakfast Bars, Energy Bars, Fruit Bars, Other Snack Bars, Meal Replacement Products, Slimming Products, Recovery Drinks, Ready Meals, Canned Ready Meals, Frozen Ready Meals, Dried Ready Meals, Chilled Ready Meals, Dinner Mixes, Frozen Pizza, Chilled Pizza, Soups, Canned Soups, Dehydrated Soups, Instant Soups, Chilled soup, Hot soup, Frozen soup, Pasta, Canned pasta, Dried pasta, Chilled / fresh pasta, Noodles, Regular noodles, Instant noodles, Cup / bowl instant noodles, Pouch instant noodles, Chilled noodles, Snack noodles, Canned food, Canned meat and meat products, Canned fish / seafood, Canned vegetables, Canned tomatoes, Canned beans, Canned fruit, Canned ready meals, Canned soup, Canned pasta, Other canned food, Frozen food, Frozen processed red meat, Frozen processed poultry, Frozen processed fish / seafood, Frozen processed vegetables, Frozen meat substitutes, Frozen potatoes, Oven baked potato chips, Other oven baked potato products, Oven Frozen Potatoes, Frozen Bakery Products, Frozen Desserts, Frozen Ready Meals, Frozen Pizza, Frozen Soups, Frozen Noodles, Other Frozen Foods, Dehydrated Foods, Dessert Mixes, Dehydrated Ready Meals, Dehydrated Soups, Instant Soups, Dehydrated Pasta, Plain Noodles, Instant Noodles, Cup / Bowl Instant Noodles, Pouch Instant Noodles, Chilled Foods, Chilled Processed Meat, Chilled Fish / Seafood Products, Chilled Processed Fish, Chilled Coated Fish, Chilled Smoked Fish, Chilled Lunch Kits, Chilled Ready Meals, Chilled Pizza, Chilled Soups, Chilled / Fresh Pasta, Chilled Noodles, Oils and Fats, Olive Oil, Vegetable Seed Oil,cooking fats and oils, butter, margarine, spreadable fats and oils, functional spreadable fats and oils, sauces, dressings and condiments, tomato paste and puree, bouillon / stock cubes, stock cubes, gravy granules, liquid stocks and fonds, herbs and spices, fermented sauces, soy based sauces, pasta sauces, wet sauces, dry sauces / powder mixes, ketchup, mayonnaise, regular mayonnaise, mustard, salad dressings, regular salad dressings, low fat salad dressings, vinaigrettes, dips, pickle products, other sauces, dressings and condiments, baby food, formulas, standard formulas, follow-on formulas, toddler formulas, hypoallergenic formulas, prepared baby foods, dry baby foods, other baby foods, spreads, jams and preserves, honey, chocolate spreads, nut based spreads, and yeast based spreads. Exemplary ingestible compositions include confectionery, bakery products, ice cream, dairy products, sweet and savory snacks, snack bars, meal replacement products, ready meals, soups, pastas, noodles, canned foods, frozen foods, dry foods, chilled foods, fats and oils, baby foods or spreads, or mixtures thereof. Exemplary ingestible compositions also include solid or liquid concentrate compositions for producing breakfast cereals, sweetened beverages, or beverages, ideally allowing for the reduction of the concentration of previously known sugar sweeteners or artificial sweeteners.

[0105] Some embodiments provide chewable compositions that may or may not be intended to be swallowed. In some embodiments, the chewable compositions may be gums, chewing gums, sugar gums, sugarless gums, functional gums, bubble gums, containing the compounds disclosed and described herein, individually or in combination.

[0106] Typically, at least a sweet receptor modulating amount, a sweet receptor ligand modulating amount, a sweet flavor modulating amount, a sweet flavor agent amount, a sweet flavor enhancing amount, or a therapeutically effective amount of one or more of the present compounds, optionally in the presence of a sweetener, is added to an ingestible composition such that the sweet flavor modified ingestible composition has increased sweetness compared to an ingestible composition prepared without the compounds of the present invention, as judged generally by a human or animal, or in the case of formulation testing, by a majority of a panel of at least eight human taste testers, via procedures commonly known in the art.

[0107] In some embodiments, the compounds disclosed and described herein, individually or in combination, modulate the sweetness or other taste characteristics of other natural or synthetic sweeteners and ingestible compositions made therefrom. In one embodiment, the compounds disclosed and described herein, individually or in combination, can be used or provided at their ligand-enhanced concentrations. For example, the compounds disclosed and described herein, individually or in combination, can be present in amounts of 0.001 ppm to 100 ppm, or 0.1 ppm to 50 ppm, 0.01 ppm to 40 ppm, 0.05 ppm to 30 ppm, 0.01 ppm to 25 ppm, or 0.1 ppm to 30 ppm, or 0.1 ppm to 25 ppm, or 1 ppm to 30 ppm, or 1 ppm to 25 ppm, or narrower alternative ranges.

[0108] In some embodiments, the ingestible compositions disclosed herein may be provided individually or in combination, for example, in a flavor concentrate formulation suitable for subsequent processing to produce a ready-to-use (i.e., ready-to-serve) product. A "flavor concentrate formulation" refers to a formulation to be reconstituted with one or more dilution media to become a ready-to-use composition. The term "ready-to-use composition" is used interchangeably herein with "ingestible composition", which refers to any substance that can be taken by mouth, whether or not it is intended for consumption, alone or together with another substance. In one embodiment, a ready-to-use composition includes a composition that can be directly consumed by a human or animal. A flavor concentrate formulation is typically used by mixing with or diluting with one or more dilution media, e.g., any consumable or ingestible ingredient or product, to impart or modify one or more flavors to the dilution medium. Such a method of use is often referred to as reconstitution. Reconstitution can be performed in a domestic or industrial environment. For example, a frozen fruit juice concentrate can be reconstituted with water or other aqueous medium by a consumer in the kitchen to obtain a ready-to-use fruit juice beverage. In another example, soft drink syrup concentrates can be reconstituted with water or other aqueous media by manufacturers on a large industrial scale to produce ready-to-use soft drinks. Because flavor concentrate formulations have higher concentrations of flavoring agents or flavor modifiers than ready-to-use compositions, flavor concentrate formulations are typically not suitable for direct consumption without reconstitution. There are many benefits to the use and manufacture of flavor concentrate formulations. For example, one benefit is that flavor concentrate formulations can be reconstituted at the time of use by adding a suitable solvent, solid or liquid, thus reducing the weight and volume of shipping.

[0109] The flavored products according to any of the foregoing embodiments also, in certain embodiments, comprise one or more additional flavor modifying compounds, such as a compound that enhances sweetness (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), a compound that blocks bitterness, a compound that enhances umami, a compound that reduces sourness, a compound that enhances saltiness, a compound that enhances cooling effect, or any combination of the foregoing.

[0110] In certain embodiments of any of the aspects and embodiments described herein that refer to a sweetening or flavoring concentrate, the sweetening or flavoring concentrate is a composition that is specially manufactured for the production of a non-naturally occurring product, e.g., a flavored product, such as a food or beverage product.

[0111] In one embodiment, the flavor concentrate formulation comprises i) the compound disclosed and described herein, either individually or in combination, ii) a carrier, and iii) optionally at least one adjuvant. The term "carrier" refers to a normally inert accessory substance, such as a solvent, binder, or other inert vehicle, that is used in combination with the compound and one or more optional adjuvants to form a formulation. For example, water or starch can be a carrier for the flavor concentrate formulation. In some embodiments, the carrier is the same as the dilution medium for reconstituting the flavor concentrate formulation, and in other embodiments, the carrier is different from the dilution medium. The term "carrier" as used herein includes, but is not limited to, ingestibly acceptable carriers.

