Use of flavanone compounds and flavor modifiers

Abstract

This disclosure relates, in general, to 3-acyloxyflavanone compounds and the use of such compounds to impart and / or enhance sweetness, mask bitterness, enhance mouthfeel, or mask astringency. In certain embodiments, such compounds are used in combination with other flavonoids or dihydrochalcones. In certain embodiments, this disclosure provides edible compositions comprising such flavanone compounds. In some related embodiments, the edible compositions are or are included in various flavored products, such as food, beverage products, pharmaceutical products, or oral care products.

Description

[Technical Field]

[0001] This disclosure relates, in general, to 3-acyloxyflavanone compounds and the use of such compounds to impart and / or enhance sweetness, mask bitterness, enhance mouthfeel, or mask astringency. In certain embodiments, such compounds are used in combination with other flavonoids or dihydrochalcones. In certain embodiments, this disclosure provides edible compositions comprising such flavanone compounds. In some related embodiments, the edible compositions are or are included in various flavored products, such as food, beverage products, pharmaceutical products, or oral care products.

[0002] Explanation of related technologies The taste system provides sensory information about the chemical composition of the external environment. Taste transmission is one of the more sophisticated forms of chemically evoked sensation in animals. Taste signaling is found throughout the animal kingdom, from simple metazoans to the most complex vertebrates. Mammals are thought to have five basic taste modes: sweet, bitter, sour, salty, and umami.

[0003] Sweetness is the most commonly perceived taste when consuming sugary foods. Mammals generally perceive sweetness as pleasurable, except in excessive amounts. Caloric sweeteners such as sucrose and fructose are archetypal examples of sweetening substances. While various zero-calorie and low-calorie alternatives exist, these caloric sweeteners remain the primary means by which ingestible products induce the perception of sweetness upon consumption.

[0004] Metabolic disorders and related conditions, such as obesity, diabetes, and cardiovascular disease, are major public health concerns worldwide. Their prevalence is increasing at an alarming rate in almost all developed countries. Calorie-rich sweeteners contribute significantly to this trend, as they are included in a variety of packaged food and beverage products to enhance consumer palatability. Often, zero-calorie or low-calorie substitutes can be used in place of sucrose or fructose in foods and beverages. However, these compounds impart a different sweetness than calorie-rich sweeteners, and many consumers do not consider them suitable substitutes. Furthermore, such compounds can be difficult to incorporate into certain products. While they may sometimes be used as partial substitutes for calorie-rich sweeteners, their mere presence can cause many consumers to perceive unpleasant tastes, including astringency, bitterness, and metallic and licorice flavors. Therefore, the adoption of low-calorie sweeteners faces certain challenges.

[0005] Sweetness enhancement offers 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 their sweetness, thereby reducing the amount of such calorie sweeteners used in various food or beverage products. However, in addition to enhancing the perceived sweetness of the primary sweetener, such compounds also alter the perceived taste of the sweetener. Consequently, many consumers find consuming such sweetness-enhanced products less pleasant compared to unenhanced alternatives with higher calories. Therefore, there remains a need to discover compounds that enhance the sweetness of calorie sweeteners without altering their perceived taste, thus avoiding the pleasure consumers experience when consuming products containing such sweeteners.

[0006] overview This disclosure relates to the finding that certain flavanones and related compounds can be used to impart and / or enhance sweetness with a more natural taste, and, if applicable, to mask bitterness, enhance mouthfeel, or mask astringency.

[0007] In a first aspect, the present disclosure provides a flavoring compound which is a compound of formula (I) or a salt thereof: [ka] [In the formula, R 1 and R 2 These are, independently of each other, a hydrogen atom, -OH, or -OCH3, R 3 , R 4 , and R 5 These are, independently of each other, a hydrogen atom, -OH, or -OCH3, R is methyl, ethyl, isopropyl, or benzyl.

[0008] In a second embodiment, the Disclosure provides the use of flavor-modifying compounds of the first embodiment for enhancing the sweetness of an edible composition. In certain relevant embodiments, the Disclosure provides a method for enhancing the sweetness of an edible composition, comprising introducing a flavor-modifying compound of the first embodiment into the edible composition. In some embodiments, the edible composition comprises one or more sweeteners, such as caloric or non-caloric sweeteners. In some embodiments, the edible composition comprises one or more flavonoids or dihydrochalcones.

[0009] In a third aspect, the present disclosure provides the use of a flavor modulating compound of the first aspect for reducing the bitterness of an ingestible composition. In certain related aspects, the present disclosure provides a method for reducing the bitterness of an ingestible composition, the method comprising introducing a flavor modulating compound of the first aspect into an ingestible composition. In some embodiments, the ingestible composition comprises one or more bitter substances, 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 the use of a flavor modulating compound of the first aspect for reducing 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 modulating compound of the first aspect into an 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 modulating compound of the first aspect for enhancing the mouthfeel of an ingestible composition. In certain related aspects, the present disclosure provides a method for enhancing the mouthfeel of an ingestible composition, the method comprising introducing a flavor modulating compound of the first aspect into an 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 modulating 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 substances, such as high-intensity sweeteners or certain bitter compounds.

[0013] In a seventh aspect, the present disclosure provides a flavored product comprising an 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 in the following detailed description, drawings, summary, 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 describe any preferred composition or preferred method or to limit the scope of the claimed invention.

Brief Description of the Drawings

[0016] [Figure 1] It is a diagram showing a chemical formula representing a flavor - adjusting compound disclosed herein. In the formula, R1 and R2 are, independently of each other, a hydrogen atom, -OH, or -OCH3, R3, R4, and R5 are, independently of each other, a hydrogen atom, -OH, or -OCH3, and R is methyl, ethyl, isopropyl, or benzyl.

[0017] Detailed Description The following detailed description explains various aspects and embodiments provided herein. This description is to be read from the perspective of one of ordinary skill in the relevant art. Accordingly, information well - known to such persons is not necessarily included.

[0018] Definitions The following terms and phrases have the meanings set forth below unless otherwise specified herein. This disclosure may utilize other terms and phrases not expressly defined herein. Such other terms and phrases have the meanings that a person skilled in the art would have in the context of this disclosure. Where applicable, a term or phrase may be defined in the singular or plural form. Where applicable, it is understood that any singular term may include its plural counterpart, and vice versa, unless expressly indicated otherwise.

[0019] "Sweetener" refers to a compound that produces a detectable sweetness in a subject, or its ingestible salt, such as a compound that activates T1R2 and T1R3 taste receptors in vivo or in vitro.

[0020] "Bitter substance" refers to a compound that produces a detectable bitter taste in a subject, or its ingestible salt, such as a compound that activates one or more T2R taste receptors in vivo or in vitro.

[0021] As used herein, the singular forms "a," "an," and "the" refer to multiple entities unless the context clearly indicates otherwise. For example, a reference to "substituent" includes one substituent and two or more substituents, etc.

[0022] Where used herein, “for example,” “for instance,” “such as,” or “including” means to provide examples that further clarify a more general subject. Unless otherwise noted, such examples are provided solely to aid in understanding the embodiments shown in this disclosure and are not intended to limit them in any way. Furthermore, these terms do not imply any priority of any kind over the disclosed embodiments.

[0023] As used herein, “comprise,” “comprises,” “comprising,” or “comprised of” refers to an open group, meaning that the group may include additional members in addition to those explicitly listed. For example, the phrase “includes A” means that A must exist, but other members may also exist. The terms “include,” “have,” and “composed of,” and their grammatical variations, have the same meaning. In contrast, “consist of,” “consists of,” or “consisting of” refers to a closed group. For example, the phrase “consisting of A” means that only A and A exist.

[0024] As used herein, “optional” means that the events described thereafter may or may not occur. In some embodiments, the optional events do not occur. In some other embodiments, the optional events occur one or more times.

[0025] As used herein, “or” should be given the broadest reasonable interpretation and not limited to the interpretation that it is either one or the other. Thus, the phrase “containing A or B” means that A exists and B does not exist, or B exists and A does not exist, or both A and B exist. Furthermore, for example, if A defines a class that may have multiple members, such as A1 and A2, then one or more members of the class may exist simultaneously.

[0026] Chemical structures are often represented using a "skeleton" form in which carbon atoms are not explicitly shown, and hydrogen atoms bonded to carbon atoms are completely omitted. For example, structure [ka] represents butane (i.e., n - butane). Further, an aromatic group such as benzene is represented by showing one of the contributing resonance structures. For example, the structure [Chemical formula] represents toluene.

[0027] As used herein, the term "flavor - modulating compound" refers to any compound of formula (I), or a salt thereof, and any embodiment thereof described herein.

[0028] Other terms, even if not included in this subsection, are defined elsewhere in this specification.

[0029] Flavor - modulating compound In certain embodiments, the present disclosure provides a flavor - modulating compound that is a compound of formula (I) or a salt thereof: [Chemical formula] [wherein, R 1 and R 2 are, independently of each other, a hydrogen atom, - OH, or - OCH3, R 3 , R 4 , and R 5 are, independently of each other, a hydrogen atom, - OH, or - OCH3, R is methyl, ethyl, isopropyl, or benzyl.]

[0030] The substituents R 1 and R 2 can have any suitable value within the scope of the above - defined. In some embodiments, at least one of R 1 and R 2 is not a hydrogen atom. In some embodiments, R 1 and R 2 are, independently of each other, a hydrogen atom or - OH. In some embodiments, R 1 is - OH, and R 2R is a hydrogen atom. In some embodiments, R 1 R is a hydrogen atom, 2 is -OH. In some embodiments, R 1 is -OH, and R 2 It is -OH.

[0031] Substituent R 3 , R 4 , and R 5 R can have any suitable value within the range of the above definition. In some embodiments, R 3 and R 5 One of them is a hydrogen atom. In some embodiments, R 3 and R 5 Both are hydrogen atoms. In some embodiments, R4 is -OH and R 3 and R 5 These are each hydrogen atoms. In some embodiments, R 3 is -OH, and R 4 It is -OCH3, and R 5 This is a hydrogen atom.

[0032] The substituent R may have any suitable value within the range of the above definition. In some embodiments, R is methyl or ethyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. In some embodiments, R is isopropyl. In some embodiments, R is benzyl.

[0033] Table 1 shows examples of flavor-modifying compounds of the present disclosure. In some embodiments, the flavor-modifying compound is compound 101 or an edible salt thereof. In some embodiments, the flavor-modifying compound is compound 102 or an edible salt thereof. In some embodiments, the flavor-modifying compound is compound 103 or an edible salt thereof. In some embodiments, the flavor-modifying compound is compound 104 or an edible salt thereof. In some embodiments, the flavor-modifying compound is compound 105 or an edible salt thereof. In some embodiments, the flavor-modifying compound is compound 106 or an edible salt thereof.

[0034] [Table 1-1] [Table 1-2]

[0035] If the flavor-modifying compounds disclosed herein have at least one chiral center, they may exist as individual enantiomers and diastereomers, or as mixtures of such isomers. In some embodiments relating to the second aspect, the sweetness-enhancing compounds have considerable enantiomer purity.

[0036] The separation of individual isomers or the selective synthesis of individual isomers can be achieved by applying various methods well known to those skilled in the art. Unless otherwise specifically indicated (for example, when the stereochemistry of the chiral center is explicitly indicated), all such isomers and mixtures thereof are included in the range of compounds disclosed herein. Furthermore, the compounds disclosed herein may exist in one or more crystalline or amorphous forms. Unless otherwise specifically indicated, all such forms are included in the range of compounds disclosed herein, including any polymorphic forms. In addition, some of the compounds disclosed herein may form solvates (i.e., hydrates) with water or with common organic solvents. Unless otherwise specifically indicated, such solvates are included in the range of compounds disclosed herein.

