Flavanone derivatives, and use of flavanone derivatives as sweetness enhancers

Abstract

To provide flavanone derivatives and their use as sweetness enhancers.SOLUTION: There is provided use of a flavor-modifying compound to (a) enhance a sweet taste, (b) reduce a bitter taste, or (c) reduce a sour taste, of an ingestible composition, wherein the flavor-modifying compound is a compound of formula (I) or a salt thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 896,017, filed September 5, 2019, and European Patent Application Publication No. 19200701.1, filed October 1, 2019, the entire contents of both of which are incorporated herein by reference.

[0002] Technical Field The present disclosure generally provides flavanone derivatives and their use as sweetness enhancers. In some embodiments, the present disclosure provides compositions containing such flavanone derivatives, such as compositions containing such flavanone derivatives and one or more other sweeteners. In other embodiments, the present disclosure provides methods for reducing the calorie content of sweetened products, such as sweetened food or beverage products.

[0003] 2. Description of Related Art The gustatory system provides sensory information about the chemical composition of the external world. Gustatory transduction is one of the more sophisticated forms of chemically induced 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 modalities: sweet, bitter, sour, salty, and umami.

[0004] Sweetness is the most commonly perceived taste when consuming sugar-rich foods. Mammals generally perceive sweetness as a pleasant sensation, except when excessive. Caloric sweeteners, such as sucrose and fructose, are prototypical examples of sweet tastants. Although various non-caloric and low-calorie alternatives exist, these caloric sweeteners are the primary means by which food products induce the perception of sweetness upon consumption.

[0005] Metabolic disorders and related conditions, such as obesity, diabetes, and cardiovascular disease, are major public health concerns worldwide, and their prevalence is increasing at an alarming rate in nearly all developed countries. Caloric sweeteners are a major factor in this trend, as they are included in various packaged food and beverage products to make them more palatable to consumers. In many cases, non-caloric or low-calorie substitutes can be used in place of sucrose or fructose in foods and beverages. Even so, these compounds impart a sweetness different from that of caloric sweeteners, and many consumers do not consider them suitable substitutes. Furthermore, such compounds can be difficult to incorporate into certain products. While they may be used as partial substitutes for caloric sweeteners in some cases, their mere presence can cause many consumers to perceive unpleasant off-tastes, including astringency, bitterness, metallic taste, and licorice flavor. Therefore, low-calorie sweeteners face certain challenges to their adoption.

[0006] Sweetness enhancement offers an alternative approach to overcome some of the selection challenges faced by low-calorie sweeteners. Such compounds can be used in combination with sucrose or fructose to enhance their sweetness, thereby allowing for the use of smaller amounts of such calorie sweeteners in various food or beverage products. However, in addition to enhancing the perceived sweetness of primary sweeteners, such compounds also alter the perceived taste of the sweetener. Thus, many consumers find such sweetness-enhanced products more unpleasant to consume than non-enhanced alternatives with higher calories. Therefore, there remains a need to discover compounds that enhance the sweetness of calorie sweeteners without altering the perceived taste in a way that diminishes the pleasure consumers experience from eating or drinking products containing such sweeteners.

[0007] summary The present disclosure relates to the discovery that certain compounds exhibit desirable and surprising sweetness enhancing effects when combined with a primary sweetener in a sweetness enhancing effective amount.

[0008] In a first aspect, the present disclosure provides a flavor-modifying compound that is a compound of formula (I) or a salt thereof: [ka] [In the formula, R 1 is a hydrogen atom, -OH, or -OR 1A and R 1A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 1A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 2 is a hydrogen atom, -OH, or -OR 2A and R 2A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 2A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 3 is -OH or -OR 3A and R 3A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 3A is a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 4 is a hydrogen atom, -OH, or -OR 4A and R 4A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 4A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 5 -OH, -OR 5A , or -OC(O)-R 5B and R 5A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 5A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 5B -H, or -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 is alkyl, R 6 and R 7 independently, C 1-6 Alkyl, -OH, C 1-6 Alkoxy, and -O-(C 1-6 alkylene)-O-(C 1-6 alkyl), m is 0, 1, or 2, and n is 0, 1, 2, or 3].

[0009] In a second and related aspect, the present disclosure provides a compound of formula (Ia): [ka] or a salt thereof.

[0010] In a third and related aspect, the present disclosure provides a compound of formula (Ic): [ka] or a salt thereof.

[0011] In a fourth aspect, the present disclosure provides the use of a flavour modifying compound of any of the first to third aspects.

[0012] In a fifth aspect, the present disclosure provides use of a flavor-modifying compound of any of the first to third aspects to enhance the sweetness of an ingestible composition. In some embodiments thereof, the ingestible composition comprises a caloric sweetener. In some other embodiments thereof, the ingestible composition comprises a non-caloric sweetener. In some embodiments, the sweetener is a high-intensity sweetener.

[0013] In a sixth aspect, the present disclosure provides the use of a flavor modifying compound of any of the first to third aspects to reduce the sourness of an ingestible composition.

[0014] In a seventh aspect, the present disclosure provides the use of a flavor modifying compound of any of the first to third aspects to reduce the bitter taste of an ingestible composition.

[0015] In an eighth aspect, the present disclosure provides use of a flavor-modifying compound of any of the first to third aspects in the manufacture of an ingestible composition to enhance the sweetness of the ingestible composition. In some embodiments thereof, the ingestible composition comprises a caloric sweetener. In some other embodiments thereof, the ingestible composition comprises a non-caloric sweetener. In some embodiments, the sweetener is a high-intensity sweetener.

[0016] In a ninth aspect, the present disclosure provides the use of a flavor modifying compound of any of the first to third aspects in the manufacture of an ingestible composition to reduce the sourness of the ingestible composition.

[0017] In a tenth aspect, the present disclosure provides the use of a flavor modifying compound of any of the first to third aspects in the manufacture of an ingestible composition to reduce the bitterness of the ingestible composition.

[0018] In an eleventh aspect, the present disclosure provides a method of enhancing the sweetness of an ingestible composition, comprising introducing into the ingestible composition an amount (e.g., an amount having a sweetness enhancing effect) of a compound of any of the first through third aspects.

[0019] In a twelfth aspect, the present disclosure provides a method of reducing the sourness of an ingestible composition, comprising introducing into the ingestible composition an amount (e.g., an amount having a sourness-reducing effect) of a compound of any of the first through third aspects.

[0020] In a thirteenth aspect, the present disclosure provides a method of reducing the bitterness of an ingestible composition, comprising introducing into the ingestible composition an amount (e.g., a bitterness-reducing effective amount) of a compound of any of the first to third aspects.