[0112] The term "adjuvant" refers to an additive that supplements, stabilizes, maintains or enhances the intended function or effectiveness of an active ingredient, such as a compound of the present invention. In one embodiment, the at least one adjuvant includes one or more flavoring agents. The flavoring agents may be of any flavor known to the artisan or consumer, such as the flavors of chocolate, coffee, tea, mocha, French vanilla, peanut butter, chai, or combinations thereof. In another embodiment, the at least one adjuvant includes one or more sweeteners. The one or more sweeteners may be any of the sweeteners described in this application. In another embodiment, the at least one adjuvant includes one or more ingredients selected from the group consisting of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, salts, and combinations thereof. Examples of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, and salts are described in U.S. Pat. No. 6,468,576, the contents of which are incorporated herein by reference in their entirety for all purposes.

[0113] In one embodiment, the flavor concentrate formulation may be in a form selected from the group consisting of liquids, including solutions and suspensions, solids, foams, pastes, gels, creams, and combinations thereof, such as liquids containing a certain amount of solids. In one embodiment, the flavor concentrate formulation is in the form of a liquid, including aqueous and non-aqueous. In some embodiments, the flavor concentrate formulation may be carbonated or non-carbonated.

[0114] The flavor concentrate formulation may further include a freezing point depressant, a nucleating agent, or both as at least one adjuvant. A freezing point depressant is a ingestibly acceptable compound or agent that can depress the freezing point of a liquid or solvent to which the compound or agent is added. That is, a liquid or solution containing a freezing point depressant has a lower freezing point than a liquid or solvent without the freezing point depressant. In addition to depressing the starting freezing point, the freezing point depressant can also reduce the water activity of the flavor concentrate formulation. Examples of freezing point depressants include, but are not limited to, carbohydrates, oils, ethyl alcohol, polyols such as glycerol, and combinations thereof. A nucleating agent refers to a ingestibly acceptable compound or agent that can promote nucleation. The presence of a nucleating agent in the flavor concentrate formulation can improve the texture of the frozen blushes of the frozen slush and help maintain the physical properties and performance of the slush at freezing temperatures by increasing the number of desirable ice crystallization centers. Examples of nucleating agents include, but are not limited to, calcium silicate, calcium carbonate, titanium dioxide, and combinations thereof.

[0115] In one embodiment, the flavor concentrate formulation is formulated to have a low water activity to extend shelf life. Water activity is the ratio of the vapor pressure of water in the formulation to the vapor pressure of pure water at the same temperature. In one embodiment, the flavor concentrate formulation has a water activity of less than about 0.85. In another embodiment, the flavor concentrate formulation has a water activity of less than about 0.80. In another embodiment, the flavor concentrate formulation has a water activity of less than about 0.75.

[0116] In one embodiment, the flavor concentrate formulation has the compound at a concentration at least twice as high as the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration at least 5 times as high as the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration at least 10 times as high as the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration at least 15 times as high as the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration at least 20 times as high as the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration at least 30 times as high as the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration at least 40 times as high as the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration at least 50 times as high as the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of at least 60 times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has the compound at a concentration of up to 100 times the concentration of the compound in the ready-to-use composition.

[0117] In some embodiments, flavorants can be used in many different physical forms known in the art to provide an initial burst of flavor and / or a long-term sensation of flavor, including, but not limited to, free forms such as spray-dried forms, powdered forms, beaded forms, encapsulated forms, and mixtures thereof.

[0118] In some embodiments, the ingestible composition comprises a flavor modifying compound according to any of the above embodiments and a bulking agent. Suitable bulking agents include, but are not limited to, maltodextrin (10 DE, 18 DE, or 5 DE), corn syrup solids (20 or 36 DE), sucrose, fructose, glucose, invert sugar, sorbitol, xylose, ribulose, mannose, xylitol, mannitol, galactitol, erythritol, maltitol, lactitol, isomalt, maltose, tagatose, lactose, inulin, glycerol, propylene glycol, polyols, polydextrose, fructooligosaccharides, cellulose and cellulose derivatives, and the like, and mixtures thereof. In addition, granulated sugar (sucrose) or other caloric sweeteners such as crystalline fructose, other carbohydrates, or sugar alcohols can be used as bulking agents, since they provide good content uniformity without adding significant calories.

[0119] In one embodiment, the at least one bulking agent may be a bulking agent described in US Pat. No. 8,993,027.

[0120] In one embodiment, the at least one bulking agent may be a bulking agent described in US Pat. No. 6,607,771.

[0121] In one embodiment, the at least one bulking agent may be a bulking agent described in US Pat. No. 6,932,982.

[0122] In some embodiments, the tabletop sweetener composition may further comprise at least one anti-caking agent. As used herein, the phrases "anti-caking agent" and "flow agent" refer to any composition that prevents, reduces, inhibits, or inhibits at least one sweetener from attaching to, binding to, or contacting another sweetener molecule. Alternatively, an anti-caking agent can refer to any composition that aids in content uniformity and uniform dissolution. Non-limiting examples of anti-caking agents include cream of tartaric acid, calcium silicate, silicon dioxide, microcrystalline cellulose (Avicel, FMC BioPolymer, Philadelphia, PA), and tricalcium phosphate. In one embodiment, the anti-caking agent is present in the tabletop sweetener composition in an amount of about 0.001 to about 3% (by weight) of the tabletop sweetener composition.

[0123] In some embodiments, the sweetener composition of any of the foregoing aspects and embodiments thereof is encapsulated using typical means for encapsulating flavor or aroma compounds. Non-limiting examples of such techniques include U.S. Patent Application Publication Nos. 2016 / 0235102, 2019 / 0082727, 2018 / 0369777, 2018 / 0103667, 2016 / 0346752, 2015 / 0164117, 2014 / 0056836, 2012 / 0027866, 2010 / 0172945, and the like. and 2007 / 0128234, as well as U.S. Patent Nos. 7,488,503, 6,416,799, 5,897,897, 5,786,017, 5,603,971, 4,689,235, 4,610,890, 3,704,137, 3,041,180, and 2,809,895. All of the foregoing patent publications and patents are incorporated herein by reference as if set forth in their entireties herein.

[0124] Non-animal protein materials and products made therefrom Products intended to replace or substitute meat or dairy products often rely on various non-animal-based materials, such as starch, fiber and protein derived from plants, algae, fungi or combinations thereof, to mimic the texture and flavor of meat or dairy products.Non-limiting examples of non-animal-based proteins include vegetable proteins, such as pea protein, soy protein, almond protein, cashew protein, canola (rapeseed) protein, chickpea protein, broad bean protein, sunflower protein, wheat protein, oat protein, barley protein and potato protein, and combinations thereof.Due to the compositional differences between such plant-based materials and animal-based materials, such as the lack of glutamic acid-containing proteins and glutathione, these products may lack the umami or kokumi flavor that consumers traditionally associate with meat or dairy products, or may have a bitter taste that animal proteins lack.

[0125] Thus, in certain aspects, the present disclosure provides a flavored product comprising a plant-based material (e.g., a plant-based starch, a plant-based protein, or a combination thereof) and a zinc salt according to any of the above embodiments. In some further embodiments, the flavored product can include any of the combinations of features described above for ingestible compositions containing zinc salts. In some embodiments, the flavored product is a beverage, such as soy milk, almond milk, rice milk, oat milk, a protein drink, a meal replacement drink, or other similar products. In some other embodiments, the flavored product is a meat replacement product, such as a plant-based chicken product (e.g., a plant-based chicken nugget), a plant-based beef product (e.g., a plant-based burger), or the like. In some other embodiments, the flavored product is a protein powder, a meal replacement powder, a plant-based creamer for coffee or tea, and the like. In certain further embodiments, any such product contains additional ingredients and has additional features typically used in the preparation and / or manufacture of such products. For example, the flavor-modifying compound may be combined with other flavorings and taste modifiers, or even encapsulated in a particular material, according to known techniques in the relevant art. Suitable concentrations of the flavour modifying compounds are given above.