[0037] Those skilled in the art will recognize that some of the structures described herein may be resonance forms or tautomers of compounds that can be adequately represented by other chemical structures, even in the kinetic case. Those skilled in the art will also recognize that such structures may represent only a very small sample of such compounds. Such resonance forms or tautomers are not shown herein, but such compounds are considered to be within the range of structures shown.

[0038] Isotopes may be present in the compounds described. Each chemical element represented in the structure of a compound may contain any isotope of that element. For example, in the structure of a compound, the presence of a hydrogen atom in the compound may be explicitly disclosed or understood. At any position in a compound where a hydrogen atom may be present, the hydrogen atom may be any isotope of hydrogen, including but not limited to hydrogen-1 (practium) and hydrogen-2 (deuterium). Thus, references to compounds herein encompass all potential isotopic forms unless the context clearly indicates otherwise.

[0039] In some embodiments, the flavor-modifying compounds disclosed herein can form acidic and / or basic salts in the presence of phenol, amino, and / or carboxyl groups or similar groups. Ingestable acid addition salts can be formed with inorganic and organic acids. Examples of inorganic acids from which salts can be derived include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids from which salts can be derived include 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, and salicylic acid. Ingestable salts can be formed using inorganic and organic bases. Examples of inorganic bases from which salts can be derived include bases containing sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, and aluminum, 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 unstable hydrogen from the compound, and inorganic cations, such as Li + kaNa + , K + Mg 2+ and Ca 2+This provides a salt form containing the following: Examples of organic bases from which the salt may be derived include primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and specifically isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the salt is an edible salt suitable for inclusion in edible compositions such as food or beverage products. In some embodiments, the edible salt is a sodium or potassium salt.

[0040] Usage and Method In certain embodiments, the Disclosure provides the use of a first-mode flavoring compound for enhancing the sweetness of an edible composition. In certain related embodiments, the Disclosure provides a method for enhancing the sweetness of an edible composition, comprising introducing a first-mode flavoring compound into the edible composition.

[0041] In certain embodiments, the Disclosure provides the use of a first-mode flavoring compound for reducing the bitterness of an edible composition. In certain related embodiments, the Disclosure provides a method for reducing the bitterness of an edible composition, comprising introducing a first-mode flavoring compound into the edible composition.

[0042] In certain embodiments, the Disclosure provides the use of a first-mode flavor modifier compound to reduce the astringency of an edible composition (e.g., the lingering aftertaste of a high-strength sweetener or licorice aftertaste). In certain related embodiments, the Disclosure provides a method for reducing the astringency of an edible composition, which includes introducing a first-mode flavor modifier compound into the edible composition.

[0043] In certain embodiments, the Disclosure provides the use of a first-mode flavoring compound to enhance the mouthfeel of an edible composition. In certain related embodiments, the Disclosure provides a method for enhancing the mouthfeel of an edible composition, which includes introducing a first-mode flavoring compound into the edible composition.

[0044] The uses and methods described above include ingestible compositions. In addition to the characteristics of the ingestible compositions described above, the ingestible compositions may incorporate any of the characteristics or combinations of characteristics described below.

[0045] Ingestable compositional materials In certain embodiments, the Disclosure provides an edible composition comprising a flavoring compound according to the embodiments described above. When introduced or used in an edible composition, the flavoring compound is used or introduced in the edible composition at concentrations ranging from 0.01 ppm to 1000 ppm, or 0.01 ppm to 900 ppm, or 0.01 ppm to 800 ppm, or 0.01 ppm to 700 ppm, or 0.01 ppm to 600 ppm, or 0.1 ppm to 500 ppm, or 0.1 ppm to 400 ppm, or 0.1 ppm to 300 ppm, or 0.1 ppm to 200 ppm, or 1 ppm to 100 ppm, or 1 ppm to 80 ppm, or 1 ppm to 60 ppm, or 1 ppm to 50 ppm, or 1 ppm to 40 ppm.

[0046] In some embodiments, the ingestible composition contains one or more bitter substances. In some embodiments, the bitter substances are 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 These are high-strength sweeteners such as 11-oxomogloside V or the 1,6-α isomer of siamenoside I. Therefore, flavor-modifying compounds can be appropriately used in reduced-sugar or zero-sugar products to reduce the bitterness imparted by low-calorie or zero-calorie sweeteners.

[0047] In some embodiments, the bittering substance is a potassium salt, such as potassium chloride, and is often used as a partial or complete substitute for sodium chloride in certain low-sodium or zero-sodium foods. Therefore, flavor-modifying compounds can be appropriately used in such products to reduce the bitterness imparted by the potassium salt.

[0048] In some embodiments, the bitter substance is a non-animal protein such as a plant protein, algal protein, or fungal protein. In some embodiments, the ingestible composition contains a plant protein. Non-limiting examples of plant proteins 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 a partial or complete substitute for animal proteins in dairy and meat substitutes. Therefore, flavor modifiers can be appropriately used in such products to reduce the bitterness imparted by non-animal proteins. By blocking the bitterness of such proteins, flavor modifiers can reduce the perceived cereal and green notes experienced by consumers.

[0049] In some embodiments, bitter substances include caffeine, quinine, green tea, catechins, polyphenols (e.g., polyphenol antioxidants), tannins, green robusta coffee extract, green coffee extract, menthol, and the like. Such compounds are commonly found in various natural foods, such as tea and coffee, as well as in packaged foods, such as instant tea, instant coffee, and packaged beverages. When one or more such bitter substances are present, flavor-modifying compounds are appropriately used to mask the bitterness of such compounds and improve the taste of the product as perceived by the consumer.

[0050] In some embodiments, the bitter substance is a pharmaceutical compound. Non-limiting examples of bitter pharmaceutical compounds include atropine, brinzolamide, chloramphenicol, chloroquine, clindamycin, dexamethasone, digoxin, diltiazem, diphenhydramine, docusate, dorzolamide, doxepin, doxylamine, enalapril, erythromycin, esomeprazole, famotidine, gabapentin, gincolide 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 an oral pharmaceutical formulation, flavor modifiers are appropriately used to block the bitterness of such compounds and improve the taste of the pharmaceutical product as perceived by the consumer.

[0051] In some embodiments, bitter substances are oral care ingredients. Many oral care ingredients impart an unpleasant bitterness, which must be masked or blocked to improve consumer acceptance of the product. Non-limiting examples of such oral care ingredients include menthol, menthol analogues, mint extract, 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, cubebol, and any combination thereof. When one or more such oral care compounds are used in an oral care product, flavor modifiers are appropriately used to block the bitterness of such compounds and improve the taste of the oral care product as perceived by the consumer.

[0052] In some embodiments, the bitter substance is a bittering agent found in citrus fruits, such as limonin, nomelin, or naringin. Many citrus-containing preparations impart an unpleasant bitterness, which must be masked or blocked to improve consumer acceptance of the product. This unpleasant bitterness may sometimes be due to citrus greening disease, a condition in which citrus fruits turn green before they are fully ripe. When one or more such citrus bittering agents are present in the product, flavor-modifying compounds are appropriately used to block the bitterness of such compounds and improve the taste of the citrus product as perceived by consumers.

[0053] In some embodiments, the ingestible composition comprises one or more flavanones or dihydrochalcones. In certain embodiments, such flavanones act synergistically with the flavor-modifying compounds disclosed herein to reduce bitterness, enhance the perception of sweetness, or reduce sourness. In some embodiments, the flavanone is eriodictiol, hesperetin, hesperidin, homoeriodictiol, naringenin, hesperitin dihydrochalcone, phloretin, or any combination thereof. In some further embodiments, the flavanone is eriodictiol. In some other embodiments, the flavanone is homoeriodictiol. Such flavanones may be present in the ingestible composition at any appropriate concentration, for example, in the range of 0.01 ppm to 1000 ppm, or 0.01 ppm to 900 ppm, or 0.01 ppm to 800 ppm, or 0.01 ppm to 700 ppm, or 0.01 ppm to 600 ppm, or 0.1 ppm to 500 ppm, or 0.1 ppm to 400 ppm, or 0.1 ppm to 300 ppm, or 0.1 ppm to 200 ppm, or 1 ppm to 100 ppm, or 1 ppm to 80 ppm, or 1 ppm to 60 ppm, or 1 ppm to 50 ppm, or 1 ppm to 40 ppm.

[0054] In some embodiments, the ingestible composition includes a sweetener or a combination of sweeteners. In some embodiments, the sweetener is a sweetener composition containing 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-leucose. 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), hydrolyzed hydrogenated starch (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), carrelam 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 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 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.

[0055] Sweeteners may also include, for example, sweetener compositions containing 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), hydrolyzed hydrogenated starch (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 include, in some embodiments, erythritol, maltitol, mannitol, sorbitol, lactitol, xylitol, isomalt, propylene glycol, glycerol (glycerin), treitol, galactitol, palatinose, reduced isomalt-oligosaccharides, reduced xylo-oligosaccharides, reduced gentio-oligosaccharides, reduced maltose syrup, reduced glucose syrup, isomaltulose, maltodextrin, etc., and any other sugar alcohols or combinations thereof that can be reduced without adversely affecting the taste.

[0056] The sweeteners include agave inulin, agave nectar, agave syrup, amazake, blazein, brown rice syrup, coconut crystals, coconut sugar, coconut syrup, date sugar, fructan (also called inulin fiber, fructo-oligosaccharide, or oligo-fructose), green stevia powder, and stevia rebaudiana. Rebaudiana), rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside E, rebaudioside F, rebaudioside I, rebaudioside H, rebaudioside L, rebaudioside K, rebaudioside J, rebaudioside N, rebaudioside O, rebaudioside M and other sweet stevia-based 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., sugar maple (Acer saccharum), black maple (Acer nigrum), American flowering tree (Acer rubrum), silver maple (Acer (including sap extracted from Acer platanoides, Acer negundo, Acer macrophyllum, Acer grandidentatum, Acer glabrum, and Acer mono), maple syrup, maple sugar, walnut sap (e.g., sap extracted from Juglans cinerea, Juglans nigra, Juglans ailatifolia, and Juglans regia), birch sap (e.g., Betula papyrifera, Betula alleghaniensis, Betula lenta, and Betula lenta) Betula populifolia, Betula nigra)(including sap extracted from pendula), European maple sap (e.g., sap extracted from the American sycamore (Platanus occidentalis)), ironwood sap (e.g., sap extracted from the American sycamore (Ostrya)) Sap extracted from Virginiana, Muscovado, molasses (e.g., brown sugar molasses), molasses sugar, monatin, monellin, cane sugar (also called natural sugar, unrefined cane sugar, or sucrose), palm sugar, panochá, 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 flour, beet sugar, cane sugar, crystallized juice, caramel, carbitol, carob syrup, castor sugar, hydrogenated starch hydrolates, hydrolyzed cane juiceJuice), hydrolyzed starch, invert sugar, anethole, arabinogalactan, alope, syrup, P-4000, acesulfame potassium (also known as acesulfame K or ace-K), alitame (also known as acrame), advantame, aspartame, bayunoside, neotame, benzamide derivatives, bernadame, canderel, carrelam and other guanidine-based sweeteners, dietary fiber, corn sugar, coupling sugar, curculin, cyclamate, cyclocarioside Demerara, Dextran, Dextrin, Saccharified Malt, Dulcin, Sucrose, Vulgin, Dulcoside A, Dulcoside B, Emulin, Enoxolone, Maltodextrin, Saccharin, Estragol, Ethyl Maltol, Glycine, Gluconic Acid, Gluconolactone, Glucosamine, Glucuronic Acid, Glycerol, Glycine, Glyciphyllin, Glycyrrhizin, Glycyrrhetinic Acid Monoglucuronide, Golden Sugar, Yellow Sugar, Goldden Syrup, Granulated Sugar, Gynostemma pentaphyllum, Hernandulcin, Isomerized Liquid sugar, jalab, chicory root dietary fiber, kynurenine derivatives (including N'-formyl-kynurenine, N'-acetyl-kynurenine, and 6-chloro-kynurenine), galactitol, litesse, ligicane, lycacin, ragdunem, guanidine, phalernum, mavinrin I, mavinrin II, maltol, multisorb, maltodextrin, maltotriol, mannosamine, miraculin, starch syrup, mogrosides (e.g., mogroside IV, mogroside V, and neomogroside), muclodiol, nanosugar, nari Ngin dihydrochalcone, neohesperidin dihydrochalcone, nib sugar, nigero-oligosaccharide, norbu, orgate syrup, osradin, pekmez, pentadine, periandrin I, perillaldehyde, perillartin, Gynostemma pentaphyllum, phenylalanine, flomisoside I, florozidine, phyllodulcin, polyglycitol syrup, polypodoside A, pterocarioside A, pterocarioside B, Reviana, refiner syrup, rub syrup, rubsoside, serigeine A, shugr, siamenoside I, monk fruit (siraitia)This may include, but is not limited to, natural or synthetic sweeteners such as grosvenorii, soy oligosaccharides, Splenda, SRI oxime V, steviol glycoside, steviol bioside, stevioside, strozin 1, 2 and 4, sucronic acid, sucrononate, sugar, sucrose, phlorizin, super aspartame, tetrasaccharides, treitol, molasses, trilobtain, tryptophan and its derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, boremitol, birch sap, aspartame-acesulfame, asgurin, and any combination or blend of two or more of these.