[0021] In a fourteenth aspect, the present disclosure provides a composition comprising a compound of any of the first to third aspects, comprising at least 50% by weight of the composition by dry weight (e.g., by total weight of the composition excluding the weight of any liquid carrier).

[0022] In a fifteenth aspect, the present disclosure provides a solid composition comprising a compound of any of the first to third aspects, wherein the compound constitutes at least 50% by weight of the solid composition, based on the total weight of the composition.

[0023] In a sixteenth aspect, the present disclosure provides an ingestible composition comprising a compound of any of the first to third aspects, wherein the concentration of the compound of any of the first to third aspects in the ingestible composition is 200 ppm or less.

[0024] In a seventeenth aspect, the present disclosure provides an ingestible composition comprising a compound of any of the first through third aspects, comprising 1000 ppm or less of steviol glycosides, mogrosides, or functionalized derivatives thereof (including chemically or enzymatically functionalized derivatives). In some further embodiments, the ingestible composition comprises 1000 ppm or less of steviol glycosides.

[0025] In an eighteenth aspect, the present disclosure provides an ingestible composition comprising a compound of any of the first to third aspects, including a caloric sweetener, such as sucrose, fructose, glucose, xylitol, erythritol, or a combination thereof.

[0026] In a nineteenth aspect, the present disclosure provides a concentrated sweetening composition comprising a compound of any of the first to third aspects and a sweetener.

[0027] In a twentieth aspect, the present disclosure provides a flavored product comprising the composition of any of the preceding five aspects. In some embodiments, the flavored product is a beverage product, such as soda, flavored water, and tea. In some embodiments, the flavored product is a food product, such as yogurt.

[0028] In a twenty-first aspect, the present disclosure provides a method for producing a compound of the first to third aspects, comprising providing a flavanone that is not substituted at position 3, and contacting the flavanone with an enzyme to functionalize the flavanone at position 3. In some embodiments, further functionalization is performed.

[0029] Further aspects and embodiments thereof are described in the following detailed description, drawings, abstract, and claims.

[0030] The following drawings are provided for the purpose of illustrating various embodiments of the compositions and methods disclosed herein. The drawings are provided for illustrative purposes only and are not intended to illustrate preferred compositions or preferred methods or to serve as a source of any limitation on the scope of the claimed invention. [Brief explanation of the drawings]

[0031] [Figure 1]FIG. 1 shows chemical formulas illustrating non-limiting examples of compounds (or salts thereof) disclosed herein, wherein R1 and R2 are independently hydrogen, hydroxyl, optionally substituted alkoxy, glucuronate, or saccharidyloxy (e.g., a monosaccharide, disaccharide, trisaccharide, etc., comprising a furanose or pyranose moiety and linked to a flavanone core structure by a glycosidic bond); R3 is hydroxyl, optionally substituted alkoxy, glucuronate, or saccharidyloxy (e.g., as described above for R1 and R2); R4 is hydrogen, hydroxyl, optionally substituted alkoxy, glucuronate, or saccharidyloxy (e.g., as described above for R1 and R2); R5 is hydroxyl, optionally substituted alkoxy, glucuronate, formyloxy, or optionally substituted alkanoyloxy; and R6 and R7 are optionally substituents as described above.

[0032] Detailed Description of the Invention The following detailed description describes various aspects and embodiments provided herein. The description should be read from the perspective of one skilled in the relevant art and, as such, may not necessarily include information that is known to such skilled artisans.

[0033] definition The following terms and phrases have the meanings indicated below unless otherwise defined herein. This disclosure may use other terms and phrases not expressly defined herein. Such other terms and phrases have the meaning they would have within the written context of this disclosure to one of ordinary skill in the art. In some cases, terms or phrases may be defined in the singular or plural. In such cases, unless specifically indicated to the contrary, it is understood that any term in the singular may include its plural counterpart, and vice versa.

[0034] As used herein, "solvate" refers to a compound formed by the interaction of one or more solvent molecules with one or more compounds described herein. In some embodiments, the solvate is an ingestibly acceptable solvate, such as a hydrate.

[0035] As used herein, "C a ~C b " or "C a-b (where "a" and "b" are integers) refers to the number of carbon atoms in a particular group; that is, the group can contain from "a" to "b" carbon atoms. Thus, for example, a "C1-C4 alkyl" group or a "C 1-4 "Alkyl" groups refer to all alkyl groups having 1 to 4 carbon atoms, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)-, and (CH3)3C-.

[0036] As used herein, "halogen" or "halo" refers to any one of the radiostable atoms of Group 17 of the Periodic Table of the Elements, such as fluorine, chlorine, bromine, or iodine. In some embodiments, "halogen" or "halo" refers to fluorine or chlorine.

[0037] As used herein, "alkyl" refers to a straight or branched hydrocarbon chain that is fully saturated (i.e., contains no double or triple bonds). In some embodiments, the alkyl group has 1 to 20 carbon atoms. (As used herein, numerical ranges such as "1 to 20" refer to each integer within the given range: for example, "1 to 20 carbon atoms" means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to 20 carbon atoms, although this definition also covers the occurrence of the term "alkyl" without a specified numerical range.) The alkyl group may be a medium-sized alkyl having 1 to 9 carbon atoms. The alkyl group may be a lower alkyl having 1 to 4 carbon atoms. The alkyl group may also be a "C1-4 alkyl" or similar designations. 1-4 "Alkyl" indicates that the alkyl chain has 1 to 4 carbon atoms, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, and the like. Unless indicated to the contrary, the term "alkyl" refers to a group that is not further substituted.

[0038] As used herein, "substituted alkyl" refers to an alkyl group substituted with one or more substituents independently selected from the following: C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C7 carbocyclyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 3-10 membered heterocyclyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy). substituted), aryl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), halo, cyano, hydroxy, C1-C6 alkoxy, aryloxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C 3-C7 carbocyclyloxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 3-10 membered heterocyclyl-oxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryloxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7-carbo cyclyl-C1-C6-alkoxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 3-10 membered heterocyclyl-C1-C6-alkoxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl(C1-C6)alkoxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy),5-10 membered heteroaryl(C1-C6)alkoxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), sulfhydryl (mercapto), halo(C1-C6)alkyl (e.g., -CF3), halo(C1-C6)alkoxy (e.g., -OCF3), C1-C6 alkylthio, arylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7 aryl, carbocyclylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 3-10 membered heterocyclyl-thio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl-thio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7-carbocyclyl -C1-C6-alkylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 3-10 membered heterocyclyl-C1-C6-alkylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl(C1-C6)alkylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), , 5-10 membered heteroaryl(C1-C6)alkylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), amino, nitro, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, acyl, cyano, isocyanate, thiocyanate, isothiocyanate, sulfinyl, sulfonyl, and oxo(=O).