[0126] In some embodiments, the flavored product comprises one or more plant-based proteins that impart a bitter taste that is at least partially reduced by the use of flavor modifying compounds in the product. Such plant-based proteins include, but are not limited to, pea protein, soy protein, almond protein, cashew protein, canola (rapeseed) protein, chickpea protein, broad bean protein, sunflower protein, wheat protein, oat protein, barley protein and potato protein, and combinations thereof.

[0127] In some alternative embodiments similar to those described above, algae or fungal proteins or starches are used instead. In some embodiments, these flavored products also contain fiber to provide texture to the product. Fibers suitable for use include, but are not limited to, psyllium fiber, pea fiber, potato fiber, curdlan, soluble corn fiber (dextran and / or maltodextrin), citrus fiber, and combinations thereof. In such products, the flavor-modifying compound can be introduced in any suitable manner. In some embodiments, the flavor-modifying compound is incorporated into a flavored emulsion, such as a water-in-oil emulsion, along with other flavor-imparting ingredients.

[0128] Non-meat protein materials and products made therefrom Certain non-meat animal proteins, such as dairy proteins and proteins from bone broth, are commonly used in foods and are also sold as the main ingredient of certain protein powders. Such proteins can impart a bitter taste that consumers may not want. This is particularly true for protein isolates, such as whey protein, collagen protein, casein protein, and other protein isolates. Thus, the present disclosure provides ingestible compositions that include non-meat animal proteins and flavor-modifying compounds. The flavor-modifying compounds can be present in any suitable combination according to the embodiments described in the preceding sections of the present disclosure. In some embodiments, the non-meat animal protein is a bone protein, such as collagen protein, derived from the bones of animals, such as cows, pigs, donkeys, horses, chickens, ducks, goats, geese, rabbits, lambs, sheep, buffalo, ostriches, camels, and the like. In some embodiments, the non-meat animal protein is a milk protein, such as whey protein, casein protein, or any combination thereof. The milk can be the milk of any suitable animal, such as cows, donkeys, horses, sheep, buffalo, camels, and the like.

[0129] The flavor modifying compounds may also be included in certain food or beverage products that contain animal milk or ingredients derived from animal milk, such as cheese, cheese spreads, yogurt, kefir, milk, processed dairy products, cottage cheese, sour cream, butter, etc.

[0130] Blocking bitterness in pharmaceutical APIs Many drug compounds impart a bitter taste, which therefore limits the way in which they can be formulated and administered. Thus, in certain aspects, the present disclosure provides a pharmaceutical composition comprising a bitter tasting pharmacoactive ingredient and a taste-modifying compound. Such pharmaceutical compositions can be in any suitable form for oral administration, such as tablets, lozenges, capsules, powders, liquid solutions, liquid suspensions, etc. Such pharmaceutical compositions can include any suitable pharmaceutical excipients, binders, etc., such as those described in Remington's Pharmaceutical Sciences. In some embodiments, the bitter tasting pharmacoactive ingredient is an ion channel inhibitor, e.g., a proton channel inhibitor. Other examples of bitter tasting APIs whose bitterness is reduced by the taste-modifying compounds include, but are not limited to, atropine, brinzolamide, chloramphenicol, chloroquine, clindamycin, dexamethasone, digoxin, diltiazem, diphenhydramine, docusate, dorzolamide, doxepin, doxylamine, enalapril, erythromycin, esomeprazole, famotidine, gabapentin, ginkgolide A, guaifenesin, L-histidine, lomefloxacin, methylprednisolone, ofloxacin, oleuropein, oxyphenonium, pirenzepine, prednisone, ranitidine, trapidil, trimethoprim, and cetirizine.

[0131] Use in oral care products Oral care products often contain ingredients that give an astringent or bitter taste. Such ingredients include menthol, menthol analogs, mint extracts, sodium bicarbonate, alkali metal salts of peroxymonosulfate (potassium peroxymonosulfate), cetylpyridinium chloride, lauramidopropyl betaine, cocamidopropyl betaine, arginine, hydrogen peroxide, chlorhexidine gluconate, potassium nitrate, pentasodium triphosphate, tetrasodium pyrophosphate, stannous fluoride, thymol, methyl salicylate, eucalyptol, or any combination thereof. Suitable oral care products include toothpaste, mouthwash, whitening agents, dentifrices, etc. Such oral care products may include flavor modifying compounds to block or mask the bitter taste of such compounds. EXAMPLES

[0132] The following examples are included to further illustrate the present invention. Of course, the examples should not be construed as specifically limiting the present invention. Variations of these examples within the scope of the claims are within the scope of those skilled in the art and are considered to be within the scope of the invention described and claimed herein. The reader will recognize that the skilled and skilled artisan given this disclosure can prepare and use the present invention without exhaustive examples.

[0133] Example 1: Preparation of (trans)-5,7-dihydroxy-2-(4-hydroxyphenyl)-3-methoxychroman-4-one (101) [ka] A 250 mL round bottom flask equipped with a stir bar was charged with A-1 (Example 1a, 350 mg, 0.81 mmol) and MeOH (50 mL) followed by HCl (12N, 18 mL). The resulting solution was stirred at 22° C. for 90 min after which LCMS analysis indicated consumption of starting material. The solvent was removed under reduced pressure and the residue was dissolved in MeOH (20 mL) and the solvent was removed under reduced pressure. The crude residue was purified by preparative RP HPLC (10→90% MeCN / H2O) and the purified material was lyophilized from an EtOH-H2O mixture to give 207 mg (85% yield) of the desired compound 101 as a white solid. 1 H NMR(500 MHz,MeOD)δ 7.46-7.26(m,2H),6.93-6.75(m,2H),5.91(d,J=2.1 Hz,1H),5.87(d,J=2.2 Hz,1H),5.08(d,J=10.5 Hz,1H),4.26(d,J=10.5 Hz,1H),3.34(s,3H).C 16 H 15 O2[M+H] + MS(ESI) calculated for 303.1, found 303.0.

[0134] Example 1a: Preparation of (trans)-3-methoxy-5,7-bis(methoxymethoxy)-2-(4-(methoxymethoxy)phenyl)chroman-4-one (A-1) [ka] An oven-dried 40 mL vial equipped with a stir bar and Teflon cap was charged with A-2 (Example 1b, 460 mg, 1.1 mmol) and Ag2O (1.0 g, 4.4 mmol) followed by MeI (6 mL) under N2. The suspension was heated to 45 °C with vigorous stirring for 5 days, after which LCMS analysis showed approximately 80% conversion. The suspension was diluted with DCM (25 mL) and filtered through Celite. The filter cake was washed with additional DCM (2 x 50 mL) and the combined filtrates were concentrated under reduced pressure. The crude residue was purified by preparative RP HPLC (45 -> 80% MeCN / H2O) to give 350 mg (74% yield, 82% (46 mg) based on recovered starting material) of MOM-protected 3-OMe-flavanonol A-1 as a clear oil. 1 H NMR(400 MHz,CDCl3)δ 7.47(d,J=8.5 Hz,2H),7.10(d,J=8.5 Hz,2H),6.45(d,J=1.8 Hz,1H),6.34(d,J=1.8 Hz,1H),5.37-5.24(m,2H),5.20(s,2H),5.16(s,2H),4.99(d,J=12.2 Hz,1H),4.44(dd,J=12.2,1.9 Hz,1H),4.01(d,J=2.1 Hz,1H),3.53(d,J=1.4 Hz,3H),3.47(s,3H),3.46(s,3H);C 22 H 27 O9[M+H] + MS(ESI) calculated for 435.2, found 435.2.