[0057] Additional sweeteners may also include combinations of any two or more of the aforementioned sweeteners. In some embodiments, the sweetener may include combinations of two, three, four, or five of the 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 may be a calorie sweetener such as sucrose, fructose, xylitol, erythritol, or a combination thereof. In some embodiments, the ingestible composition may not contain (or may substantially not contain in some embodiments) stevia-derived sweeteners, such as steviol glycosides, glucosylated steviol glycosides, or rebaudiosides.

[0058] In some embodiments, the sweetener is sucrose. In some other embodiments, the sweetener is steviol glycoside.

[0059] In some embodiments, the ingestible composition contains acidic substances such as organic acids. Non-limiting examples of such organic acids include acetic acid, malonic acid, citric acid, lactic acid, and the like.

[0060] In certain embodiments, the ingestible composition may include any additional ingredients or combinations of ingredients commonly used in food and beverage products, including: Acids, such as citric acid, phosphoric acid, ascorbic acid, sodium sulfate, lactic acid, or tartaric acid; Bitter components, such as caffeine, quinine, green tea, catechins, polyphenols, green robusta coffee extract, green coffee extract, potassium chloride, menthol, or proteins (e.g., proteins and protein isolates derived from plants, algae, or fungi); Colorants, such as caramel, red #40, yellow #5, yellow #6, blue #1, red #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, such as ascorbic acid, calcium disodium EDTA, α-tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol, or sodium hexametaphosphate; Vitamins or functional ingredients, such as resveratrol, CoQ10, omega-3 fatty acids, theanine, choline chloride (citocorin), fibersol, inulin (chicory root), taurine, ginseng extract, guana extract, ginger extract, L-phenylalanine, L-carnitine, L-tartrate, D-glucuronolactone, inositol, bioflavonoids, echinacea, ginkgo biloba, yerba mate, linseed oil, Garcinia cambogia peel extract, white tea extract, ribose, milk thistle (milk) Thistle extract, grape seed extract, pyridoxine hydrochloride (vitamin B6), cyanocobalamin (vitamin B12), niacinamide (vitamin B3), biotin, calcium lactate, calcium pantothenate (pantothenic acid), calcium phosphate, calcium carbonate, chromium chloride, chromium polynicotinate, cupric 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; Fogging agents, such as ester gums, brominated vegetable oils (BVO), or sucrose acetate isobutyrate (SAIB); Buffering agents, such as sodium citrate, potassium citrate, or salts; Flavors, for example, propylene glycol, ethyl alcohol, glycerin, gum arabic (acacia gum), maltodextrin, modified corn starch, dextrose, natural flavors, natural flavors with other natural flavors (natural flavors WONF), natural and artificial flavors, artificial flavors, silicon dioxide, magnesium carbonate, or tricalcium phosphate, or Starch and stabilizers, such as pectin, xanthan gum, carboxymethylcellulose (CMC), polysorbate 60, polysorbate 80, medium-chain triglycerides, cellulose gel, cellulose gum, sodium caseinate, processed food starch, gum arabic (acacia gum), inulin, or carrageenan. This includes, but is not limited to, these.

[0061] The ingestible compositions may have any suitable pH. In some embodiments, flavor-modifying compounds enhance the sweetness of sweeteners over a wide pH range, for example, from low to neutral pH. Low and neutral pH ranges include, but are not limited to, pH values ​​of 1.5–9.0, 2.5–8.5, 3.0–8.0, 3.5–7.5, and 4.0–7. In certain embodiments, the compounds disclosed and described herein, individually or in combination, can enhance the perceived sweetness of a fixed concentration of sweetener in taste tests at compound concentrations of 50 μM, 40 μM, 30 μM, 20 μM, or 10 μM in both low and neutral pH values. In certain embodiments, the enhancing factors of the compounds disclosed and described herein, individually or in combination, at low pH are substantially the same as those of the compounds at neutral pH. Such consistent sweetness-enhancing properties over a wide pH range enable the widespread use of the compounds disclosed and described herein, individually or in combination, in a wide variety of foods and beverages.

[0062] In some embodiments, the ingestible composition includes flavorings. Any suitable flavoring may be used. In some embodiments, the flavorings include synthetic flavor oils and flavorings, or oils, oleopolymers and extracts derived from plants, leaves, flowers, fruits, etc., or combinations thereof. Non-limiting examples of flavor oils include spearmint oil, cinnamon oil, wintergreen oil (methyl salicylate), peppermint oil, Japanese mint oil, clove oil, bay oil, anise oil, eucalyptus oil, thyme oil, cedar leaf oil, nutmeg oil, allspice, sage oil, mace oil, bitter almond oil, and cassia oil. Other non-exclusive examples of flavors include natural and synthetic fruit flavors such as vanilla, as well as citrus oils such as lemon, orange, lime, grapefruit, yaz, and sudachi, and fruit essences such as apple, pear, peach, grape, blueberry, strawberry, raspberry, cherry, plum, pineapple, watermelon, apricot, banana, melon, apricot, plum, cherry, raspberry, blackberry, tropical fruits, mango, mangosteen, pomegranate, and papaya.Other potential flavors include milk, butter, cheese, cream, and yogurt; vanilla; tea or coffee flavors, e.g., green tea, oolong tea, black tea, cocoa, chocolate, and coffee; mint flavors, e.g., peppermint, spearmint, and mint; spicy flavors, e.g., asafoetida, ajwain, anise, angelica, fennel, allspice, cinnamon, chamomile, mustard, cardamom, caraway, cumin, clove, pepper, coriander, sassafras, savory, sansho, shiso, juniper berry, ginger, star anise, horseradish, thyme, tarragon, dill, chili pepper, nutmeg, basil, marjoram, rosemary, bay leaf, and wasabi (Japanese) Flavorings include horseradish flavor; alcohol flavors, such as wine, whiskey, brandy, rum, gin, and liqueur flavors; floral flavors; and botanical flavors, such as onion, garlic, cabbage, carrot, celery, mushroom, and tomato flavors. These flavorings may be used in liquid or solid form, individually or in mixtures.In the context of dairy products or dairy-like products, the most commonly used flavoring agents are those that impart flavors, 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, Irish cream, white chocolate, raspberry, pumpkin pie spice, peppermint, or any combination thereof.

[0063] In some embodiments, the edible composition comprises vanillin or a vanillin analog that imparts a vanilla flavor to the flavoring agent. In some further embodiments, the edible composition comprises one or more lactones that impart a creamy flavor to the composition.

[0064] In some embodiments, the ingestible composition includes a yeast extract, such as a yeast lysate. Such an extract can be obtained from any suitable yeast strain, provided that such an extract is suitable for consumption. Non-limiting examples of such yeasts include yeasts of the genus Saccharomyces, such as budding yeast (Saccharomyces cerevisiae) or brewer's yeast (Saccharomyces pastorianus); yeasts of the genus Candida, such as Torula yeast (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, such as Zygosaccharomyces mellis. In some embodiments, the yeast is collected after brewing beer, sake, etc. In some embodiments, the yeast is yeast that has been dried after collection (dried yeast).

[0065] Such extracts can be produced by any suitable means. Generally, yeast extracts or lysates are produced by extracting the contents of yeast cells from cell wall material. In many cases, intracellular digestive enzymes (or additional enzymes added to the composition) break down proteins and polynucleotides in yeast into amino acids, oligopeptides (e.g., 2-10 peptides), nucleotides, oligonucleotides (2-10 nucleotides), and mixtures thereof. Yeast lysates can be prepared by lysing yeast. For example, in some embodiments, cultured yeast is broken down or lysed by enzymatic decomposition, autolysis, alkaline extraction, hot water extraction, acid decomposition, sonication, homogenization, freeze-thaw, etc. (two or more of these may be used in combination) to obtain a yeast lysate. Yeast may be cultured by conventional methods. In some embodiments, cultured yeast is heat-treated and then treated with a lysing enzyme to obtain an enzymatic lysate. Heat treatment conditions are, for example, 80°C to 90°C for 5 to 30 minutes. Various enzymes can be used as lysis enzymes in enzymatic hydrolysis, as long as they can dissolve the yeast cell wall. The reaction conditions may be set to be optimal or suitable for the lysis enzyme used, and specific examples may 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 may be, for example, 3 to 5 hours.

[0066] Compositions containing yeast lysate can be obtained from various commercial sources. For example, in some embodiments, the yeast lysate is provided by a flavoring additive marketed under the name MODUMAX (DSM Food Specialties BV, Delft, Netherlands).

[0067] In some embodiments, the ingestible composition includes a sweetener. Any suitable sweetener may be used in the ingestible compositions disclosed herein, including synthetic sweeteners, natural sweeteners, or any combination thereof.

[0068] Examples of suitable synthetic sweeteners include, but are not limited to, N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazine-5-yl)oxy)-2-methylpropan-2-yl)isonicotinamide or any ingestible salt thereof, 3-hydroxybenzoic acid, or any compound described in U.S. Patent Nos. 8,541,421, 8,815,956, 9,834,544, 8,592,592, 8,877,922, 9,000,054, and 9,000,051, as well as U.S. Patent Application Publication No. 2017 / 0119032.

[0069] Suitable examples of natural sweeteners include, but are not limited to, hesperetin dihydrochalcone, hesperetin dihydrochalcone-4'-O'glucoside, neohesperetin dihydrochalcone, blazein, hesperidin, phyllodultin, naringenin, naringin, phloretin, glucosylated steviol glycoside, (2R,3R)-3-acetoxy-5,7,4'-trihydroxyflavanone, (2R,3R)-3-acetoxy-5,7,3'-trihydroxy-4'-methoxyflavanone, rubusoside, thaumatin, monellin, miraculin, glycyrrhizin and their ingestible salts (e.g., mono-ammonium salts), naringin dihydrochalcone, myricetin, nobiletin, polymethoxyflavones, mixed methoxy- and hydroxyflavones, quercetin, and certain amino acids. As used herein, the term "glucosylated steviol glycoside" refers to a product in which a natural steviol glycoside compound is enzymatically glucosylated. Glucosylation generally occurs through glycosidic bonds, such as α-1,2, α-1,4, α-1,6, β-1,2, β-1,4, and β-1,6 bonds.