[0039] As used herein, "alkoxy" means a moiety of the formula -OR, where R is an alkyl group as defined above, including, but not limited to, for example, methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy. 1-9 Alkoxy".

[0040] As used herein, "alkylthio" means a moiety of the formula -SR, where R is an alkyl group as defined above, including, but not limited to, for example, methyl mercapto, ethyl mercapto, n-propyl mercapto, 1-methylethyl mercapto (isopropyl mercapto), n-butyl mercapto, iso-butyl mercapto, sec-butyl mercapto, tert-butyl mercapto, and the like. 1-9 "Alkylthio".

[0041] As used herein, "alkenyl" refers to a straight or branched hydrocarbon chain containing one or more double bonds. In some embodiments, an alkenyl group has 2 to 20 carbon atoms, although this definition also covers occurrences of the term "alkenyl" where no numerical range is specified. An alkenyl group may be a medium-sized alkenyl having 2 to 9 carbon atoms. An alkenyl group may be a lower alkenyl having 2 to 4 carbon atoms. An alkenyl group may also be referred to as a "C 2-4 Alkenyl" or similar names. 1-4"Alkenyl" indicates that the alkenyl chain has 2 to 4 carbon atoms, i.e., the alkenyl chain is selected from the group consisting of ethenyl, propen-1-yl, propen-2-yl, propen-3-yl, buten-1-yl, buten-2-yl, buten-3-yl, buten-4-yl, 1-methyl-propen-1-yl, 2-methyl-propen-1-yl, 1-ethyl-ethen-1-yl, 2-methyl-propen-3-yl, buta-1,3-dienyl, buta-1,2-dienyl, and buta-1,2-dien-4-yl. Typical alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl, and the like. Unless otherwise indicated, the term "alkenyl" refers to a group that is not further substituted.

[0042] As used herein, "alkynyl" refers to a straight or branched hydrocarbon chain containing one or more triple bonds. In some embodiments, an alkynyl group has 2 to 20 carbon atoms, although this definition also covers occurrences of the term "alkynyl" where no numerical range is specified. An alkynyl group may be a medium alkynyl having 2 to 9 carbon atoms. An alkynyl group may be a lower alkynyl having 2 to 4 carbon atoms. An alkynyl group may also be referred to as a "C 2-4 alkynyl" or similar names. 2-4 "Alkynyl" indicates that the alkynyl chain has 2 to 4 carbon atoms, i.e., the alkynyl chain is selected from the group consisting of ethynyl, propyn-1-yl, propyn-2-yl, butyn-1-yl, butyn-3-yl, butyn-4-yl, and 2-butynyl. Typical alkynyl groups include, but are not limited to, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless indicated to the contrary, the term "alkynyl" refers to a group that is not further substituted.

[0043] As used herein, "heteroalkyl" refers to a straight or branched hydrocarbon chain containing one or more heteroatoms, i.e., elements other than carbon, including, but not limited to, nitrogen, oxygen, and sulfur, in the chain backbone. In some embodiments, heteroalkyl groups have 1 to 20 carbon atoms, although this definition also covers occurrences of the term "heteroalkyl" where no numerical range is specified. Heteroalkyl groups may be medium-sized heteroalkyl groups having 1 to 9 carbon atoms. Heteroalkyl groups may be lower heteroalkyl groups having 1 to 4 carbon atoms. Heteroalkyl groups may also be referred to as "C 1-4 Heteroalkyl groups may contain one or more heteroatoms. 1-4 "Heteroalkyl" refers to a heteroalkyl group having 1 to 4 carbon atoms in the chain and one or more heteroatoms in the backbone of the chain. Unless otherwise specified, the term "heteroalkyl" refers to a group that is not further substituted.

[0044] As used herein, "alkylene" refers to a branched or straight-chain fully saturated diradical chemical group containing only carbon and hydrogen attached to the rest of the molecule through two points of attachment (i.e., alkanediyl). In some embodiments, alkylene groups have 1 to 20 carbon atoms, although this definition also covers occurrences of the term "alkylene" where no numerical range is specified. Alkylene groups may be medium-sized alkylenes having 1 to 9 carbon atoms. Alkylene groups may be lower alkylenes having 1 to 4 carbon atoms. An alkylene group may also be referred to as a "C 1-4 alkylene" or similar names. 1-4"Alkylene" indicates that the alkylene chain has 1 to 4 carbon atoms, i.e., the alkylene chain is selected from the group consisting of methylene, ethylene, ethane-1,1-diyl, propylene, propane-1,1-diyl, propane-2,2-diyl, 1-methyl-ethylene, butylene, butane-1,1-diyl, butane-2,2-diyl, 2-methyl-propane-1,1-diyl, 1-methyl-propylene, 2-methyl-propylene, 1,1-dimethyl-ethylene, 1,2-dimethyl-ethylene, and 1-ethyl-ethylene. Unless indicated to the contrary, the term "alkylene" refers to a group that is not further substituted.

[0045] As used herein, "alkenylene" refers to a straight or branched chain diradical chemical group containing only carbon and hydrogen and containing at least one carbon-carbon double bond attached to the rest of the molecule through two points of attachment. In some embodiments, an alkenylene group has 2 to 20 carbon atoms, although this definition also covers occurrences of the term "alkenylene" where no numerical range is specified. An alkenylene group may be a medium-sized alkenylene having 1 to 9 carbon atoms. An alkenylene group may be a lower alkenylene having 1 to 4 carbon atoms. An alkenylene group may also be referred to as a "C 2-4 Alkenylene" or similar names. 2-4"Alkenylene" indicates that the alkenylene chain has 2 to 4 carbon atoms, i.e., the alkenylene chain is selected from the group consisting of ethenylene, ethene-1,1-diyl, propenylene, propen-1,1-diyl, prop-2-ene-1,1-diyl, 1-methyl-ethenylene, but-1-enylene, but-2-enylene, but-1,3-dienylene, butene-1,1-diyl, but-1,3-dien-1,1-diyl, but-2-ene-1 ,1-diyl, but-3-ene-1,1-diyl, 1-methyl-prop-2-ene-1,1-diyl, 2-methyl-prop-2-ene-1,1-diyl, 1-ethyl-ethenylene, 1,2-dimethyl-ethenylene, 1-methyl-propenylene, 2-methyl-propenylene, 3-methyl-propenylene, 2-methyl-propen-1,1-diyl, and 2,2-dimethyl-ethen-1,1-diyl. Unless indicated to the contrary, the term "alkenylene" refers to a group that is not further substituted.