[0135] Example 1b. Preparation of (trans)-3-hydroxy-5,7-bis(methoxymethoxy)-2-(4-(methoxymethoxy)phenyl)chroman-4-one (A-2) [ka] To an ice-cold (ice bath) solution of A-3 (Example 1c, 3.7 g, 9.2 mmol) in dioxane (100 mL) was added Et2NH (4.7 mL, 46 mmol) under N2, followed by slow addition of H2O2 (30% wt, 113 mL, 915 mmol) over 15 min. The reaction mixture was left stirring for 2 h (allowing the ice bath to melt) and then left at 0 °C (refrigerator) for 17 h, after which LCMS analysis indicated consumption of starting material. The mixture was diluted with H2O (500 mL) and extracted (3 x 300 mL EtOAc). The organic layers were combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (25 -> 55% EtOAc / Hexanes) to give 460 mg (12% yield) of the title compound A-2 as a pale yellow oil that turned to a white solid on standing. 1 H NMR(400 MHz,MeOD)δ 7.46(d,J=8.2 Hz,2H),7.08(d,J=8.6 Hz,2H),6.48(d,J=2.3 Hz,1H),6.31(d,J=2.3 C 21 H 25 O9[M+H] + MS(ESI) calculated for 421.2, found 421.0.

[0136] Example 1c: Preparation of (E)-1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)-3-(4-(methoxymethoxy)phenyl)prop-2-en-1-one (A-3) [ka] To a solution of A-4 (Example 1d, 2.95 g, 11.5 mmol) in ethanol (45 mL) was added aqueous KOH (50% wt, 18 mL, 160 mmol) at 0° C. After stirring for 30 min, A-6 (Example 1e, 2.1 g, 13 mmol) in EtOH (5 mL) was added dropwise. The reaction mixture was left stirring for 20 h on a slowly melting ice bath. LCMS analysis showed consumption of starting material. The mixture was diluted with Et2O (125 mL) and washed with saturated aqueous NH4Cl (2×100 mL). The aqueous layers were combined and extracted with (2×125 mL Et2O). The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0→65% EtOAc / Hexanes) to give 3.7 g (79% yield) of chalcone A-3 as a yellow oil. 1 H NMR(400 MHz,CDCl3)δ 7.88-7.73(m,2H),7.55(d,J=8.8 Hz,2H),7.07(d,J=8.6 Hz,2H),6.32(d,J=2.3 Hz,1H),6.25(d,J=2.5 C 21 H 25 O8[M+H] + MS(ESI) calculated for 405.2, found 405.0.

[0137] Example 1d: Preparation of 1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)ethan-1-one (A-4) [ka] A 500 mL oven-dried round-bottom flask equipped with a stir bar and rubber septum was charged with 2,4,6-trihydroxyacetophenone A-5 (3.8 g, 23 mmol) followed by dry DCM (100 mL) under N2. The mixture was cooled to 0 °C in an ice bath and DIPEA (11 mL, 63 mmol) was added slowly. After stirring for 20 min, MOMCl (3.8 mL, 50 mmol) was added dropwise to the suspension at 0 °C over 15 min. The reaction was left stirring for 4 h (the ice bath was allowed to melt and the suspension became a light brown solution), after which LCMS analysis indicated consumption of starting material. Water (100 mL) was added followed by extraction with DCM (3 x 75 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0→100% EtOAc / hexanes) to afford 3.0 g (51% yield) of acetophenone A-4 as a clear oil that solidified upon standing. 1 H NMR(400 MHz,DMSO-d6)δ 13.34(s,1H),6.23(d,J=2.3 Hz,1H),6.19(d,J=2.3 Hz,1H),5.30(s,2H),5.23(s,2H),3.44(s,3H),3.38(s,3H),2.60(s,3H);C 12 H 17 O6 [M+H] + MS(ESI) calculated for 257.1, found 257.2.

[0138] Example 1e: Preparation of 4-(methoxymethoxy)benzaldehyde (A-6) [ka] A 1 L oven-dried round-bottom flask equipped with a stir bar and rubber septum was charged with 4-hydroxybenzaldehyde A-7 (12 g, 98 mmol) followed by dry DCM (250 mL) under N2. The mixture was cooled to 0 °C in an ice bath and DIPEA (24 mL, 140 mmol) was added slowly. After stirring for 20 min, MOMCl (8.2 mL, 110 mmol) was added dropwise to the suspension at 0 °C over 15 min. The reaction was left stirring for 18 h (allowing the ice bath to melt) after which LCMS analysis indicated consumption of starting material. Water (250 mL) was added followed by extraction with DCM (3 x 150 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0→50% EtOAc / hexanes) to afford 15.7 g (96% yield) of aldehyde A-6 as a clear oil. 1 H NMR(400 MHz,CDCl3)δ 9.90(s,1H),7.83(d,J=8.6 Hz,2H),7.14(d,J=8.6 Hz,2H),5.25(s,2H),3.49(s,3H);C9H 11 O3 [M+H] + MS(ESI) calculated for 167.1, found 167.0.

[0139] Example 2: Preparation of (trans)-5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-methoxychroman-4-one-methanol (102) [ka] Prepared as in Example 1 from B-1 (Example 2a), (345 mg, 743 μmol), MeOH (50 mL) and HCl (12N, 15 mL) to give the desired compound 102 (222 mg, 90% yield) as a white solid. 1H NMR(500 MHz,MeOD)δ 6.98-6.96(m,1H),6.96-6.85(m,2H),5.91(d,J=2.1 Hz,1H),5.88(d,J=2.2 Hz,1H),5.08(d,J=10.1 Hz,1H),4.22(d,J=10.2 Hz,1H),3.88(s,3H),3.35(s,3H);C 17 H 17 O7[M+H] + MS(ESI) calculated for 333.1, found 333.0.

[0140] Example 2a: Preparation of (trans)-3-methoxy-2-(3-methoxy-4-(methoxymethoxy)phenyl)-5,7-bis(methoxymethoxy)chroman-4-one (B-1) [ka] Prepared as in Example 1a from B-2 (Example 2b), (480 mg, 1.1 mmol), AgO (1.0 g, 4.4 mmol), and MeI (12 mL) to give B-1 (345 mg, 70% yield) as a clear oil. 1 H NMR(400 MHz,CDCl3)δ 7.28(d,J=2.1 Hz,1H),7.08(dd,J=8.3,2.1 Hz,1H),6.91(d,J=8.4 Hz,1H),6.43(d,J=2.2 Hz,1H),6.35(d,J=2.2 Hz,1H),5.32-5.24(m,3H),5.24-5.17(m,2H),5.17-5.15(m,2H),4.00(d,J=10.1 Hz,1H),3.90(s,3H),3.53(s,3H),3.53(s,3H),3.47(s,3H),3.45(s,3H);C 23 H 29 O 10 [M+H] + MS(ESI) calculated for 465.2, found 465.0.