[0070] 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]thiadiazine-5-yl)oxy)-2,2-dimethyl-N-propyl-propanamide, N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]-thiadiazine-5-yl)oxy)-2-methyl-propan-2-yl)isonicotinamide, or an ingestible salt thereof. In some embodiments, the ingestible composition comprises N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazine-5-yl)oxy)-2-methyl-propan-2-yl)isonicotinamide, or an ingestible salt thereof. In some embodiments, the ingestible composition includes N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazine-5-yl)oxy)-2-methyl-propane-2-yl)isonicotinamide.

[0071] In some embodiments, the ingestible composition contains one or more umami-enhancing compounds. Such umami-enhancing compounds include, but are not limited to, naturally occurring or synthetic compounds, such as any compounds described in U.S. Patent Nos. 8,735,081, 8,124,121, and 8,968,708. In some embodiments, the umami-enhancing compound is (2R,4R)-1,2,4-trihydroxyheptadeca-16-ene, (2R,4R)-1,2,4-trihydroxyheptadeca-16-yin, 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]dioxol-5-carboxamide.

[0072] In some further embodiments, the ingestible composition comprises one or more cooling-enhancing compounds. Such cooling-enhancing compounds include, but are not limited to, naturally occurring compounds such as menthol or its analogues, or synthetic compounds such as any compounds described in U.S. Patent No. 9,394,287 and No. 10,421,727. Non-limiting examples include N-ethyl-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide, N-(1H-pyrazole-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide, 2-(4-fluorophenoxy)-N-(1H-pyrazole-3-yl)-N-(thiophen-2-ylmethyl)acetamide, 2-(2-hydroxy-4-methylphenoxy)-N-(1H-pyrazole-3-yl)-N-(thiophen-2-ylmethyl)acetamide, 2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-(1 Examples include H-pyrazole-3-yl)-N-(thiophen-2-ylmethyl)-acetamide, 2-((2,3-dihydro-1H-inden-5-yl)oxy)-N-(1H-pyrazole-3-yl)-N-(thiazole-5-ylmethyl)-acetamide, 2-((5-methoxybenzofuran-2-yl)oxy)-N-(1H-pyrazole-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.

[0073] 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 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-dimethylisoxazole-4-yl)-methyl)-1H-pyrazole-4-yl)-1-(3-hydroxybenzyl)-imidazolidin-2,4-dione, 4-(2,2,3-trimethylcyclopentyl)butanoic acid, 3β-hydroxydihydrocostunolide, 3β-hydroxyperenolide, probenecid, sakuranetin, 6-methoxysakuranetin, jaseocidine, 4'-fluoro-6-methoxyflavonone, 6,3'-dimethoxyflavonone, 6-methoxyflavonone, γ-aminobutyric acid, Nα,Nα-bis(carbomethyl)-L-lysine, ( (+ / -) Abscisic acid, sodium gluconate, monosodium glutamate, sodium acetate, homoeriodictiol, stervin, eriodictiol, 2,4,dihydrobenzoic acid, neodiosmin, 1-carboxymethyl-5-hydroxy-2-hydroxymethylpyridinium, flavan-3-spiro-C-glycoside, poly-γ-glutamic acid, α,α-trehalose, taurine, (2)-gingerdione, 2,4,-dihydroxybenzoic acid, L-theanine, enterodiol, lariciresinol, enterolactone, matairesinol, and any combination thereof.

[0074] In some further embodiments, the ingestible composition comprises one or more acidity-modifying compounds.

[0075] In some further embodiments, the ingestible composition comprises one or more mouthfeel-modifying compounds. Examples of such mouthfeel-modifying compounds include, but are not limited to, tannins, cellulose materials, and bamboo powder.

[0076] In some further embodiments, the ingestible composition comprises one or more flavor-masking compounds. Such flavor-masking compounds include, but are not limited to, cellulose materials, materials extracted from fungi, materials extracted from plants, citric acid, carbonic acid (or carbonates), and the like.

[0077] Flavored products In certain embodiments, the Disclosure provides a flavored product comprising an edible composition of any of the embodiments described above. 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, toothpaste, whitening agent, etc.

[0078] In embodiments where the flavored product is a beverage, the beverage may be selected from the group consisting of fortified 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 beverages, nectar, vegetable juice, vegetable-flavored juice, sports drinks, energy drinks, fortified water beverages, vitamin-fortified water, near-water beverages, coconut water, tea-type beverages, coffee, cocoa beverages, milk-containing beverages, cereal extract-containing beverages, and smoothies. In some embodiments, the beverage may be a soft drink.

[0079] In any aspect and specific embodiment of any embodiment described herein that refers to a flavored product, the flavored product is a non-natural product, such as a packaged food or beverage product.

[0080] Further non-limiting examples of food and beverage products or formulations include sweet coatings, sugar glazes or sugar syrups for such products or any entities, which fall under the categories of soups, dried processed foods, beverages, ready meals, canned or preserved foods, frozen processed foods, chilled processed foods, snack foods, baked goods, confectionery, dairy products, ice cream, meal replacements, pasta and noodles, and sauces, dressings and condiments, baby food, and / or spreads.

[0081] Generally, the soup category refers to canned / preserved, dried, instant, refrigerated, UHT, and frozen soups. For the purposes of this definition, soup means a food prepared in a liquid, made from meat, poultry, fish, vegetables, grains, fruits, and other ingredients, and which may contain visible fragments of some or all of these ingredients. It may be clear (as a broth) or thick (as a chowder), smooth, pureed or chunky, ready to drink, semi-condensed or condensed, hot or cold, served as an appetizer, as a main course of a meal, or as a snack (sipped like a drink). Soups can be used as ingredients to prepare other food components and can range from broths (consommé) to sauces (cream or cheese-based soups).

[0082] The dried and prepared foods category typically means: (i) cooking aids, e.g., powders, granules, pastes, concentrated liquid products, e.g., concentrated bouillon, pressed cubes, tablets, or bouillon and bouillon-like products in powder or granular form (these are sold individually as finished products or as ingredients in products), sauces and recipe mixes (regardless of technology); (ii) meal solutions, e.g., dried and freeze-dried soups, e.g., dried soup mixes, dried instant soups, dried cooked soups, dried or shelf-stable cooked ready-made meals, meals and single-serving main dishes, e.g., pasta, potato and rice dishes; and (iii) food decoration products, e.g., seasonings, marinades, salad dressings, salad toppings, dips, breadcrumbs, batter mixes, shelf-stable spreads, barbecue sauces, liquid recipe mixes, concentrates, sauces or sauce mixes, e.g., salad recipe mixes (whether dried, liquid or frozen, sold as finished products or as ingredients in products).

[0083] The beverage category generally means beverages, beverage mixes and concentrates, and includes, but is not limited to, carbonated and non-carbonated beverages, alcoholic and non-alcoholic beverages, ready-to-drink beverages, liquid concentrates for making beverages such as soda, and dry powder beverage precursor mixes. The beverage category also includes alcoholic beverages, soft drinks, sports drinks, isotonic beverages, and hot drinks. Alcoholic beverages include, but are not limited to, beer, cider / berry, FAB, wine, and spirits. Soft drinks include carbonated beverages, e.g., cola and non-cola carbonated beverages; fruit juices, e.g., juices, nectars, juice drinks and fruit-flavored beverages; bottled water, including carbonated water, spring water and purified / table water; functional beverages (carbonated or non-carbonated beverages, including sports drinks, energy drinks or elixir drinks); and concentrates, e.g., liquid and powder concentrates in ready-to-drink quantities, but are not limited to these. Hot or cold beverages include, but are not limited to, coffee or iced coffee, such as fresh coffee, instant coffee, and blended coffee; tea or iced tea, such as black tea, green tea, white tea, oolong tea, and flavored tea; and other beverages, such as beverages in which flavor-based, malt-based, or plant-based powders, granules, blocks, or tablets are mixed with milk or water.

[0084] The snack food category generally refers to any food that can serve as a light snack, including, but is not limited to, sweet and flavored snacks and snack bars. Examples of snack foods include, but are not limited to, fruit snacks, chips / crisps, extruded snacks, tortillas / corn chips, popcorn, pretzels, nuts, and other sweet and flavored snacks. Examples of snack bars include, but are not limited to, granola / muesli bars, breakfast bars, energy bars, fruit bars, and other snack bars.

[0085] The baked goods category generally refers to any edible product manufactured using a method that involves exposure to heat or excessive sunlight. Examples of baked goods include, but are not limited to, bread, rolls, cookies, muffins, cereals, toaster pastries, pastries, waffles, tortillas, biscuits, pies, bagels, tarts, quiches, cakes, and any baked food, as well as any combination thereof.

[0086] The ice cream category generally refers to frozen desserts containing cream, sugar, and flavorings. Examples of ice cream include, but are not limited to, impulse ice cream; takeaway ice cream; frozen yogurt and artisan ice cream; and ice cream based on soy, oats, beans (e.g., adzuki beans and mung beans), and rice.

[0087] The category of confectionery generally refers to sweet edible products. Examples of confectionery include, but are not limited to, candies, gelatin, chocolate confectionery, sugar candies, gum, and any combination of these.

[0088] The meal replacement category generally refers to any food product intended to replace a regular meal, particularly for people with health or fitness concerns. Examples of meal replacements include, but are not limited to, weight loss products and recovery products.

[0089] 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 in which manufacturers have added recipe "techniques," resulting in a high degree of readyness, completeness, and convenience. Examples of ready meals include, but are not limited to, canned / preserved, frozen, dried, and refrigerated ready meals; dinner mixes; frozen pizzas; refrigerated pizzas; and prepared salads.

[0090] The pasta and noodle category includes canned, dried, and chilled / fresh pasta; and pasta and / or noodles including, but not limited to, plain noodles, instant noodles, chilled noodles, frozen noodles, and snack noodles.

[0091] The canned / preserved food category includes, but is not limited to, canned / preserved meats and meat products, fish / seafood, vegetables, tomatoes, beans, fruits, ready meals, soups, pasta, and other canned / preserved foods.

[0092] The frozen processed foods category includes, but is not limited to, frozen processed red meat, processed chicken, processed fish / seafood, processed vegetables, meat substitutes, processed potatoes, bakery products, desserts, ready meals, pizzas, soups, noodles, and other frozen foods.

[0093] The dried processed foods category includes, but is not limited to, rice, dessert mixes, dried ready meals, dried soups, instant soups, dried pasta, plain noodles, and instant noodles. The chilled processed foods category includes, but is not limited to, chilled processed meats, processed fish / seafood, lunch kits, fresh cut fruit, ready meals, pizzas, cooked salads, soups, fresh pasta, and noodles.

[0094] The Sauces, Dressings and Condiments category includes, but is not limited to, tomato pastes and purees, bouillon / stock cubes, herbs and spices, monosodium glutamate (MSG), table sauces, soy-based sauces, pasta sauces, wet sauces / cooking sauces, dry sauces / powder mixes, ketchup, mayonnaise, mustard, salad dressings, vinaigrettes, dips, pickles, and other sauces, dressings and condiments.

[0095] The baby food category includes, but is not limited to, formula milk or soy-based formulas, and cooked, dried, and other baby foods.

[0096] The spread category includes, but is not limited to, jams and preserves, honey, chocolate spreads, nut-based spreads, and yeast-based spreads.

[0097] The dairy category generally refers to edible products produced from the milk of mammals. Examples of dairy products include, but are not limited to, drinking milk, cheese, yogurt, and fermented milk beverages, as well as other dairy products.