[0046] As used herein, "aromatic" means a ring or ring system having a conjugated pi-electron system and includes both carbocyclic aromatic (e.g., phenyl) and heterocyclic aromatic (e.g., pyridine) groups. The term includes monocyclic or fused-ring polycyclic groups (i.e., rings that share adjacent pairs of atoms), provided that the entire ring system is aromatic.

[0047] As used herein, "aryl" refers to an aromatic ring or ring system (i.e., two or more fused rings that share two adjacent carbon atoms) that contains only carbon in the ring backbone. When aryl is a ring system, all rings in the system are aromatic. In some embodiments, aryl groups have 6 to 18 carbon atoms, although this definition also covers occurrences of the term "aryl" where no numerical range is specified. In some embodiments, aryl groups have 6 to 10 carbon atoms. An aryl group is also referred to as "C 6-10 Aryl, C6-C 10Examples of aryl groups include, but are not limited to, phenyl, naphthyl, azulenyl, and anthracenyl. In some embodiments, the term "aryl" refers to phenyl. Unless otherwise indicated, the term "aryl" refers to a group that is not further substituted.

[0048] As used herein, "aryloxy" and "arylthio" refer to moieties of the formula RO- and RS-, respectively, where R is an aryl group as defined above, e.g., "C 6-10 aryloxy" or "C 6-10 and "arylthio", including but not limited to phenyloxy and phenylthio.

[0049] As used herein, "aralkyl" or "arylalkyl" refers to an aryl group linked, as a substituent, through an alkylene group, e.g., "C 7-14 In some embodiments, alkylene groups are lower alkylene groups (i.e., C 1-4 alkylene group).

[0050] As used herein, "heteroaryl" refers to an aromatic ring or ring system (i.e., two or more fused rings that share two adjacent atoms) that contains one or more heteroatoms, i.e., elements other than carbon, including, but not limited to, nitrogen, oxygen, and sulfur, in the ring backbone. When heteroaryl is a ring system, all rings in the system are aromatic. In some embodiments, heteroaryl groups have 5 to 18 ring members (i.e., the number of atoms that make up the ring backbone, including carbon atoms and heteroatoms), although this definition also covers occurrences of the term "heteroaryl" where no numerical range is specified. In some embodiments, heteroaryl groups have 5 to 10 ring members or 5 to 7 ring members. Heteroaryl groups may be referred to as "5-7-membered heteroaryl," "5-10-membered heteroaryl," or similar designations. Examples of heteroaryl rings include, but are not limited to, furyl, thienyl, phthalazinyl, pyrrolyl, oxazolyl, thiazole, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, triazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquininyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, indolyl, isoindolyl, and benzothienyl. Unless indicated to the contrary, the term "heteroaryl" refers to a group that is not further substituted.

[0051] As used herein, "heteroaralkyl" or "heteroarylalkyl" refers to a heteroaryl group linked, as a substituent, via an alkylene group. Examples include, but are not limited to, 2-thienylmethyl, 3-thienylmethyl, furylmethyl, thienylethyl, pyrrolylalkyl, pyridylalkyl, isoxazolylalkyl, and imidazolylalkyl. In some cases, the alkylene group may be a lower alkylene group (i.e., C 1-4 alkylene group).

[0052] As used herein, "carbocyclyl" refers to a non-aromatic cyclic ring or ring system containing only carbon atoms in the ring system backbone. When a carbocyclyl is a ring system, two or more rings may be joined together in a fused, bridged, or spiro-linked manner. A carbocyclyl may have any degree of saturation, as long as at least one ring in the ring system is not aromatic. Thus, carbocyclyl includes cycloalkyl, cycloalkenyl, and cycloalkynyl. In some embodiments, a carbocyclyl group has 3 to 20 carbon atoms, although this definition also covers occurrences of the term "carbocyclyl" where no numerical range is specified. A carbocyclyl group may be a medium-sized carbocyclyl having 3 to 10 carbon atoms. A carbocyclyl group may be a carbocyclyl having 3 to 6 carbon atoms. A carbocyclyl group may also be referred to as a "C 3-6 It may be represented as "carbocyclyl" or similar names. Examples of carbocyclyl rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, 2,3-dihydro-indene, bicycle[2.2.2]octanyl, adamantyl, and spiro[4.4]nonanyl. Unless indicated to the contrary, the term "carbocyclyl" refers to a group that is not further substituted.

[0053] As used herein, "(carbocyclyl)alkyl" means, as a substituent, a carbocyclyl group linked via an alkylene group, e.g., "C 4-10 (carbocyclyl)alkyl" and the like, including, but not limited to, cyclopropylmethyl, cyclobutylmethyl, cyclopropylethyl, cyclopropylbutyl, cyclobutylethyl, cyclopropylisopropyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, cycloheptylmethyl, and the like. In some cases, the alkylene group is a lower alkylene group.

[0054] As used herein, "cycloalkyl" means a fully saturated carbocyclyl ring or ring system according to any of the embodiments set forth above for carbocyclyl. Examples include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0055] As used herein, "cycloalkenyl" means a carbocyclyl ring or ring system in which the ring in the ring system is not aromatic and has at least one double bond, according to any of the embodiments described above for carbocyclyl. An example is cyclohexenyl.

[0056] As used herein, "heterocyclyl" refers to a non-aromatic cyclic ring or ring system containing only carbon atoms in the ring system backbone. Heterocyclyls may be joined together in fused, bridged, or spiro-linked ways. Heterocyclyls may have any degree of saturation, so long as at least one ring in the ring system is aromatic. Heteroatoms may be present in either the non-aromatic or aromatic ring in the ring system. In some embodiments, heterocyclyl groups have 3 to 20 ring members (i.e., the number of atoms comprising the ring backbone, including carbon atoms and heteroatoms), although this definition also covers occurrences of the term "heterocyclyl" where no numerical range is specified. Heterocyclyl groups may be medium-sized heterocyclyls having 3 to 10 ring members. Heterocyclyl groups may be heterocyclyls having 3 to 6 ring members. Heterocyclyl groups may be referred to as "3- to 6-membered heterocyclyl" or similar names. In preferred 6-membered monocyclic heterocyclyls, the heteroatoms are selected from one to three of O, N or S, and in preferred 5-membered monocyclic heterocyclyls, the heteroatoms are selected from one or two heteroatoms selected from O, N or S.Examples of heterocyclyl rings are azepinyl, acridinyl, carbazolyl, cinnolinyl, dioxolanyl, imidazolinyl, imidazolidinyl, morpholinyl, oxiranyl, oxepanyl, thiepanyl, piperidinyl, piperazinyl, dioxopiperazinyl, pyrrolidinyl, pyrrolidionyl, pyrrolidionyl, 4-piperidonyl, pyrazolinyl, pyrazolidinyl, 1,3-dioxinyl, 1,3-dioxanyl, 1,4-dioxinyl, 1,4-dioxanyl, 1,3-oxathianyl, 1,4-oxathiinyl, 1,4-oxathianyl, 2H-1,2-oxazinyl, trioxanyl, hexahydro- These include, but are not limited to, 1,3,5-triazinyl, 1,3-dioxolyl, 1,3-dioxolanyl, 1,3-dithiolyl, 1,3-dithiolanyl, isoxazolinyl, isoxazolidinyl, oxazolinyl, oxazolidinyl, oxazolidinonyl, thiazolinyl, thiazolidinyl, 1,3-oxathiolanyl, indolinyl, isoindolinyl, tetrahydrofuran, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydro-1,4-thiazinyl, thiamorpholinyl, dihydrobenzofuranyl, benzimidazolidinyl, and tetrahydroquinoline.