[0141] Example 2b. Preparation of (trans)-3-hydroxy-2-(4-methoxy-3-(methoxymethoxy)phenyl)-5,7-bis(methoxymethoxy)chroman-4-one (B-2) [ka] B-3 (Example 2c) was prepared as in Example 1b from (3.77 g, 8.68 mmol), dioxane (100 mL), EtNH (4.5 mL, 43 mmol) and HO (30% wt, 107 mL, 868 mmol). Addition of approximately 85 mL of HO solution caused precipitation to give B-2 (557 mg, 14% yield) as a white solid. 1 H NMR(400 MHz,CDCl3)δ 7.36(d,J=2.1 Hz,1H),7.17(dd,J=8.3,2.1 Hz,1H),6.96(d,J=8.4 Hz,1H),6.46(d,J=2.2 Hz,1H),6.37(d,J=2.2 Hz,1H),5.42-5.22(m,4H),5.19-5.16(m,2H),4.97(d,J=12.2 Hz,1H),4.46(d,J=12.2 Hz,1H),4.01(s,1H),3.91(s,3H),3.54(s,3H),3.53(s,3H),3.47(s,3H);C 22 H 27 O 10 [M+H] + MS(ESI) calculated for 421.2, found 451.2.

[0142] Example 2c: Preparation of (E)-1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)prop-2-en-1-one (B-3) [ka] Prepared as in Example 1c from A-4 (Example 1d) (3.32 g, 13.0 mmol) and B-4 (Example 2d) (2.67 g, 13.6 mmol) in ethanol (60 mL), KOH (50% wt, 20 mL, 180 mmol) to give B-3 (5.5 g, 97% yield) as a yellow oil. 22 H 27 O9[M+H] + MS(ESI) calculated for 435.2, found 435.2.

[0143] Example 2d: Preparation of 4-methoxy-3-(methoxymethoxy)benzaldehyde (B-4) [ka] Prepared as in example 1e from isovanillin B-5 (10 g, 66 mmol), DCM (400 mL), DIPEA (16 mL, 92 mmol) and MOMCl (6 mL, 80 mmol) to give B-4 (12.7 g, 98% yield) as a white solid. 1 H NMR(400 MHz,CDCl3)δ 9.86(s,1H),7.67(d,J=2.0 Hz,1H),7.55(dd,J=8.3,1.9 Hz,1H),7.02(d,J=8.3 Hz,1H),5.29(s,2H),3.97(s,3H),3.53(s,3H);C 10 H 13 O4[M+H] + MS(ESI) calculated for 197.1, found 197.0.

[0144] Example 3: Preparation of (trans)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-methoxychroman-4-one (105) [ka] Prepared according to the procedure described in Example 1 from C-1 (Example 3a), 135 mg, 334 μmol), MeOH (100 mL) and HCl (12N, 7 mL) to give 3-O-Me-flavanonol 105 (88 mg, 83% yield) as a white solid. 1 H NMR(400 MHz,MeOD)δ 7.42(t,J=8.3 Hz,1H),6.99(d,J=1.4 Hz,1H),6.95(d,J=1.2 Hz,2H),6.50(dd,J=8.3,0.9 Hz,1H),6.47(dd,J=8.3,0.9 C17 H 17 O6 [M+H] + MS(ESI) calculated for 317.1, found 317.0.

[0145] Example 3a: Preparation of (trans)-3-methoxy-2-(4-methoxy-3-(methoxymethoxy)phenyl)-5-(methoxymethoxy)chroman-4-one (C-1) [ka] C-2 (Example-3b) was prepared from (149 mg, 414 μmol), AgO (380 mg, 1.7 mmol) and MeI (1 mL) according to the procedure described in Example 1a to give C-1 (135 mg, 88% yield) as a white solid. 1 H NMR(400 MHz,CDCl3)δ 7.38(t,J=8.3 Hz,1H),7.30(d,J=2.1 Hz,1H),7.10(ddd,J=8.3,2.1,0.6 Hz,1H),6.92(d,J=8.4 Hz,1H),6.77(dd,J=8.4,1.0 Hz,1H),6.67(dd,J=8.4,1.0 Hz,1H),5.34-5.26(m,3H),5.26-5.11(m,2H),4.07(d,J=10.3 Hz,1H),3.90(s,3H),3.54(s,3H),3.53-3.48(m,4H),3.45(d,J=0.8 Hz,3H);C 20 H 21 O7[M- - OMe] + MS(ESI) calculated for 373.1, found 373.0.

[0146] Example 3b. Preparation of (trans)-3-hydroxy-2-(4-methoxy-3-(methoxymethoxy)phenyl)-5-(methoxymethoxy)chroman-4-one (C-2) [ka] To an ice-cold (ice bath) solution of C-3 (Example-3c), (1.4 g, 3.7 mmol) in dioxane (50 mL) was added Et2NH (1.9 mL, 19 mmol) under N2, followed by slow addition of H2O2 (30% wt, 12 mL, 112 mmol) over 15 min. The reaction mixture was left stirring vigorously for 22 h (the ice bath was allowed to melt), after which LCMS analysis indicated consumption of starting material. The solution was cooled to 0 °C on an ice bath and excess hydrogen peroxide was quenched by slow addition of a solution of Na2S2O3·5H2O (250 g, 1.4 mol) in H2O (ca. 350 mL) over 30 min (CAUTION! Exothermic!) followed by extraction with EtOAc (3 x 150 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (15->50% EtOAc / Hexanes). The fractions corresponding to the product were further purified by recrystallization from EtOH (~5 mL) to give 150 mg (10% yield) of flavanonol C-2 as a white solid. 1 H NMR(400 MHz,CDCl3)δ 7.42(td,J=8.4,1.0 Hz,1H),7.38(d,J=2.1 Hz,1H),7.19(dd,J=8.4,2.1 Hz,1H),6.97(d,J=8.3 Hz,1H),6.80(dd,J=8.4,1.0 Hz,1H),6.68(dd,J=8.4,1.0 Hz,1H),5.38-5.33(m,1H),5.33-5.30(m,1H),5.30(d,J=5.1 Hz,1H),5.28-5.22(m,1H),5.01(d,J=12.3 Hz,1H),4.54(dd,J=12.4,0.9 Hz,1H),3.91(d,J=1.0 Hz,3H),3.55(d,J=1.0 Hz,3H),3.53(d,J=1.0 Hz,3H);C 19 H 19 O7[M- - OMe] + MS(ESI) calculated for 359.1, found 359.0.

[0147] Example 3c: Preparation of (E)-1-(2-hydroxy-6-(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)prop-2-en-1-one (C-3) [ka] Prepared according to the procedure described in Example 1c from C-4 (Example 3d) (1.8 g, 9.2 mmol) in ethanol (50 mL), KOH (50% wt, 20 mL, 180 mmol) and B-4 (1.9 g, 9.6 mmol) to give 2.9 g of C-3 (85% yield) as a yellow oil. 1 H NMR(400 MHz,CDCl3)δ 13.03(s,1H),7.81(d,J=4.0 Hz,2H),7.53(d,J=2.1 Hz,1H),7.33(t,J=8.3 Hz,1H),7.24(d,J=2.1 Hz,1H),6.92(d,J=8.4 C 20 H 23 O7[M+H] + MS(ESI) calculated for 375.1, found 375.0.

[0148] Example 3d: Preparation of 1-(2-hydroxy-6-(methoxymethoxy)phenyl)ethan-1-one (C-4) [ka] Example 4: Preparation of (trans)-7-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-methoxychroman-4-one (107) [ka] Prepared according to the procedure described in Example 1 from D-1 (Example 4a), (166 mg, 410 μmol), MeOH (10 mL) and HCl (12N, 7 mL) to give the desired compound 107 (58 mg, 45% yield) as a white solid.1 H NMR(400 MHz,MeOD)δ 7.70(d,J=8.7 Hz,1H),6.98(s,1H),6.94(s,2H),6.52(dd,J=8.7,2.3 Hz,1H),6.33(d,J=2.3 Hz,1H),5.11(d,J=10.3 Hz,1H),4.18(d,J=10.4 Hz,1H),3.87(s,3H),3-OMe peak overlaps with CD2HOD solvent peak at 3.32-3.28 ppm;C 17 H 17 O6 [M+H] + MS(ESI) calculated for 317.1, found 317.0.