[0098] Additional examples of flavored products, particularly food and beverage products or formulations, are provided below. Exemplary edible compositions include one or more confections, chocolate confections, tablets, countlines, selflines / softlines in bags, boxed assortments, standard boxed assortments, twist-wrapped miniatures, seasonal chocolates, chocolates with toys, alfajores, other chocolate confections, mints, standard mints, power mints, boiled confections. Sweets, lozenges, gum, jelly, and chews, toffee, caramel and nougat, medicinal candies, lollipops, licorice, other sugar candies, bread, packaged / factory bread, unpackaged / artisan bread, pastries, cakes, packaged / factory cakes, unpackaged / artisan cakes, cookies, chocolate coated biscuits, sandwich biscuits, filled biscuits, flavored biscuits and crackers, bread substitutes, breakfast cereals, RTE cereals, family breakfast cereals, flakes, muesli, other cereals, kids' breakfast cereals, hot cereals, ice cream, impulse ice cream, single serving dairy ice cream, single serving water ice cream, multipack dairy ice cream, multipack water ice cream, takeaway ice cream, takeaway dairy ice cream, ice cream Cream desserts, bulk ice cream, takeaway water ice cream, frozen yogurt, artisan ice cream, dairy products, milk, raw milk / pasteurized milk, whole fat raw milk / pasteurized milk, semi-skimmed raw milk / pasteurized milk, long-life milk / UHT milk, whole fat long-life milk / UHT milk, semi-skimmed long-life milk / UHT milk, non-fat long-life milk / UHT milk, goat's milk, condensed milk / unsweetened condensed milk, plain condensed milk / unsweetened condensed milk, flavored condensed milk, functional condensed milk and other condensed milk, flavored milk beverages, dairy-only flavored milk beverages, fruit juice flavored milk beverages, soy milk, fermented milk beverages, fermented dairy beverages, coffee whitener, powdered milk, flavored powdered milk beverages, cream, cheese, processed cheese, spreadable processed cheese, non-spreadable processed cheese, non-processed cheese,Spreadable unprocessed cheese, hard cheese, packaged hard cheese, unpackaged hard cheese, yogurt, plain / natural yogurt, flavored yogurt, fruit yogurt, probiotic yogurt, drinking yogurt, regular drinking yogurt, probiotic drinking yogurt, refrigerated shelf-stable desserts, dairy-based desserts, soy-based desserts, refrigerated snacks, fromage frais and quark, plain fromage frais and quark, flavored fromage frais and quark, savory fromage frais and quark, sweet and flavored snacks, fruit snacks, chips / crisps, extruded snacks, tortilla / corn chips, popcorn, pretzels, nuts, other sweet and flavored snacks, snack bars, granola bars, breakfast bars, energy bars, fruit bars, other snack bars, meal replacement products, weight loss products, recovery beverages, ready meals, canned ready meals, frozen ready meals, dried ready meals, refrigerated ready meals, dinner mixes, frozen pizzas, refrigerated pizzas, soups Canned soups, dried soups, instant soups, chilled soups, hot soups, frozen soups, pasta, canned pasta, dried pasta, chilled / fresh pasta, noodles, plain noodles, instant noodles, instant noodles in cups / bowls, instant noodles in pouches, chilled noodles, snack noodles, canned foods, canned meat and meat products, canned fish / seafood, canned vegetables, canned tomatoes, canned beans, canned fruit, canned ready meals, canned soups, canned pasta, other canned foods, frozen foods, frozen processed red meat, frozen processed chicken, frozen processed fish / seafood, frozen processed vegetables, frozen meat substitutes, frozen potatoes, oven-baked Baked potato chips, other oven-baked potato products, uncooked frozen potatoes, frozen bakery products, frozen desserts, frozen ready meals, frozen pizza, frozen soup, frozen noodles, other frozen foods, dried foods, dessert mixes, dried ready meals, dried soup, instant soup, dried pasta, plain noodles, instant noodles, instant noodles in cups / bowls, instant noodles in pouches, 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 soup,This includes chilled / fresh pasta, chilled noodles, oils and fats, olive oil, vegetable oils and seed oils, cooking fats, butter, margarine, spreadable oils and fats, functional spreadable oils and fats, sauces, dressings and condiments, tomato paste and puree, bouillon / stock cubes, stock cubes, meat juice granules, liquid stocks and stocks, herbs and spices, fermented sauces, soy sauce, pasta sauces, wet sauces, dry sauces / powder mixes, ketchup, mayonnaise, regular mayonnaise, mustard, salad dressings, regular salad dressings, low-fat salad dressings, vinaigrette sauces, dips, pickles, other sauces, dressings and condiments, baby food, formula, standard formula, follow-up formula, infant formula, hypoallergenic formula, cooked baby food, dried baby food, other baby food, spreads, jams and preserves, honey, chocolate spread, nut-based spreads, and yeast-based spreads. Exemplary edible compositions also include confectionery, bakery products, ice cream, dairy products, sweet and flavored snacks, snack bars, meal replacement products, ready meals, soups, pasta, noodles, canned foods, frozen foods, dried foods, chilled foods, oils and fats, baby food, or spreads, or mixtures thereof. Exemplary edible compositions also include solid or liquid concentrated compositions for preparing breakfast cereals, sweetened beverages, or beverages, ideally allowing for a reduction in the concentration of conventionally known sugar sweeteners or artificial sweeteners.

[0099] Some embodiments provide chewable compositions that may or may not be intended to be swallowed. In some embodiments, the chewable composition may be a gum, chewing gum, sweetened gum, unsweetened gum, functional gum, or bubble gum, comprising the compounds disclosed and described herein individually or in combination.

[0100] Typically, an edible sweet-flavor modified composition will be judged by humans or animals through procedures generally known in the art, or, in the case of formulation tests, by a majority of a panel of at least eight human taste testers, to have increased sweetness compared to an edible composition prepared without the compounds of the present invention, by adding at least one of the compounds of the present invention in the presence of a sweetener,

[0101] In some embodiments, the compounds disclosed and described herein, individually or in combination, modulate the sweetness or other taste properties of other natural or synthetic sweeteners and edible compositions produced therefrom. In one embodiment, the compounds disclosed and described herein, individually or in combination, may be used or provided at their ligand-enhancing concentrations. For example, the compounds disclosed and described herein, individually or in combination, may exist in amounts from 0.001 ppm to 100 ppm, or in narrower alternative ranges of 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.

[0102] In some embodiments, the edible compositions disclosed herein may be provided individually or in combination in flavor concentrate formulations suitable for subsequent processing to produce, for example, ready-to-use (i.e., ready-to-serve) products. “Flavor concentrate formulation” means a formulation to be reconstituted with one or more diluents to become a ready-to-use composition. The term “ready-to-use composition” is used herein interchangeably with “edible composition,” and means any substance that can be ingested orally, alone or in combination with another substance, whether intended for ingestion or not. In one embodiment, a ready-to-use composition includes a composition that can be consumed directly by a human or animal. Flavor concentrate formulations are typically used by mixing or diluting them with one or more diluents, such as any edible or edible ingredient or product, to impart or adjust one or more flavors to the diluents. Such a use process is often referred to as reconstitution. Reconstitution can be carried out in both home and industrial settings. For example, a frozen fruit juice concentrate can be reconstituted in a kitchen by a consumer with water or other aqueous medium 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. Flavor concentrates have a higher concentration of flavorings or flavor modifiers than ready-to-use compositions, and therefore are generally not suitable for direct consumption without reconstitution. There are many advantages to the use and manufacture of flavor concentrates. For example, one advantage is that flavor concentrates can be reconstituted at the time of use by adding a suitable solvent, solid or liquid, thus reducing their weight and volume for transport.

[0103] Furthermore, in certain embodiments, the flavored product described in any of the embodiments above may include one or more additional flavor-modifying compounds, such as compounds that enhance sweetness (e.g., hesperetin, naringenin, glucosylated steviol glycoside, etc.), compounds that block bitterness, compounds that enhance umami, compounds that reduce sourness, compounds that enhance saltiness, compounds that enhance cooling effect, or any combination thereof.

[0104] In any aspect and specific embodiment of the embodiments described herein that refer to sweetener or flavor concentrates, the sweetener or flavor concentrate is a composition specifically manufactured for the production of a product that does not exist in nature, such as a flavored product, such as a food or beverage product.

[0105] In one embodiment, the flavor concentrate formulation comprises i) the compounds disclosed and described herein, individually or in combination; ii) a carrier; and iii) optionally at least one auxiliary agent. The term “carrier” typically refers to an inert adjunct, such as a solvent, binder, or other inert medium, used in combination with the compounds of the present invention and one or more optional auxiliary agents to form the formulation. For example, water or starch may be a carrier for the flavor concentrate formulation. In some embodiments, the carrier is the same as the diluent medium for reconstituting the flavor concentrate formulation, and in other embodiments, the carrier is different from the diluent medium. As used herein, the term “carrier” includes, but is not limited to, an ingestible carrier.

[0106] The term "auxiliary agent" 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, at least one auxiliary agent comprises one or more flavoring agents. The flavoring agents may be any flavor known to those skilled in the art or to consumers, such as chocolate, coffee, tea, mocha, French vanilla, peanut butter, chai, or a combination thereof. In another embodiment, at least one auxiliary agent comprises one or more sweeteners. The one or more sweeteners may be any of the sweeteners described in this application. In another embodiment, at least one auxiliary agent comprises one or more components 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. Patent No. 6,468,576, the contents of which are incorporated herein by reference in whole for all purposes.

[0107] In one embodiment, the flavor concentrate formulation of the present invention may be in a form selected from the group consisting of liquids including solutions and suspensions, solids, foamy substances, pastes, gels, creams, and combinations thereof, for example, a liquid 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 bases. In some embodiments, the flavor concentrate formulation of the present invention may be carbonated or non-carbonated.

[0108] Flavoring concentrates may further contain at least one adjuvant: a freezing point depressant, a nucleating agent, or both. A freezing point depressant is an ingestible compound or agent that can lower 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 a freezing point depressant. In addition to inhibiting the onset of freezing, freezing point depressants can also reduce the water activity of the flavoring concentrate. Examples of freezing point depressants include, but are not limited to, carbohydrates, oils, ethyl alcohol, polyols, e.g., glycerol, and combinations thereof. A nucleating agent refers to an ingestible compound or agent that can promote nucleation. The presence of a nucleating agent in a flavoring concentrate can improve the mouthfeel of a frozen slush and help maintain the physical properties and performance of the slush at freezing temperatures by increasing the number of desired ice crystallization centers. Examples of nucleating agents include, but are not limited to, calcium silicate, calcium carbonate, titanium dioxide, and combinations thereof.

[0109] In one embodiment, the flavor concentrate is formulated to have a low water activity in order to extend its 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 has a water activity of less than about 0.85. In another embodiment, the flavor concentrate has a water activity of less than about 0.80. In yet another embodiment, the flavor concentrate has a water activity of less than about 0.75.

[0110] In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least twice the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least five times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least ten times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least fifteen times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least twenty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least thirty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least forty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least fifty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate contains the compound of the present invention at a concentration at least 60 times the concentration of the compound in the ready-to-use composition. In another embodiment, the flavor concentrate contains the compound of the present invention at a concentration up to 100 times the concentration of the compound in the ready-to-use composition.

[0111] In some embodiments, flavorings may be used in many distinct physical forms known in the art to provide an initial burst of flavor and / or a sustained sensation of flavor. Without limiting these, such physical forms include free forms, e.g., spray-dried forms, powder forms, bead forms, encapsulated forms, and mixtures thereof.

[0112] In some embodiments, the ingestible composition comprises a flavoring compound and a bulking agent according to any of the embodiments described above. Suitable bulking agents include, but are not limited to, maltodextrin (10DE, 18DE, or 5DE), corn syrup solids (20 or 36DE), sucrose, fructose, glucose, invert sugar, sorbitol, xylose, ribose, mannose, xylitol, mannitol, galactitol, erythritol, maltitol, lactitol, isomalt, maltose, tagatose, lactose, inulin, glycerol, propylene glycol, polyols, polydextrose, fructooligosaccharides, cellulose and cellulose derivatives, 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 because they provide good uniformity of contents without adding significant calories.

[0113] In one embodiment, at least one bulking agent may be a bulking agent described in U.S. Patent No. 8,993,027.