[0057] As used herein, "(heterocyclyl)alkyl" refers to a heterocyclyl group linked, as a substituent, via an alkylene group. Examples include, but are not limited to, imidazolinylmethyl and indolinylethyl.

[0058] An "acyl" group refers to a -C(=O)R group, where R is hydrogen, C, as defined herein. 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl. Non-limiting examples include formyl, acetyl, propanoyl, benzoyl, and acryl.

[0059] An "O-carboxy" group refers to an "-OC(=O)R" group, where R is hydrogen, C, as defined herein. 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0060] A "C-carboxy" group refers to a "-C(=O)OR" group, where R is hydrogen, C, as defined herein. 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5-10 membered heteroaryl, and 3-10 membered heterocycyl. A non-limiting example includes carboxyl (i.e., -C(=O)OH).

[0061] A "cyano" group refers to a "-CN" group.

[0062] A "cyanate" group refers to a "-OCN" group.

[0063] An "isocyanate" group refers to an "-NCO" group.

[0064] A "thiocyanate" group refers to a "-SCN" group.

[0065] An "isothiocyanate" group refers to a "-NCS" group.

[0066] A "sulfinyl" group refers to a "-S(=O)R" group, where R is hydrogen, C, as defined herein. 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0067] A "sulfonyl" group refers to a "-SO2R" group, where R is hydrogen, C, as defined herein. 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0068] The "S-sulfonamide" group is "-SONR A R B " group, where R A and R B are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0069] An "N-sulfonamido" group is defined as "-N(R A )SO2R B " group, where R A and R b are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0070] The "O-carbamyl" group is "-OC(=O)NR A R B " group, where R A and R B are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0071] The "N-carbamyl" group is defined as "-N(R A )C(=O)OR B " group, where R A and R B are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0072] The "O-thiocarbamyl" group is "-OC(=S)NR A R B " group, where R A and R B are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0073] The "N-thiocarbamyl" group is defined as "-N(R A )C(=S)OR B " group, where R A and R B are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0074] A "C-amido" group is defined as "-C(=O)NR A R B " group, where R A and R B are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0075] An "N-amido" group is defined as "-N(R A )C(=O)R B " group, where R A and R B are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycyl.

[0076] The "amino" group is "-NR A R B " group, where R A and R B are each independently, as defined herein, hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclyl, C 6-10 It is selected from aryl, 5-10 membered heteroaryl, and 3-10 membered heterocycyl. Non-limiting examples include free amino (i.e., -NH2).

[0077] An "aminoalkyl" group refers to an amino group linked via an alkylene group.

[0078] An "alkoxyalkyl" group is an alkoxy group attached via an alkylene group, e.g., "C 2-8 "Alkoxyalkyl" and the like.

[0079] As used herein, a "glucosyl moiety" is a monovalent moiety in which one of the hydroxyl groups of glucose is replaced by a bond to another atom, functional group, or moiety. Unless otherwise specified, glucose can have any suitable stereochemistry. Thus, the term includes moieties having D-stereochemistry and moieties having L-stereochemistry. Furthermore, the term includes moieties having α-stereochemistry and moieties having β-stereochemistry. The carbon atoms of the glucosyl moiety follow conventional numbering, as shown below. This diagram is shown for β-D glucose, but applies in an analogous manner to glucosyl moieties having α and / or L-stereochemistry: [ka]

[0080] As used herein, a "glucuronyl moiety" is a monovalent moiety in which one of the hydroxyl groups of glucuronic acid is replaced by a bond to another atom, functional group, or moiety. Unless otherwise specified, glucuronic acid can have any suitable stereochemistry. Thus, the term includes moieties having D stereochemistry and moieties having L stereochemistry. Furthermore, the term includes moieties having α stereochemistry and moieties having β stereochemistry. The carbon atoms of the gluconyl moiety follow conventional numbering, as shown below. This diagram is shown for β-D gluconic acid, but applies in an analogous manner to glucuronyl moieties having α and / or L stereochemistry: [ka]

[0081] "C 1-6 The term "alkyl glucuronyl ester moiety" refers to the carboxylic acid group of glucuronic acid, which has a C substituted for a hydrogen atom of the carboxylic acid group.1-6 In any of the following embodiments, C refers to a glucuronyl moiety bearing an alkyl group (as defined in this paragraph). 1-6 The alkyl moiety may have any suitable value, for example, methyl, ethyl, isopropyl, propyl, butyl, pentyl, etc. In some embodiments, C 1-6 The alkyl moiety is methyl. 1-6 The alkyl moiety is ethyl.

[0082] As used herein, a substituent is derived from an unsubstituted parent group in which one or more hydrogen atoms have been replaced by another atom or group. Unless otherwise specified, when a group is considered to be "substituted," it means that the group is substituted with one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C7 carbocyclyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7-carbocyclyl-C1-C6-alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 3- to 10-membered ring. Heterosicyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 3-10 membered heterosicyl-C1-C6-alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl(C1-C6)alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl (halo, C1- C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl(C1-C6)alkyl (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), halo, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkoxy(C1-C6)alkyl (i.e., ether), aryloxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7 carbocyclyloxy (halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl,and C1-C6 haloalkoxy), 3-10 membered heterocyclyl-oxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryloxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7-carbocyclyl-C1-C6-alkoxy (halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 halo alkyl, and C1-C6 haloalkoxy), 3-10 membered heterocyclyl-C1-C6-alkoxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl(C1-C6)alkoxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl(C1-C6)alkoxy (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), and C3-C7 carbocyclylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), sulfhydryl (mercapto), halo(C1-C6)alkyl (e.g., -CF3), halo(C1-C6)alkoxy (e.g., -OCF3), C1-C6 alkylthio, arylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7 carbocyclylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), and -C6 haloalkoxy), 3-10 membered heterocyclyl-thio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl-thio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), C3-C7-carbocyclyl-C1-C6-alkylthio (halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl,and C1-C6 haloalkoxy), 3-10 membered heterocyclyl-C1-C6-alkylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), aryl(C1-C6)alkylthio (optionally substituted with halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), 5-10 membered heteroaryl(C1-C6)alkylthio(halo , C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy), amino, amino(C1-C6)alkyl, nitro, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, acyl, cyanate, isocyanate, thiocyanate, isothiocyanate, sulfinyl, sulfonyl, and oxo (=O). When a group is described as being "optionally substituted," the group can be substituted with said substituents.