[0149] Example 4a: Preparation of (trans)-3-methoxy-2-(4-methoxy-3-(methoxymethoxy)phenyl)-7-(methoxymethoxy)chroman-4-one (D-1) [ka] An oven-dried 40 mL vial equipped with a stir bar and Teflon cap was charged with D-2 (Example 4b), (153 mg, 392 μmol) and Ag2O (363 mg, 1.57 mmol) followed by MeI (3 mL) under N2. After heating the suspension to 45 °C with vigorous stirring for 1 day, LCMS analysis showed about 95% conversion. (The reaction rate depends on the quality of Ag2O. Freshly prepared Ag2O reacts much faster and can catalyze the C-ring opening alkylation of the subsequent flavanonol O-1. Reaction monitoring is recommended). The suspension was loaded onto a silica column and purified by silica gel chromatography (0 → 40% EtOAc / Hexane). 129 mg (81% yield) of MOM-protected 3-O-Me-flavanonol D-1 was obtained as a white solid. 1H NMR(400 MHz,CDCl3)δ 7.85(dd,J=8.8,0.7 Hz,1H),7.32(d,J=2.1 Hz,1H),7.11(ddd,J=8.3,2.1,0.6 Hz,1H),6.93(d,J=8.4 Hz,1H),6.72(ddd,J=8.8,2.3,0.7 Hz,1H),6.65(d,J=2.3 Hz,1H),5.33-5.25(m,1H),5.25-5.20(m,2H),5.19(s,2H),4.10(dd,J=10.5,0.7 Hz,1H),3.91(s,3H),3.52(d,J=0.7 Hz,3H),3.47(d,J=0.7 Hz,3H),3.41(d,J=0.7 Hz,3H);C 21 H 25 O8[M+H] + MS(ESI) calculated for 405.1, found 405.0.

[0150] Example 4b. Preparation of (trans)-3-hydroxy-2-(4-methoxy-3-(methoxymethoxy)phenyl)-7-(methoxymethoxy)chroman-4-one (D-2) [ka] To a solution of D-3 (Example 4c), (800 mg, 2 mmol) in dioxane (25 mL) was added Et2NH (1.1 mL, 11 mmol) under N2, followed by slow addition of H2O2 (30% wt, 6.6 mL, 64 mmol) over 15 min. The reaction mixture was left stirring vigorously for 18 h, after which LCMS analysis indicated consumption of starting material. The solution was cooled to 0 °C on an ice bath and excess hydrogen peroxide was quenched by slow addition of a solution of Na2S2O3·5H2O (50 g, 0.28 mol) in H2O (ca. 150 mL) over 30 min (CAUTION! Exothermic!) followed by extraction with EtOAc (3 x 100 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (25→40% EtOAc / hexanes) to afford 513 mg (62% yield) of trans-flavanonol D-2 as a white solid. 1H NMR(400 MHz,CDCl3)δ 7.86(d,J=8.8 Hz,1H),7.39(d,J=2.1 Hz,1H),7.19(dd,J=8.4,2.1 Hz,1H),6.97(d,J=8.4 Hz,1H),6.76(dd,J=8.8,2.3 Hz,1H),6.68(d,J=2.3 Hz,1H),5.37-5.24(m,2H),5.21(d,J=1.0 Hz,2H),5.04(d,J=12.3 Hz,1H),4.58(d,J=12.3 Hz,1H),3.92(s,3H),3.68(d,J=1.7 Hz,1H),3.53(s,3H),3.48(s,3H);C 20 H 23 O8[M+H] + MS(ESI) calculated for 391.1, found 391.1.

[0151] Example 4c: Preparation of (E)-1-(2-hydroxy-4-(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)prop-2-en-1-one (D-3) [ka] Prepared according to the procedure described in Example 1c from D-4 (Example 4d), (0.74 g, 3.8 mmol) in ethanol (20 mL), KOH (50% wt, 5.4 mL, 75 mmol) and B-4 (0.78 g, 4.0 mmol) to give 0.8 g of D-3 (57% yield) as a yellow solid. 1 H NMR(400 MHz,CDCl3)δ 8.10(d,J=9.0 Hz,1H),7.82(d,J=15.3 Hz,1H),7.69(d,J=15.3 Hz,1H),7.54(d,J=2.1 Hz,1H),7.42(dd,J=8.5,2.2 Hz,1H),7.07(d,J=8.5 Hz,1H),6.64(dd,J=8.9,2.5 Hz,1H),6.57(d,J=2.5 Hz,1H),5.26(d,J=2.1 Hz,4H),3.90(s,3H),3.53(s,3H),3.47(s,4H);C 20 H 23 O7[M+H] +MS(ESI) calculated for 375.1, found 375.0.

[0152] Example 4d: Preparation of 1-(2-hydroxy-4-(methoxymethoxy)phenyl)ethan-1-one (D-4) [ka] A 500 mL oven-dried round-bottom flask equipped with a stir bar and rubber septum was charged with 2',4'-dihydroxyacetophenone D-5 (6.8 g, 45 mmol) followed by dry DCM (150 mL) under N2. To the stirred suspension, DIPEA (14 mL, 80 mmol) was added slowly to give a clear solution. To the stirred clear solution, MOMCl (4.1 mL, 54 mmol) was added dropwise over 15 min. The reaction was left stirring for 18 h, after which LCMS analysis indicated consumption of starting material. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography (0→40% EtOAc / Hexanes) to give 8.5 g (97% yield) of acetophenone D-4 as a yellow oil. 1 H NMR(400 MHz,CDCl3)δ 12.61(s,1H),7.65(d,J=8.8 Hz,1H),6.60(d,J=2.4 Hz,1H),6.55(dd,J=8.9,2.5 Hz,1H),5.21(s,2H),3.48(s,3H),2.57(s,3H);C 10 H 13 O4[M+H] + MS(ESI) calculated for 197.1, found 197.2.

[0153] Example 5: Preparation of (trans)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-3,7-dimethoxychroman-4-one (113) [ka] An oven-dried 1-dram vial equipped with a stir bar and Teflon cap was charged with 102 (Example 2), (5.0 mg, 15 μmol) and K2CO3 (2.5 mg, 18 μmol) followed by a solution of MeI (2.4 mg, 17 μmol) in acetone (1 mL) under N2. After the suspension was left at 22 °C for 18 h with vigorous stirring, LCMS analysis showed approximately 50% conversion and formation of product with a small amount of by-product. The reaction mixture was filtered through a syringe filter and the solvent was removed under reduced pressure. The crude mixture was purified by preparative RP HPLC (50→54% MeCN / H2O) to give 0.9 mg (17% yield) of 113 as a white solid. 1 H NMR(500 MHz,MeOD)δ 7.00(d,J=1.8 Hz,1H),6.98-6.88(m,2H),6.10(d,J=2.3 Hz,1H),6.08(d,J=2.3 Hz,1H),5.14(d,J=10.2 Hz,1H),4.28(d,J=10.2 Hz,1H),3.90(s,3H),3.84(s,3H),3.39(s,3H);C 18 H 19 O7[M+H] + MS(ESI) calculated for 347.1, found 347.0. (Methylation at O-7 of the flavanonol core is confirmed by NOESY experiments: strong NOE signals between the methyl group and both H-6 and H-8 of the molecule.)