[0114] In one embodiment, at least one bulking agent may be a bulking agent described in U.S. Patent No. 6,607,771.

[0115] In one embodiment, at least one bulking agent may be a bulking agent described in U.S. Patent No. 6,932,982.

[0116] In some embodiments, the tabletop sweetener composition may further include at least one anti-caking agent. As used herein, the terms “anti-caking agent” and “flow agent” refer to any composition that prevents, reduces, inhibits, or suppresses at least one sweetener from adhering to, binding to, or coming into contact with another sweetener molecule. Alternatively, an anti-caking agent may refer to any composition that aids in the uniformity and uniform dissolution of the contents. Non-limiting examples of anti-caking agents include 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.

[0117] In some embodiments, the sweetener compositions of any of the aforementioned embodiments are encapsulated using typical means for encapsulating flavor or fragrance compounds. Non-limiting examples of such techniques are U.S. Patent Application Publications 2016 / 0235102, 2019 / 0082727, 2018 / 0369777, 2018 / 0103667, 2016 / 0346752, 2015 / 0164117, 2014 / 0056836, 2012 / 0027866, 2010 / 0172945, and This is described in U.S. Patent No. 2007 / 0128234, as well as U.S. Patents No. 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 aforementioned patent publications and patents are incorporated herein by reference as if they were described in their entirety herein.

[0118] Non-animal protein materials and products manufactured therefrom Products intended to replace or substitute meat or dairy products often rely on starches and proteins derived from various non-animal-based materials, such as plants, algae, fungi, or combinations thereof, to mimic the texture and flavor of meat or dairy products. Non-exclusive examples of non-animal-based proteins include plant proteins such as pea protein, soy protein, almond protein, cashew protein, canola protein, chickpea protein, broad bean protein, sunflower protein, wheat protein, oat protein, barley protein, potato protein, and combinations thereof. Due to compositional differences between such plant-based materials and animal-derived materials, such as the lack of glutamate-containing proteins and glutathione, these products may lack the umami or richness that consumers traditionally associate with meat or dairy products, or they may have a bitterness not found in animal proteins.

[0119] Accordingly, in certain embodiments, the Disclosure provides a flavored product comprising a plant-based material (e.g., plant-based starch, plant-based protein, or a combination thereof) according to any of the embodiments described above and a zinc salt. In some further embodiments, the flavored product may include any combination of the features described above for an edible composition comprising a zinc salt. In some embodiments, the flavored product is a beverage, e.g., soy milk, almond milk, rice milk, oat milk, protein drink, meal replacement drink, or other similar product. In some other embodiments, the flavored product is a meat substitute product, e.g., a plant-based chicken product (e.g., plant-based chicken nuggets), a plant-based beef product (e.g., a plant-based burger), etc. In some other embodiments, the flavored product is a protein powder, a meal replacement powder, a plant-based creamer for coffee or tea, etc. In certain further embodiments, such a product comprises additional ingredients and has additional features, as is typically used in the preparation and / or manufacture of such a product. For example, flavor modifiers can be combined with other flavor and taste modifiers according to techniques known in the relevant field, and can also be encapsulated in specific materials. Appropriate concentrations of flavor modifiers are described above.

[0120] In some embodiments, the flavored product contains one or more plant-based proteins that impart bitterness, which is at least partially reduced by using 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, potato protein, and combinations thereof.

[0121] In several alternative embodiments similar to those described above, algal or fungal proteins or starches are used instead. In some embodiments, these flavored products also include fibers that give the product texture. Suitable fibers 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 modifiers can be introduced in any suitable manner. In some embodiments, the flavor modifiers are incorporated together with other flavoring components into a flavor emulsion, such as a water-in-oil emulsion.

[0122] Non-meat protein materials and products made therefrom Certain non-meat animal proteins, such as milk proteins and proteins from bone broth, are commonly used in food products and are also marketed as the main component of certain protein powders. Such proteins can impart bitter flavors that consumers do not desire. This is particularly true for protein isolates, such as whey proteins, collagen proteins, and casein proteins. Therefore, this disclosure provides edible compositions comprising non-meat animal proteins and flavor-modifying compounds. The flavor-modifying compounds may be present in any suitable combination according to the embodiments described in the preceding sections of this disclosure. In some embodiments, the non-meat animal protein is bone protein, such as collagen protein, derived from the bones of animals, such as cattle, pigs, donkeys, horses, chickens, ducks, goats, geese, rabbits, lambs, sheep, buffaloes, ostriches, and camels. In some embodiments, the non-meat animal protein is milk protein, such as whey protein, casein protein, or any combination thereof. Milk can be the milk of any suitable animal, such as cows, donkeys, horses, sheep, buffaloes, camels, etc.

[0123] Furthermore, flavoring compounds may be present in certain food or beverage products containing animal milk or ingredients derived from animal milk. Examples of such products include cheese, cheese spread, yogurt, kefir, milk, processed dairy products, cottage cheese, sour cream, and butter.

[0124] Blocking the bitter taste of pharmaceutical APIs Many pharmaceutical compounds impart a bitter taste, thus limiting the methods by which they can be formulated and administered. Therefore, in certain embodiments, this disclosure provides pharmaceutical compositions comprising a bitter pharmaceutically active ingredient and a flavor-modifying compound. Such pharmaceutical compositions may be in any form suitable for oral administration, such as tablets, lozenges, capsules, powders, liquid solutions, liquid suspensions, etc. Such pharmaceutical compositions may include any suitable pharmaceutical excipients, binders, etc., such as those described in Remington's Pharmaceutical Sciences. In some embodiments, the bitter pharmaceutically active ingredient is an ion channel inhibitor, such as a proton channel inhibitor. Other examples of bitter APIs whose bitterness is reduced by flavor modifiers include, but are not limited to, atropine, brinzolamide, chloramphenicol, chloroquine, clindamycin, dexamethasone, digoxin, diltiazem, diphenhydramine, docusate, dorzolamide, doxepin, doxylamine, enalapril, erythromycin, esomeprazole, famotidine, gabapentin, gincolide A, guaifenesin, L-histidine, lomefloxacin, methylprednisolone, ofloxacin, oleuropein, oxyphenonium, pirenzepine, prednisone, ranitidine, trapidil, trimethoprim, and cetirizine.

[0125] Use in oral care products Oral care products often contain ingredients that impart an unpleasant astringent or bitter taste. Such ingredients include menthol, menthol analogues, mint extract, 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, and toothpastes. Such oral care products may also contain flavor-modifying compounds to block or mask the bitterness of such compounds. [Examples]

[0126] To further illustrate the present invention, the following examples are included. These examples should, of course, 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 present invention as described herein and claimed. Readers will recognize that those skilled in the art, with knowledge of this disclosure and the art in the art, can prepare and use the present invention without the need for exhaustive examples.

[0127] Example 1: Preparation of (2,3-trans)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-3-yl acetate (101) [ka]

[0128] A solution of flavanonol 1 (Example 1a, 1.0 g, 3.3 mmol) in AcOH (70 mL) was placed in a 250 mL pressure flask equipped with a stirring bar. The solution was degassed by vigorously bubbling N2 into the solution for 15 minutes. The headspace was spurged with N2, and the sealed solution was heated at 120 °C for 60 hours. The solvent was removed under reduced pressure, and the residue was partitioned between siRNA (100 mL) and brine (100 mL). The aqueous layer was extracted (2 × 100 mL siRNA), and the combined organic matter was dried over MgSO4, filtered, and concentrated. The crude residue was purified by preparative RP HPLC (10 → 90% MeCN / H2O) to obtain 290 mg (yield 25%) of 101 as a pale yellow oil.

[0129] [ka]

[0130] Example 1a: Preparation of (2,3-trans)-3,5-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-chroman-4-one (1) [ka]

[0131] In a 100 mL round-bottom flask equipped with a stirring bar and a condenser (air-cooled) rubber septum, epoxide 2 (Example 1b, 816 mg, 188 mmol) was added under N2, followed by dry methanolic HCl (1.25 M, 20 mL). The reaction mixture was heated at 55 °C for 2 hours, after which LC-MS analysis showed consumption of the starting material. The solvent was removed under reduced pressure, the residue was redissolved in MeOH (150 mL), and the solvent was removed under reduced pressure. The crude residue was purified by preparative RP HPLC (10 → 90% MeCN / H2O) to obtain 400 mg (yield 71%) of flavanonol 1 as a white solid.

[0132] [ka]

[0133] Example 1b: Preparation of (E)-1-(2,6-bis(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)propa-2-en-1-one (2) [ka]

[0134] An emulsion of chalcone 3 (Example 1c, 1.8 g, 4.4 mmol) in methanol (120 mL) was to be mixed with 530 mg (13 mmol) of NaOH at 22°C in a single addition, followed by the dropwise addition of an aqueous solution of hydrogen peroxide (30% by weight, 3.6 mL, 35 mmol). The reaction mixture was stirred for 18 hours, after which LC-MS analysis showed consumption of the starting materials. The reaction was quenched with saturated aqueous NH4Cl solution (120 mL) and extracted with HCl (3 × 100 mL). The organic matter was combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0 → 60% HCl / hexane) to obtain 1.36 g (72% yield) of chalcone epoxide 2 as a pale yellow oil.

[0135] [ka]

[0136] Example 1c: Preparation of (E)-1-(2,6-bis(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)propa-2-en-1-one (3) [ka]

[0137] To a solution of 4 (Example 1d, 3.50 g, 14.6 mmol) in methanol (40 mL), aqueous NaOH (30 wt%, 20 mL, 150 mmol) at 0°C was added. After stirring for 30 minutes, a solution of 5 (Example 1e, 3.44 g, 17.5 mmol) in MeOH (35 mL) was added dropwise. The reaction mixture was stirred for 20 hours (allowing the ice bath to melt), after which LC-MS analysis showed consumption of the starting material. The mixture was diluted with HCl (75 mL) and washed with saturated NH4Cl aqueous solution (2 × 75 mL). The aqueous layers were combined and extracted with (2 × 75 mL HCl). The organic layers were combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0 → 100% HCl / hexane) to obtain 5.70 g (yield 93%) of chalcone 3 as a yellow solid.

[0138] [ka]

[0139] Example 1d: Preparation of 1-(2,6-bis(methoxymethoxy)phenyl)ethane-1-one (4) [ka]

[0140] In an oven-dried 500 mL round-bottom flask equipped with a stirring bar and rubber septum, NaH (4.0 g, 60% dispersed mineral oil, 100 mmol), followed by anhydrous THF (80 mL), was added under N2. The suspension was cooled to 0°C in an ice bath, and a solution of 2',6'-dihydroxyacetophenone (S1, 5.0 g, 33 mmol) in THF (100 mL) was added dropwise over 15 minutes (the flask was vented with a 22 G needle to avoid overpressure). After stirring at 22°C for 20 minutes (to stop gas generation), the solution was cooled back to 0°C, and MOMCl (7.5 mL, 99 mmol) was added dropwise to the suspension at 0°C over 15 minutes. The reaction mixture was left to stir for 12 hours (to melt the ice bath), after which LC-MS analysis showed consumption of the starting materials. Ice water (150 mL) was slowly added, followed by extraction with SiO (3 × 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 → 40% siRNA / hexane) to obtain 5.6 g (70% yield) of acetophenone-4 as a colorless oil.

[0141] [ka]

[0142] Example 1e: Preparation of 4-methoxy-3-(methoxymethoxy)benzaldehyde (5) [ka]

[0143] In an oven-dried 1 L round-bottom flask equipped with a stirring bar and rubber septum, isovanillin (S2, 10 g, 66 mmol), followed by dry DCM (400 mL), was added under N2. The mixture was cooled to 0°C in an ice bath, and DIPEA (16 mL, 92 mmol) was slowly added. After stirring for 20 minutes, MOMCl (6.0 mL, 80 mmol) was added dropwise over 15 minutes at 0°C. The reaction mixture was left to stir for 18 hours (to melt the ice bath), after which LC-MS analysis showed consumption of the starting materials. Water (300 mL) was added, followed by extraction with DCM (3 × 150 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0 → 50% Depositphotos) to obtain compound 5 (12.7 g, yield 98%) as a white solid.