[0083] It should be understood that certain radical naming conventions can include either monoradicals or diradicals, depending on the context. For example, if the substituent requires two points of attachment to the rest of the molecule, the substituent is understood to be a diradical. For example, a substituent identified as alkyl, which requires two points of attachment, includes diradicals such as -CH2-, -CH2CH2-, -CH2CH(CH3)CH2-. Other radical naming conventions explicitly indicate that the radical is a diradical, such as an "alkylene" or "alkenylene."

[0084] Where a substituent is depicted as a diradical (i.e., having two points of attachment to the rest of the molecule), it is to be understood that the substituent may be attached in any orientation unless otherwise stated. Thus, for example, -AE- or [ka] Substituents depicted as include those oriented such that A is attached to the point of attachment at the left end of the molecule and A is attached to the point of attachment at the right end of the molecule.

[0085] As used herein, the terms "sweetener," "sweet flavoring agent," "sweet flavor entity," or "sweet compound" refer to a compound or an ingestible acceptable salt thereof that induces a detectable sweet taste in a subject, e.g., a compound that activates the T1R2 / T1R3 receptor in vitro.

[0086] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, reference to a "substituent" includes a single substituent as well as two or more substituents, etc.

[0087] As used herein, "for example," "for instance," "such as," or "including" is meant to introduce examples that further clarify a more general subject matter. Unless otherwise specified, such examples are provided merely as an aid in understanding the embodiments set forth in this disclosure and are not meant to be limiting in any way. Nor do these terms imply any preference of any kind for the disclosed embodiments.

[0088] As used herein, "comprise" or "comprises" or "comprising" or "comprised of" refers to an open group, meaning that the group can include additional components in addition to those explicitly listed. For example, the phrase "comprising A" means that A must be present, but other components can also be present. The terms "include," "have," and "composed of," and their grammatical variations, have the same meaning. In contrast, "consist of" or "consists of" or "consisting of" refers to a closed group. For example, the phrase "consisting of A" means that A and only A are present.

[0089] As used herein, "optionally" means that the subsequently described event may or may not occur. In some embodiments, the optional event does not occur. In other embodiments, the optional event occurs one or more times.

[0090] As used herein, "or" should be given its broadest reasonable interpretation and should not be limited to an either / or construction. Thus, the phrase "comprising A or B" means that A is present and B is not present, or B is present and A is not present, or both A and B are present. Furthermore, for example, if A defines a class that can have multiple members, e.g., A1 and A2, one or more members of the class can be present at the same time.

[0091] As used herein, the term "flavor modifying compound" refers to a compound of Formula (I) or a salt thereof, or any embodiment thereof described herein. For example, in some cases, the term "flavor modifying compound" refers to a compound of Formula (Ia). In some cases, the term "flavor modifying compound" refers to a compound of Formula (Ib). In some cases, the term "flavor modifying compound" refers to a compound of Formula (Ic). In some cases, the term "flavor modifying compound" refers to a compound of Formula (Id).

[0092] As used herein, certain substituents or linking groups having only a single atom may be referred to by the name of the atom. For example, in some cases, the substituent "-H" may be referred to as "hydrogen" or "hydrogen atom," the substituent "-F" may be referred to as "fluorine" or "fluorine atom," and the linking group "-O-" may be referred to as "oxygen" or "oxygen atom."

[0093] The point of attachment of a group is usually indicated by a dash (-) or an asterisk (*). For example, groups such as *-CH2-CH3 or -CH2-CH3 both represent an ethyl group.

[0094] Chemical structures are often shown using a "skeletal" format so that carbon atoms are not explicitly shown, and hydrogen atoms attached to carbon atoms are omitted entirely. For example, the structure [ka] represents butane (i.e., n-butane). Additionally, aromatic groups, such as benzene, are represented by showing one of the contributing resonance structures. For example, the structure [ka] represents toluene.

[0095] Positions on the flavanone ring may be referred to by numbers such as "position 2," "position 3," etc. These terms refer to specific positions on the fused ring structure of the flavanone, even if further substitution of the fused ring structure may occur at different numbered positions. Thus, for example, a carbonyl-substituted position may, in some embodiments, be said to occur at the "4-position," regardless of whether addition of a further substituent would result in a position other than the 4-position on the fused ring structure. Similarly, a substituted phenyl substituent position on the fused ring structure may, in some embodiments, be said to occur at the "2-position," regardless of whether addition of a further substituent would result in a position other than the 2-position on the fused ring structure.

[0096] Other terms not included in this subsection are defined elsewhere in this description.

[0097] Flavanone derivatives In a first aspect, the present disclosure provides a flavor modifying compound that is a compound of formula (I) or a salt thereof: [ka] [In the formula, R 1 is a hydrogen atom, -OH, or -OR 1A and R 1A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 1A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 2 is a hydrogen atom, -OH, or -OR 2A and R 2A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6alkyl or R 2A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 3 is -OH or -OR 3A and R 3A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 3A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 4 is a hydrogen atom, -OH, or -OR 4A and R 4A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 4A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 5 -OH, -OR 5A , or -OC(O)-R 5B and R 5A -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 5A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose moieties and pyranose moieties; R 5B -H, or -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 is alkyl, R 6 and R 7 independently, C 1-6 Alkyl, -OH, C 1-6 Alkoxy, and -O-(C 1-6 alkylene)-O-(C 1-6 alkyl), m is 0, 1, or 2, and n is 0, 1, 2, or 3].

[0098] Various embodiments of the foregoing aspects are also considered part of this disclosure, and are described below and throughout other parts of the detailed description.

[0099] In some embodiments of the first aspect, R 1 is a hydrogen atom. In some other embodiments, R 1 is —OH. In some other embodiments, R 1 HA-OR 1A In some further such embodiments of any of the foregoing embodiments, R 1A is optionally substituted as described above 1-6 In some other embodiments, R 1A is the unsubstituted C 1-6 alkyl, such as methyl, ethyl, or isopropyl. In some embodiments, R 1A is methyl. In some other embodiments, R 1A is a glucuronyl moiety. In some other embodiments, R 1A is a furanose or pyranose moiety, e.g., a glucosidyl moiety. 1Ais an oligosaccharide moiety as defined above, such as a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety, or a pentaglucosidyl moiety.