[0154] Example 6: Preparation of (trans)-3-ethoxy-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one (117) [ka] Prepared according to the procedure described in Example 1 from E-1 (Example 6a), (8 mg, 16 μmol), MeOH (2 mL) and HCl (12N, 1 mL) to give flavanonol 117 (6.6 mg, 99% yield) as a yellow oil. 1H NMR(500 MHz,MeOD)δ 6.87(d,J=1.6 Hz,1H),6.84(d,J=1.8 Hz,2H),5.81(d,J=2.1 Hz,1H),5.80(d,J=2.2 Hz,1H),4.96(d,J=10.3 C 18 H 19 MS(ESI) calculated for O7[M+H]+ 347.1, found 347.2.

[0155] Example 6a: Preparation of (trans)-3-ethoxy-2-(3-methoxy-4-(methoxymethoxy)phenyl)-5,7-bis(methoxymethoxy)chroman-4-one (E-1) [ka] Prepared according to the procedure described in Example 1a from B-2 (Example 2b), (9 mg, 20 μmol), AgO (20 mg, 80 μmol), and EtI (1 mL) to give E-1 (8 mg, 83% yield) as a clear oil. 1 H NMR(500 MHz,CDCl3)δ 7.26-7.20(m,1H),7.03(dd,J=8.4,2.1 Hz,1H),6.91-6.72(m,1H),6.37(d,J=2.2 Hz,1H),6.29(d,J=2.2 Hz,1H),5.26-5.18(m,3H),5.17-5.13(m,1H),5.12-5.04(m,3H),3.99(d,J=10.4 Hz,1H),3.83(s,3H),3.77(dt,J=9.2,7.1 Hz,1H),3.46(d,J=2.8 Hz,3H),3.44(s,3H),3.40(s,2H),3.28(dq,J=9.0,6.9Hz,1H),0.98(t,J=7.0 Hz,3H);C 24 H 31 O 10 MS(ESI) calculated for [M+H]+ 479.2, found 479.2.

[0156] Example 7: Preparation of (trans)-5,7-dihydroxy-3-methoxy-2-(3,4,5-trihydroxyphenyl)chroman-4-one (G-1) [ka] Prepared according to the procedure described in Example-1 from G-1 (Example 7a), (6 mg, 11 μmol), MeOH (3 mL) and HCl (12N, 1.5 mL) to give flavanonol 121 (3.1 mg, 86% yield) as a yellow oil. 1 C 16 H 15 O8[M+H] + MS(ESI) calculated for 335.1, found 335.0.

[0157] Example 7a: Preparation of (trans)-3-methoxy-5,7-bis(methoxymethoxy)-2-(3,4,5-tris(methoxymethoxy)phenyl)chroman-4-one (G-1) [ka] An oven-dried 4 mL vial equipped with a stir bar and Teflon cap was charged with G-2 (Example 7b), (14 mg, 26 μmol) and Ag2O (24 mg, 104 μmol) followed by MeI (0.5 mL) under N2. After heating the suspension to 40 °C for 24 h with vigorous stirring, LCMS analysis showed approximately 50% conversion of starting material (reaction rate depends on Ag2O quality. Freshly prepared Ag2O reacts much faster and can catalyze the C-ring opening subsequent alkylation of flavanonol O-1. Reaction monitoring is recommended.) The suspension was loaded onto a silica column and purified by silica gel chromatography (0→75% EtOAc / hexanes) to give 6 mg (42% yield) of MOM-protected 3-OMe-flavanonol G-1 as a white solid.1 H NMR(500 MHz,MeOD)δ 7.00(s,2H),6.48(d,J=2.2 Hz,1H),6.36(d,J=2.2 Hz,1H),5.25(s,2H),5.24-5.16(m,7H),5.12(s,2H),4.13(d,J=9.6 Hz,1H),3.60(s,3H),3.49(s,3H),3.48(s,6H),3.46(s,3H),3.39(s,3H);C 26 H 35 O 13 [M+H] + MS(ESI) calculated for 555.2, found 555.2.

[0158] Example 7b: Preparation of (trans)-3-hydroxy-5,7-bis(methoxymethoxy)-2-(3,4,5-tris(methoxymethoxy)phenyl)chroman-4-one (G-2) [ka] A 100 mL round bottom flask equipped with a stir bar and rubber septum was charged with G-3 (Example 7c) (210 mg, 360 μmol) followed by THF (15 mL) and a solution of Na2CO3 (77 mg, 720 μmol) in H2O (4 mL) under N2. The resulting suspension was stirred at 22° C. for 3 h, at which point the reaction mixture was heated to 50° C. and water was added until the cloudy solution became clear (approximately 2 mL). Once a clear solution was formed, the heat was removed and the reaction mixture was left stirring at 22° C. under N2 for 12 h, after which EtOAc (40 mL) was added followed by saturated aqueous NH4Cl. The layers were separated and the aqueous layer was further extracted with EtOAc (3×50 mL). The organics were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by preparative RP HPLC (10→90% MeCN / H2O) to afford 91 mg (47% yield) of flavanonol G-2 as a white solid. 1H NMR(500 MHz,DMSO-d6)δ δ 6.99(s,2H),6.40(d,J=2.3 Hz,1H),6.32(d,J=2.2 Hz,1H),5.44(d,J=2.5 Hz,1H),5.28-5.23(m,4H),5.23-5.16(m,4H),5.08(s,2H),5.07(d,J=11.5 Hz,1H),4.46(dd,J=11.2,2.5 Hz,1H),3.53(s,3H),3.43(s,3H),3.42(s,6H),3.38(s,3H);C 25 H 33 O 13 [M+H] + MS(ESI) calculated for 541.2, found 541.2.

[0159] Example 7c: Preparation of (trans)-3-acetoxy-5,7-bis(methoxymethoxy)-2-(3,4,5-tris(methoxymethoxy)phenyl)chroman-4-one (G-3) [ka] A 100 mL round-bottomed vial equipped with a stir bar and rubber septum was charged with G-4 (Example 7d) (259 mg, 715 μmol) and dry DCM (20 mL) under N2. The resulting solution was cooled to 0° C. on an ice bath, followed by the addition of a solution of DIPEA (1.9 mL, 11 mmol) and DMAP (175 mg, 1.43 mmol) in DCM (1 mL). To the stirred mixture was added MOMCl (543 μL, 7.15 mmol) dropwise. The reaction mixture was left stirring and the ice bath was allowed to melt. After 21 h, additional MOMCl (100 μL, 1.32 mmol) was added at 22° C. After all was stirred at 22° C. for 8 h, the reaction was quenched with saturated aqueous NH4Cl (25 mL) followed by extraction with DCM (3×20 mL). The organic layers were combined, dried over MgSO, filtered, and concentrated under reduced pressure. The crude residue was purified by preparative RP HPLC (10→90% MeCN / H2O) to give 170 mg (41% yield) of G-3 as a white oily solid. 1H NMR(500 MHz,DMSO-d6)δ 7.00(s,2H),6.42(d,J=2.2 Hz,1H),6.36(d,J=2.2 Hz,1H),5.66(d,J=12.0 Hz,1H),5.52(d,J=12.0 Hz,1H),5.26(s,2H),5.24(s,2H),5.22(d,J=6.7 Hz,2H),5.18(d,J=6.7 C 27 H 35 O 14 [M+H] + MS(ESI) calculated for 583.2, found 583.2.