[0144] [ka]

[0145] Example 2: Preparation of (2,3-trans)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-3-ylpropionate (102) [ka]

[0146] Compound 102 (2.3 mg, yield 11%), which forms a transparent film, was prepared from 1 (Example 1a) and propionic acid as in Example 1.

[0147] [ka]

[0148] Example 3: Preparation of (2,3-trans)-7-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-3-yl acetate (103) [ka]

[0149] A solution of flavanonol 1B (Example 3a, 1.11 g, 3.67 mmol) in AcOH (85 mL) was placed in a 250 mL pressure flask equipped with a stirring bar. The solution was degassed by vigorously bubbling N2 into the solution for 15 minutes. The headspace was spurged with N2, and the sealed solution was heated at 120 °C for 60 hours. The solvent was removed under reduced pressure, and the residue was partitioned between siRNA (100 mL) and brine (100 mL). The aqueous layer was extracted (2 × 100 mL siRNA), and the combined organic matter was dried over MgSO4, filtered, and concentrated. The crude residue was purified by preparative RP HPLC (25 → 45% MeCN / H2O) to obtain 260 mg (yield 22%) of 103 as a pale yellow oil.

[0150] [ka]

[0151] Example 3a: Preparation of (2,3-trans)-3,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-chroman-4-one-methanol (1B) [ka]

[0152] In a 100 mL round-bottom flask equipped with a stirring bar and an air condenser, 2B (Example 3b, 2.3 g, 510 μmol), followed by dry methanolic HCl (1.25 M, 65 mL), was added under N2. The reaction mixture was heated at 55 °C for 6 hours, after which LC-MS analysis showed consumption of the starting material. The solvent was removed under reduced pressure, the residue was redissolved in MeOH (50 mL), and the solvent was removed under reduced pressure. The crude residue was purified by preparative RP HPLC (10 → 90% MeCN / H2O) to obtain 1.21 g (78% yield) of flavanonol 1B as a clear oil.

[0153] [ka]

[0154] Example 3b: Preparation of (E)-1-(2,6-bis(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)propa-2-en-1-one (2B) [ka]

[0155] An emulsion of chalcone 3B (Example 3c, 3.3 g, 7.9 mmol) in methanol (200 mL) was to be mixed with 950 mg (24 mmol) of NaOH at 22°C in a single addition, followed by the dropwise addition of an aqueous solution of hydrogen peroxide (30% by weight aqueous solution, 6.4 mL, 63 mmol). The reaction mixture was stirred for 15 hours, after which LC-MS analysis showed consumption of the starting material. The solvent was partially removed under vacuum, the mixture was diluted with MBTE (200 mL), washed with saturated aqueous NH4Cl solution (200 mL), and extracted with MBTE (2 × 150 mL). The organic matter was combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0 → 60% siRNA / hexane) to obtain 2.3 g (yield 67%) of chalcone epoxide 2B as a pale yellow oil.

[0156] [ka]

[0157] Example 3c: Preparation of (E)-1-(2,6-bis(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)propa-2-en-1-one (3B) [ka]

[0158] A solution of 4B (Example 3d, 2.0 g, 8.3 mmol) in methanol (30 mL) was mixed with aqueous NaOH (30 wt%, 6 mL, 42 mmol) at 0°C. After stirring for 30 minutes, a solution of MOM-isovanillin 5 (Example 1e, 1.8 g, 9.2 mmol) in MeOH (15 mL) was added dropwise. The reaction mixture was stirred for 45 hours (allowing the ice bath to melt), after which LC-MS analysis showed consumption of the starting material. The mixture was diluted with Et2O (50 mL) and washed with saturated NH4Cl aqueous solution (2 × 30 mL). The aqueous layers were combined and extracted with (2 × 40 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 → 60% siRNA / hexane) to obtain 2.8 g (80% yield) of chalcone 3B as yellow oil.

[0159] [ka]

[0160] Example 3d: Preparation of 1-(2,4-bis(methoxymethoxy)phenyl)ethane-1-one (4B) [ka]

[0161] In an oven-dried 500 mL round-bottom flask equipped with a stirring bar and rubber septum, NaH (4.10 g, 60% dispersed mineral oil, 103 mmol), followed by dry DCM (200 mL), was added under N2. The suspension was cooled to 0°C in an ice bath, and a solution of 2',4',-dihydroxyacetophenone S3 (4.46 g, 29.3 mmol) in DMF (10 mL) was added dropwise over 15 minutes (the flask was vented with a 22 G needle to avoid overpressure). After stirring for 25 minutes (to stop gas generation), MOMCl (5.12 mL, 67.4 mmol) was added dropwise to the suspension at 0°C over 5 minutes. The reaction mixture was left to stir for 19 hours (to melt the ice bath), after which LC-MS analysis showed consumption of the starting materials. Water (40 mL) was added, followed by extraction with DCM (3 × 100 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 → 40% siRNA / hexane) to obtain 5.9 g (84% yield) of acetophenone 4B as a clear oil.

[0162] [ka]

[0163] Example 4: Preparation of (2,3-trans)-7-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-3-ylpropionate (104) [ka]

[0164] A solution of 1D (Example 4a, 22 mg, 49 μmol) in MeOH (5 mL) was mixed with concentrated HCl (1 mL). The resulting solution was stirred at 22°C for 60 minutes, after which LC-MS analysis showed consumption of the starting material. The solvent was removed under reduced pressure, the residue was redissolved in MeOH (5 mL), and the solvent was removed under reduced pressure. The crude residue was purified by preparative RP HPLC (10 → 90% MeCN / H2O) to obtain 104 (10 mg, yield 59%) as a clear oil.

[0165] [ka]

[0166] Example 4a: Preparation of (2,3-trans)-2-(4-methoxy-3-(methoxymethoxy)phenyl)-7-(methoxymethoxy)-4-oxochroman-3-ylpropionate (1D) [ka]

[0167] To a solution of 2D (Example 4b, 20 mg, 51 μM) in DCM (3 mL), DMAP (13 mg, 110 μM), EDCI (21 mg, 110 μM), and then a solution of propionic acid (7.6 mg, 100 μM) in DCM (1 mL) were added. The resulting solution was stirred at 22°C for 18 hours, after which LC-MS analysis showed consumption of the starting material. The reaction mixture was directly loaded onto a silica column and purified by silica gel chromatography (0 → 50% ethyl acetate / hexane) to obtain 22 mg (96% yield) of ester 1D as a clear oil.

[0168] [ka]

[0169] Example 4b: Preparation of (2,3-trans)-3-hydroxy-2-(4-methoxy-3-(methoxymethoxy)-phenyl)-7-(methoxymethoxy)chroman-4-one (2D) [ka]

[0170] To a solution of 3D (Example 4c, 800 mg, 2 mmol) in dioxane (25 mL), Et2NH (1.1 mL, 11 mmol) was added under N2, followed by the slow addition of H2O2 (30 wt%, 6.6 mL, 64 mmol) over 15 minutes. The reaction mixture was left to stir vigorously for 18 hours, after which LC-MS analysis showed consumption of the starting material. The solution was cooled to 0°C on an ice bath, and a solution of Na2S2O3·5H2O (50 g, 0.28 mol) in H2O (approximately 150 mL) was slowly added over 30 minutes (caution: exothermic reaction!) to quench excess hydrogen peroxide, followed by extraction with siRNA (3 × 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% siRNA / hexane) to obtain 513 mg of compound 2D (yield 62%) as a white solid.

[0171] [ka]

[0172] Example 4c: Preparation of (E)-1-(2-hydroxy-4-(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)propa-2-en-1-one (3D) [ka]

[0173] To a solution of 4D (Example 4d, 740 mg, 3.8 mmol) in ethanol (20 mL), aqueous KOH (50 wt%, 5.4 mL, 75 mmol) was added, followed by the dropwise addition of compound 5 (Example 1e, 780 mg, 4.0 mmol) in EtOH (5 mL). The reaction mixture was stirred for 60 hours, after which LC-MS analysis showed consumption of the starting material. The mixture was diluted with Et2O (100 mL) and quenched with aqueous HCl (0.5 N, 100 mL). The aqueous layer was extracted with Et2O (3 × 100 mL). The etheric layers were combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0 → 40% siRNA / hexane) to obtain 0.8 g (yield 57%) of chalcone 3D as a yellow solid.

[0174] [ka]

[0175] Example 4d: Preparation of 1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)ethane-1-one (4D) [ka]

[0176] 2,4-dihydroxyacetophenone S3 (6.8 g, 45 mmol), followed by dried DCM (150 mL), was placed in an oven-dried 500 mL round-bottom flask equipped with a stirring bar and rubber septum under N2. DIPEA (14 mL, 80 mmol) was slowly added to the stirred suspension, resulting in a clear solution. MOMCl (4.1 mL, 54 mmol) was added dropwise to the stirred clear solution over 15 minutes. The reaction mixture was allowed to stir for 18 hours, after which LC-MS analysis showed consumption of the starting materials. The solvent was removed under reduced pressure, and the residue was purified by silica gel chromatography (0 → 40% siRNA / hexane) to obtain 8.5 g (97% yield) of acetophenone 4D as a yellow oil.

[0177] [ka]

[0178] Example 5: Preparation of (2,3-trans)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-3-ylpropionate-methanol (105) [ka]

[0179] To a solution of 1E (Example 5a, 15 mg, 30 μM) in DCM (2 mL), TiPS (10 μL) was added, followed by TFA (1 mL). The resulting solution was stirred at 22 °C for 40 minutes, after which LC-MS analysis showed consumption of the starting material. The solvent was removed under reduced pressure, and the residue was redissolved in MeOH (5 mL), and the solvent was removed under reduced pressure. The crude residue was purified by preparative RP HPLC (10 → 90% MeCN / H2O) to obtain 1.8 mg (yield 16%) of flavanonol 105 as a clear oil.

[0180] [ka]

[0181] Example 5a: Preparation of (2,3-trans)-2-(4-methoxy-3-(methoxymethoxy)phenyl)-5,7-bis(methoxymethoxy)-4-oxochroman-3-ylpropionate (1E) [ka]

[0182] To a solution of 2E (Example 5b, 14 mg, 31 μM) in DCM (3 mL), DMAP (7.6 mg, 62 μM), EDCI (12 mg, 62 μM), and then a solution of propionic acid (4.6 mg, 62 μM) in DCM (1 mL) were added. The resulting solution was stirred at 22°C for 18 hours, after which LC-MS analysis showed consumption of the starting materials. The reaction mixture was directly loaded onto a silica column and purified by silica gel chromatography (0 → 50% ethyl acetate / hexane) to obtain 15 mg (97% yield) of ester S20 as a clear oil.

[0183] [ka]

[0184] Example 5b: Preparation of (trans)-3-hydroxy-2-(4-methoxy-3-(methoxymethoxy)phenyl)-5,7-bis(methoxymethoxy)chroman-4-one (2E) [ka]

[0185] To an ice-cold (ice bath) solution of 3E (Example 5c, 3.77 g, 8.68 mmol) in dioxane (100 mL), Et2NH (4.5 mL, 43 mmol) was added under N2, followed by the slow addition of H2O2 (30 wt%). Upon adding approximately 85 mL of H2O2 solution, precipitation occurred, yielding 2E (557 mg, yield 14%) as a white solid.