[0100] In some embodiments of any of the foregoing embodiments, R 2 is a hydrogen atom. In some other embodiments, R 2 is —OH. In some other embodiments of any of the above embodiments, R 2 HA-OR 2A In some further such embodiments, R 2A is optionally substituted as described above 1-6 In some other embodiments, R 2A is the unsubstituted C 1-6 alkyl, such as methyl, ethyl, or isopropyl. In some embodiments, R 2A is methyl. In some other embodiments, R 2A is a glucuronyl moiety. In some other embodiments, R 2A is a furanose or pyranose moiety, e.g., a glucosidyl moiety. 2A is an oligosaccharide moiety as defined above, such as a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety, or a pentaglucosidyl moiety.

[0101] In some embodiments of any of the foregoing embodiments, R 3 is —OH. In some other embodiments of any of the above embodiments, R 3 HA-OR 3A In some further such embodiments, R 3A is optionally substituted as described above 1-6 In some other embodiments, R 3A is the unsubstituted C 1-6 alkyl, such as methyl, ethyl, or isopropyl. In some embodiments, R 3Ais methyl. In some other embodiments, R 3A is a glucuronyl moiety. In some other embodiments, R 3A is a furanose or pyranose moiety, e.g., a glucosidyl moiety. 3A is an oligosaccharide moiety as defined above, such as a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety, or a pentaglucosidyl moiety.

[0102] In some embodiments of any of the foregoing embodiments, R 4 is a hydrogen atom. In some other embodiments of any of the above embodiments, R 4 is —OH. In some other embodiments of any of the above embodiments, R 4 HA-OR 4A In some further such embodiments, R 4A is optionally substituted as described above 1-6 In some other embodiments, R 4A is the unsubstituted C 1-6 alkyl, such as methyl, ethyl, or isopropyl. In some embodiments, R 4A is methyl. In some other embodiments, R 4A is a glucuronyl moiety. In some other embodiments, R 4A is a furanose or pyranose moiety, e.g., a glucosidyl moiety. 4A is an oligosaccharide moiety as defined above, such as a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety, or a pentaglucosidyl moiety.

[0103] In some embodiments of any of the foregoing embodiments, R 5 is —OH. In some other embodiments of any of the above embodiments, R 5 HA-OR 5A In some further such embodiments, R 5Ais optionally substituted as described above 1-6 In some other embodiments, R 5A is the unsubstituted C 1-6 alkyl, such as methyl, ethyl, or isopropyl. In some embodiments, R 5A is methyl. In some other embodiments, R 5A is a glucuronyl moiety. In some other embodiments, R 5A is a furanose or pyranose moiety, e.g., a glucosidyl moiety. 5A is an oligosaccharide moiety as described above, e.g., a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety, or a pentaglucosidyl moiety. In some other embodiments of any of the foregoing embodiments, R 5 Ha-OC(O)-R 5B In some further such embodiments, R 5B is optionally substituted as described above 1-6 In some other embodiments, R 5B is the unsubstituted C 1-6 alkyl, such as methyl, ethyl, or isopropyl. In some embodiments, R 5B is methyl. In some other such embodiments, R 5B is a hydrogen atom.

[0104] The variables m and n can have any suitable values ​​within the above-mentioned limits. In some embodiments of any of the above embodiments, m is 0. In some other embodiments of any of the above embodiments, m is 1. In some embodiments of any of the above embodiments, n is 0. In some other embodiments of any of the above embodiments, n is 1. R 6Note that R denotes non-hydrogen substituents optionally present at two positions on the phenyl moiety of the bicyclic ring system, representing positions 6 and 8, according to conventional numbering for flavanones. Thus, when m is 0, both substituents at these positions are hydrogen atoms. When m is 1, R 6 There is a non-hydrogen substituent at one of two positions, selected from the variables given in the definition of R, and when m is 2, there are non-hydrogen substituents at both positions. In a similar manner, R 7 refers to non-hydrogen substituents optionally present at three positions on the phenyl ring attached to the 2-position of the bicyclic ring (according to conventional position numbering for flavanones). Thus, when n is 0, these three positions (i.e., R 3 and R 4 The substituents at n (and the three positions other than the position occupied by n) are hydrogen atoms; and when n is 1, there is a non-hydrogen substituent at one of these three available positions; when n is 2, there are non-hydrogen substituents at two of these three available positions; and when n is 3, there is a non-hydrogen substituent at each of these three available positions.

[0105] In some embodiments of any of the foregoing embodiments, R 1 and R 2 is -OH and R 3 is -OH or -OCH3, and R 4 is -H or -OH, and R 5 is -OC(O)-CH3, and R 6 and R 7 is -H.

[0106] In a related aspect, the present disclosure provides a compound of formula (Ia): [ka] or a salt thereof. In some embodiments thereof, the compound exists as a mixture of any two or more, any three or more, or all four stereoisomers encompassed by its structure, i.e., (2R,3R), (2R,3S), (2S,3R), and (2S,3S). In some further embodiments, the compound exists in substantially pure form of one of the four stereoisomers, i.e., at a purity of 95% or more, or 97% or more, or 98% or more, or 99% or more, or 99.5%, or 99.7% or more, or 99.9% or more.

[0107] In some further embodiments thereof, the flavor-modifying compound has formula (Ib): [ka] or a salt thereof.

[0108] In a related aspect, the present disclosure provides a compound of formula (Ic): [ka] or a salt thereof. In some embodiments thereof, the compound exists as a mixture of any two or more, any three or more, or all four stereoisomers encompassed by its structure, i.e., (2R,3R), (2R,3S), (2S,3R), and (2S,3S). In some further embodiments, the compound exists in substantially pure form of one of the four stereoisomers, i.e., at a purity of 95% or more, or 97% or more, or 98% or more, or 99% or more, or 99.5%, or 99.7% or more, or 99.9% or more.

[0109] In some further embodiments thereof, the flavor-modifying compound has the formula (Id): [ka] or a salt thereof.

[0110] When the compounds disclosed herein have at least one chiral center, they can exist as individual enantiomers and diastereomers, or as mixtures of such isomers. In some embodiments related to the second aspect, the sweetness enhancing compound has substantial enantiomeric purity.