[0160] Example 7d: Preparation of (trans)-3-acetoxy-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)chroman-4-one (G-3) [ka] A 20 mL microwave vial equipped with a stir bar was charged with (+)-ampelopsin (G-5), (550 mg, 1.72 mmol) and AcOH (10 mL). The vial was sealed and the solution was degassed by vigorously bubbling N2 through it for 15 min. The sealed solution was heated at 120 °C for 23 h. The solvent was removed under reduced pressure and the crude residue was purified by preparative RP HPLC (10 -> 90% MeCN / H2O) to give 259 mg (49% yield) of racemic G-4 as a yellow oil. 1 C 17 H 15 O9[M+H] + MS(ESI) calculated for 363.1, found 363.0.

[0161] Example 8: Preparation of (+)-(trans)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-methoxychroman-4-one (122) and (-)-(trans)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-methoxychroman-4-one (123) [ka] The synthetic racemic 102 (110 mg, 39 μM) was separated by semi-preparative chiral RP HPLC (35% MeCN / HO / 0.1% formic acid, isocratic, 15 min at 20 mL / min, multiple injections). Fractions corresponding to the first peak were combined and concentrated under vacuum to give 52 mg (95% yield) of 122 as a white solid, [α] D 20 +88.3° (c 0.08, EtOH), which was determined to be >99% ee by chiral HPLC analysis. Fractions corresponding to the second peak were combined and repurified to give 34 mg (62% yield) of 123 as a white solid, [α] D 20 At -71.9° (c 0.16, EtOH), this material was determined to be 99% ee by chiral HPLC analysis. The remaining material remained in the mixed fraction. 1 1 H NMR and MS data were identical to that of racemic 102.

[0162] Example 9 - Compounds 103, 104, 106, 108-112 and 114-116 Compounds 103, 104, and 106 were synthesized in a similar manner to the protocols described for compounds 101 and 102 (Examples 1 and 2). Compounds 118-120 were prepared in a similar manner to the protocols described for compound 117 (Example 6). Compounds 108-116 can be synthesized in a similar manner. Table 2 shows the analytical data (MS(m / z[M+H] + ) and 1H NMR spectral data are provided. The MS and NMR data for enantiopure compounds 122–129 are identical to those for their corresponding racemates 101, 102, 105, and 107.

[0163] [Table 2-1] [Table 2-2]

[0164] Example 10 Compounds 124-129 were prepared by chiral separation of their corresponding racemates (compounds 101, 105 and 107) using a procedure similar to that described in Example 8. Table 3 summarizes the optical data and enantiomeric excess of enantiomers 124-129.

[0165] [Table 3]

[0166] Example 11 - Compound Testing Each of compounds 101-107, 113 and 117-129 was synthesized or isolated from the corresponding synthetic racemate. The compounds were then tested in an in vitro cell-based assay with cells overexpressing the T1R sweet taste receptor. Sweet dose-response curves were recorded and EC50s were calculated. Table 4 shows the calculated EC50 values ​​of the tested compounds.

[0167] [Table 4]

[0168] Example 12 - Sensory evaluation of compounds using human panelists Test samples containing selected experimental compounds were sensorily evaluated for sweetness intensity relative to a 1.5% sucrose solution by a trained sensory panel of at least eight panelists. The highest concentration of a compound at which the panelists judged it to be less sweet than a 1.5% sucrose solution was taken as its threshold concentration (TC). The sweetness of 6% sucrose solutions containing each compound at its threshold concentration (TC) was then evaluated in comparison to pure sucrose solutions of various concentrations. The results are reported in Table 5. Table 5 summarizes the sensory evaluation data for compounds 101, 102, 105, 107 and 122-125, 127, and 128.

[0169] [Table 5]

Claims

1. A taste-modifying compound which is a compound of formula (I) or a salt thereof: 【Chemistry 1】 [In the formula, R １ , R ２ , R ３ and R ４ are each independently a hydrogen atom, C １－６ Alkyl, —OH or —O—(C １－６ alkyl), R ５ , R ６ , R ７ , R ８ and R ９ are each independently a hydrogen atom, C １－６ alkyl, —OH, or —O—(C １－６ alkyl), R Ｘ is C １－６ is alkyl.

2. R １ , R ２ , R ３ , and R ４ are, independently of one another, a hydrogen atom, methyl, hydroxy or methoxy, R ５ , R ６ , R ７ , R ８ , and R ９ are, independently of one another, a hydrogen atom, methyl, hydroxy or methoxy, R Ｘ is methyl or ethyl; The flavor-modifying compound of claim 1 .

3. R ２ and R ４ The taste-modifying compound of claim 1 , wherein both are hydrogen atoms.

4. R ５ , R ６ , and R ９ 10. The flavor-modifying compound of claim 1, wherein each is a hydrogen atom.

5. 10. The flavor-modifying compound of claim 1, which is Compound 101, Compound 102, Compound 103, Compound 104, Compound 105, Compound 106, Compound 107, Compound 108, Compound 109, Compound 110, Compound 111, Compound 112, Compound 113, Compound 114, Compound 115, Compound 116, or a edible acceptable salt of any of the foregoing.

6. Use of a taste-modifying compound according to any one of claims 1 to 5 to reduce the bitter taste of an ingestible composition.

7. 7. The use of claim 6, wherein the concentration of the taste-modifying compound used in the ingestible composition ranges from 0.1 ppm to 1000 ppm.

8. The use of claim 6 , wherein the ingestible composition comprises one or more bitter tastants.

9. The bitter substance may be a high-intensity sweetener, such as acesulfame potassium, aspartame, neotame, cyclamate, saccharin, sucralose, steviol glycosides (e.g., rebaudioside A, rebaudioside B, rebaudioside M, rebaudioside D, or rebaudioside E), and mogrosides (e.g., mogroside III, mogroside IV, mogroside V, siamenoside I, isomogroside V, mogroside IV, Ｅ , Isomogroside IV, Mogroside III Ｅ 11-oxomogroside V, or siamenoside I), or any combination thereof.

10. 9. The use according to claim 8, wherein the bitter substance is a potassium salt, such as potassium chloride.

11. 9. The use according to claim 8, wherein the bitter tastant is a vegetable protein, such as pea protein, soy protein, almond protein, cashew protein, canola (rapeseed) protein, chickpea protein, broad bean protein, sunflower protein, wheat protein, oat protein, barley protein, potato protein, or any combination thereof.

12. 9. The use of claim 8, wherein the bitter tastant is a pharmaceutical compound such as atropine, brinzolamide, chloramphenicol, chloroquine, clindamycin, dexamethasone, digoxin, diltiazem, diphenhydramine, docusate, dorzolamide, doxepin, doxylamine, enalapril, erythromycin, esomeprazole, famotidine, gabapentin, ginkgolide A, guaifenesin, L-histidine, lomefloxacin, methylprednisolone, ofloxacin, oleuropein, oxyphenonium, pirenzepine, prednisone, ranitidine, trapidil, trimethoprim, cetirizine, or any combination thereof.

13. Use of a taste-modifying compound according to any one of claims 1 to 5 to enhance the sweetness of an ingestible composition.

14. 14. The use of claim 13, wherein the concentration of the taste-modifying compound used in the ingestible composition ranges from 0.1 ppm to 1000 ppm.

15. 14. The use of claim 13, wherein the ingestible composition comprises one or more bitter tastants.

16. An ingestible composition comprising a taste-modifying compound according to any one of claims 1 to 5 and a bulking agent.

17. 17. The ingestible composition of claim 16, wherein the ingestible composition comprises a sweetener.

18. 17. The ingestible composition of claim 16, wherein the taste-modifying compound is present in the ingestible composition at a concentration ranging from 0.1 ppm to 1000 ppm.

19. 17. A flavored product comprising the ingestible composition of claim 16.

20. 20. The flavored product of claim 19, which is a beverage product, a food product, an oral care product, or a pharmaceutical product.

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