[0186] [ka]

[0187] Example 5c: Preparation of (E)-1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)propa-2-en-1-one (3E) [ka]

[0188] 4E (Example 5d, 3.32 g, 13.0 mmol), KOH (50% by weight, 20 mL, 180 mmol), and 5 (Example 1e, 2.67 g, 13.6 mmol) in ethanol (60 mL) were prepared according to the procedure described in Example-1c to obtain 3E (5.5 g, yield 97%) as yellow oil. 22 H 27 O9[M+H] + The MS(ESI) calculated value was 435.2, and the measured value was 435.2.

[0189] Example 5d: Preparation of 1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)ethane-1-one (4E) [ka]

[0190] In an oven-dried 500 mL round-bottom flask equipped with a stirring bar and rubber septum, 2,4,6-trihydroxyacetophenone S4 (3.8 g, 23 mmol), followed by dried DCM (100 mL), was added under N2. The mixture was cooled to 0°C in an ice bath, and DIPEA (11 mL, 63 mmol) was slowly added. After stirring for 20 minutes, MOMCl (3.8 mL, 50 mmol) was added dropwise to the suspension at 0°C over 15 minutes. The reaction mixture was left to stir for 4 hours (allowing the ice bath to melt and the suspension to turn a light brown solution), after which LC-MS analysis showed consumption of the starting materials. Water (100 mL) was added, followed by extraction with DCM (3 × 75 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0 → 100% Â / hexane) to obtain 3.0 g (51% yield) of acetophenone 4E as a clear oil, which solidified upon standing.

[0191] [ka]

[0192] Example 6: Preparation of (2,3-trans)-5-hydroxy-2-(4-hydroxyphenyl)-4-oxochroman-3-yl acetate (106) [Chemical formula]

[0193] Into a 40 mL vial equipped with a magnetic stirrer and a Teflon cap, under N2, 1F (Example 6a, 190 mg, 0.48 mmol) was added, followed by a solution of Na2SO3 (180 mg, 1.4 mmol) in MeOH (6 mL) and H2O (6 mL). The resulting yellow solution was stirred at 28 °C for 18 hours, quenched with HCl (0.3 M, 6 mL), extracted with EtOAc (3 × 25 mL), the combined organics were dried over MgSO4, filtered, and concentrated. A small amount was purified by recrystallization from a MeCN-H2O mixture to give 4.2 mg (yield 3%) of 106 as a white solid.

[0194] [Chemical formula]

[0195] Example 6a: Preparation of (2,3-trans)-2-(4-acetoxyphenyl)-4-oxochroman-3,5-diyl diacetate (1F) [Chemical formula]

[0196] 1F (Example 6b, 234 mg, 745 μmol, as a 3:1 mixture of trans-cis isomers) was placed in a 200 mL round-bottomed vial equipped with a stir bar and a rubber septum, followed by dry DCM (40 mL). Anhydrous acetic acid (380 μL, 4.1 mmol) was added to the mixture, followed by DIPEA (860 μL, 5.2 mmol). After stirring for 5 minutes, a solution of DMAP (14 mg, 110 μmol) in DCM (3 mL) was added. The reaction was left stirring for 21 hours, after which LCMS analysis indicated consumption of the starting material. Water (40 mL) was added, followed by extraction with DCM (2 × 40 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. Preparative RP HPLC (10→90% MeCN / H2O) gave 233 mg (79% yield, 10:1 mixture trans:cis) of flavanonol triacetate 2F as a white solid. A small amount of the trans-cis mixture was purified to the pure trans-isomer by trituration with MeOH.

[0197] [Chemical formula]

[0198] Example 6b: Preparation of (2,3-trans)-3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one - methanol (1 / 1) (2E) [Chemical formula]

[0199] In a 40 mL round-bottom vial equipped with a stirring bar and a Teflon cap, 3F (Example 6c, 410 mg, 1.0 mmol), followed by dry methanolic HCl (1.25 M, 12 mL), was added under N2. The reaction mixture was heated at 55°C for 2 hours, after which LC-MS analysis showed consumption of the starting material. The solvent was removed under reduced pressure, the residue was redissolved 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) to obtain 234 mg (85% yield) of flavanonol 2F as a white solid (a mixture of trans and cis isomers in approximately a 3:1 ratio; epimerization may occur during the purification process). A small amount of the trans-cis mixture was purified to the pure trans isomer by trituration with MeOH.

[0200] [ka]

[0201] Example 6c: Preparation of (E)-1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)-3-(4-methoxy-3-(methoxymethoxy)phenyl)propa-2-en-1-one (3E) [ka]

[0202] A solution of chalcone 4F (Example 6d, 1.34 g, 3.45 mmol) in methanol (100 mL) was to be mixed with 0.4 g, 10 mmol of NaOH at 22°C in a single addition, followed by the dropwise addition of an aqueous solution of hydrogen peroxide (30% by weight, 2.8 mL, 28 mmol). The reaction mixture was stirred for 24 hours, after which LC-MS analysis showed the consumption of the starting materials. The reaction mixture was diluted with Et2O (75 mL), washed with saturated aqueous NH4Cl solution (2 × 75 mL), and extracted with Et2O (2 × 75 mL). The organic matter was combined, dried over MgSO4, filtered, and concentrated under reduced pressure to obtain 1.26 g (90% yield) of chalcone epoxide 3F as a pale yellow oil.

[0203]

Chem.

[0204] Example 6d: Preparation of (E)-1-(2,6-bis(methoxymethoxy)phenyl)-3-(4-(methoxymethoxy)phenyl)prop-2-en-1-one (4F)

Chem.

[0205] A solution of 4 (Example 1d, 0.94 g, 3.9 mmol) in methanol (10 mL) was added with aqueous NaOH (30 wt%, 5 mL, 35 mmol) at 22 °C, followed by a solution of 5A (Example 6e, 0.72 g, 4.3 mmol) in MeOH (7 mL). The reaction mixture was stirred for 18 h, and after that time, LCMS analysis indicated consumption of the starting material. The mixture was diluted with Et2O (50 mL) and washed with saturated aqueous NH4Cl (2 × 25 mL). The aqueous layers were combined and extracted with (2 × 50 mL Et2O). 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 / hexane) to afford 1.34 g (88% yield) of chalcone 4F as a pale yellow oil.

[0206] [[ID=​​​​​​​​​​​​​​​​​In an oven-dried 1 L round-bottom flask equipped with a stirring bar and rubber septum, 12 g, 98 mmol of 4-hydroxybenzaldehyde S5 was added under N2, followed by 250 mL of dried dimethyl phosphate (DCM). The mixture was cooled to 0°C in an ice bath, and 24 mL, 140 mmol of DIPEA was added, followed by 8.2 mL, 110 mmol of MOMCl (MOMCl) dropwise to the suspension at 0°C over 15 minutes. The reaction mixture was stirred for 18 hours (allowing the ice bath to melt), after which LC-MS analysis showed consumption of the starting materials. 100 mL of water was added, followed by extraction with 3 × 75 mL of DCM. The combined organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (0 → 50% Depositphotos) to obtain 15.7 g (96% yield) of aldehyde 5A as a clear oil.

[0209] [ka]

[0210] Example 7 - Compound Testing Compounds 101–106 were synthesized. The compounds were then tested in an in vitro cell-based assay using cells overexpressing the T1R sweet taste receptor. Sweetness dose-response curves were recorded, and the EC50 was determined. Table 2 summarizes the calculated EC50 values ​​for each test compound.

[0211] [Table 2]

[0212] Example 8 - Sensory evaluation: Sweetness alone Test samples were prepared from compound 101 (4 ppm aqueous solution) and compound 103 (7 ppm aqueous solution). Each test sample was evaluated by a sensory panel for its sweetness relative to a 1.5 wt% sucrose solution. Panelists were asked to select the sweeter sample from pairs of compound test samples and 1.5 wt% sucrose solutions. For compound 101, the taste sample was selected as "sweeter" 14 times out of a total of 60 times, while the control sucrose was selected 46 times. For compound 103, the taste sample was selected as "sweeter" 14 times out of a total of 69 times, while the control sucrose was selected 55 times.

[0213] Example 9 - Sensory evaluation: Enhancement Two control samples were prepared: one containing 6% by weight sucrose and the other 7.5% by weight sucrose in a low-sodium buffer. One test sample was prepared by adding 4 ppm of compound 101 to 6% by weight sucrose, and the other by adding 7 ppm of compound 103 to 6% by weight sucrose. Panelists were asked to evaluate the four samples and rate their sweetness on a scale of 0 to 10, with higher scores indicating stronger sweetness. Table 3 shows the average scores from the panelists.

[0214] [Table 3]

Claims

1. Flavoring compounds that are compounds of formula (I) or salts thereof: 【Chemistry 1】 [In the formula, R １ and R ２ These are, independently of each other, a hydrogen atom, -OH, or -OCH. ３ And, R ３ , R ４ , and R ５ These are, independently of each other, a hydrogen atom, -OH, or -OCH. ３ And, R is methyl, ethyl, isopropyl, or benzyl.

2. R １ and R ２ The flavor-modifying compound according to claim 1, wherein both are -OH.

3. R １ and R ２ The flavor-modifying compound according to claim 1, wherein one of the atoms is a hydrogen atom and the other is a hydrogen atom.

4. R ４ However, it is -OH, and R ３ and R ５ The flavor-adjusting compound according to any one of claims 1 to 3, wherein each of the atoms is a hydrogen atom.

5. R ３ However, it is -OH, and R ４ However, -OCH ３ And R ５ The flavor-modifying compound according to any one of claims 1 to 3, wherein the atom is a hydrogen atom.

6. A flavor-modifying compound according to any one of claims 1 to 5, wherein R is methyl or ethyl.

7. A flavor-modifying compound according to any one of claims 1 to 6, which is compound 101, compound 102, compound 103, compound 104, compound 105, compound 106, or any of the aforementioned ingestible salts.

8. Use of a flavor-modifying compound according to any one of claims 1 to 7 to reduce the bitterness of an ingestible composition.

9. The use according to claim 8, wherein the concentration of the flavor-adjusting compound used in the ingestible composition is in the range of 0.1 ppm to 1000 ppm.

10. The use according to claim 8 or 9, wherein the ingestible composition contains one or more bitter substances.

11. The bitter substances include 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 The use according to claim 10, which is a high-strength sweetener such as 11-oxomogloside V or a 1,6-α isomer of siamenoside I, or any combination thereof.

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

13. The use according to claim 10, wherein the bitter substance is a plant 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.

14. The use according to claim 10, wherein the bitter substance is a pharmaceutical compound such as atropine, brinzolamide, chloramphenicol, chloroquine, clindamycin, dexamethasone, digoxin, diltiazem, diphenhydramine, docusate, dorzolamide, doxepin, doxylamine, enalapril, erythromycin, esomeprazole, famotidine, gabapentin, gincolide A, guaifenesin, L-histidine, lomefloxacin, methylprednisolone, ofloxacin, oleuropein, oxyphenonium, pirenzepine, prednisone, ranitidine, trapidil, trimethoprim, cetirizine, or any combination thereof.

15. Use of a flavor-modifying compound according to any one of claims 1 to 7 for enhancing the sweetness of an ingestible composition.

16. The use according to claim 15, wherein the concentration of the flavor-adjusting compound used in the ingestible composition is in the range of 0.1 ppm to 1000 ppm.

17. The use according to claim 15 or 16, wherein the ingestible composition contains one or more bitter substances.

18. An ingestible composition comprising a flavor-modifying compound according to any one of claims 1 to 7 and a bulking agent.

19. An ingestible composition according to claim 18, comprising a sweetener.

20. The edible composition according to claim 18 or 19, wherein the flavor-adjusting compound is present in the edible composition at a concentration in the range of 0.1 ppm to 1000 ppm.

21. A flavored product comprising the ingestible composition according to any one of claims 18 to 20.

22. A flavored product according to claim 21, which is a beverage product, food product, oral care product, or pharmaceutical product.

Images