[0111] For example, in some embodiments, the (2R,3R) enantiomer of a composition comprising a compound of Formula (Ia) or a salt thereof constitutes at least 50% by weight, or at least 60% by weight, or at least 70% by weight, or at least 80% by weight, or at least 90% by weight, or at least 95% by weight, or at least 97% by weight, or at least 99% by weight of the compound present in the composition, relative to the total amount of compounds in the composition [i.e., the amount of (2R,3R) + the amount of (2S,3R) + the amount of (2R,3S) + the amount of (2S,3S)]. In some other embodiments, the (2R,3S) enantiomer of a composition comprising a compound of Formula (Ia) or a salt thereof constitutes at least 50% by weight, or at least 60% by weight, or at least 70% by weight, or at least 80% by weight, or at least 90% by weight, or at least 95% by weight, or at least 97% by weight, or at least 99% by weight of the compound present in the composition, relative to the total amount of compounds in the composition. In some other embodiments, the (2S,3R) enantiomer of a composition comprising a compound of Formula (Ia) or a salt thereof constitutes at least 50% by weight, or at least 60% by weight, or at least 70% by weight, or at least 80% by weight, or at least 90% by weight, or at least 95% by weight, or at least 97% by weight, or at least 99% by weight of the compound present in the composition, relative to the total amount of compounds in the composition. In some other embodiments, the (2S,3S) enantiomer of a composition comprising a compound of Formula (Ia) or a salt thereof constitutes at least 50% by weight, or at least 60% by weight, or at least 70% by weight, or at least 80% by weight, or at least 90% by weight, or at least 95% by weight, or at least 97% by weight, or at least 99% by weight of the compound present in the composition, relative to the total amount of compounds in the composition.

[0112] In some other embodiments of any of the embodiments of the preceding paragraph, the composition comprising a compound of Formula (Ia) or a salt thereof, the (2R,3R) enantiomer constitutes 50% by weight or less, or 40% by weight or less, or 30% by weight or less, or 20% by weight or less, or 10% by weight or less, or 5% by weight or less, or 3% by weight or less, or 1% by weight or less of the compounds present in the composition, relative to the total amount of compounds in the composition. In some other embodiments of any of the embodiments of the preceding paragraph, the composition comprising a compound of Formula (Ia) or a salt thereof, the (2R,3S) enantiomer constitutes 50% by weight or less, or 40% by weight or less, or 30% by weight or less, or 20% by weight or less, or 10% by weight or less, or 5% by weight or less, or 3% by weight or less, or 1% by weight or less of the compounds present in the composition, relative to the total amount of compounds in the composition. In some other embodiments of any of the embodiments of the preceding paragraph, the composition comprising a compound of Formula (Ia) or a salt thereof, the (2S,3R) enantiomer constitutes 50% by weight or less, or 40% by weight or less, or 30% by weight or less, or 20% by weight or less, or 10% by weight or less, or 5% by weight or less, or 3% by weight or less, or 1% by weight or less of the compounds present in the composition, relative to the total amount of compounds in the composition. In some other embodiments of any of the embodiments of the preceding paragraph, the composition comprising a compound of Formula (Ia) or a salt thereof, the (2S,3S) enantiomer constitutes 50% by weight or less, or 40% by weight or less, or 30% by weight or less, or 20% by weight or less, or 10% by weight or less, or 5% by weight or less, or 3% by weight or less, or 1% by weight or less of the compounds present in the composition, relative to the total amount of compounds in the composition.

[0113] For example, in some embodiments, the (2R,3R) enantiomer of a composition comprising a compound of Formula (Ic) or a salt thereof constitutes at least 50% by weight, or at least 60% by weight, or at least 70% by weight, or at least 80% by weight, or at least 90% by weight, or at least 95% by weight, or at least 97% by weight, or at least 99% by weight of the compound present in the composition, relative to the total amount of compounds in the composition [i.e., the amount of (2R,3R) + the amount of (2S,3R) + the amount of (2R,3S) + the amount of (2S,3S)]. In some other embodiments, the (2R,3S) enantiomer of a composition comprising a compound of Formula (Ic) or a salt thereof constitutes at least 50% by weight, or at least 60% by weight, or at least 70% by weight, or at least 80% by weight, or at least 90% by weight, or at least 95% by weight, or at least 97% by weight, or at least 99% by weight of the compound present in the composition, relative to the total amount of compounds in the composition. In some other embodiments, the (2S,3R) enantiomer of a composition comprising a compound of Formula (Ic) or a salt thereof constitutes at least 50% by weight, or at least 60% by weight, or at least 70% by weight, or at least 80% by weight, or at least 90% by weight, or at least 95% by weight, or at least 97% by weight, or at least 99% by weight of the compound present in the composition, relative to the total amount of compounds in the composition. In some other embodiments, the (2A,3S) enantiomer of a composition comprising a compound of Formula (Ic) or a salt thereof constitutes at least 50% by weight, or at least 60% by weight, or at least 70% by weight, or at least 80% by weight, or at least 90% by weight, or at least 95% by weight, or at least 97% by weight, or at least 99% by weight of the compound present in the composition, relative to the total amount of compounds in the composition.

[0114] In some other embodiments of any of the embodiments of the preceding paragraph, the composition comprises a compound of Formula (Ic) or a salt thereof, wherein the (2R,3R) enantiomer constitutes 50% by weight or less, or 40% by weight or less, or 30% by weight or less, or 20% by weight or less, or 10% by weight or less, or 5% by weight or less, or 3% by weight or less, or 1% by weight or less of the compounds present in the composition, relative to the total amount of compounds in the composition. In some other embodiments of any of the embodiments of the preceding paragraph, the composition comprises a compound of Formula (Ic) or a salt thereof, wherein the (2R,3S) enantiomer constitutes 50% by weight or less, or 40% by weight or less, or 30% by weight or less, or 20% by weight or less, or 10% by weight or less, or 5% by weight or less, or 3% by weight or less, or 1% by weight or less of the compounds present in the composition, relative to the total amount of compounds in the composition. In some other embodiments of any of the embodiments of the preceding paragraph, the composition comprising a compound of Formula (Ic) or a salt thereof, the (2S,3R) enantiomer constitutes 50% by weight or less, or 40% by weight or less, or 30% by weight or less, or 20% by weight or less, or 10% by weight or less, or 5% by weight or less, or 3% by weight or less, or 1% by weight or less of the compounds present in the composition, relative to the total amount of compounds in the composition. In some other embodiments of any of the embodiments of the preceding paragraph, the composition comprising a compound of Formula (Ic) or a salt thereof, the (2S,3S) enantiomer constitutes 50% by weight or less, or 40% by weight or less, or 30% by weight or less, or 20% by weight or less, or 10% by weight or less, or 5% by weight or less, or 3% by weight or less, or 1% by weight or less of the compounds present in the composition, relative to the total amount of compounds in the composition.

[0115] Separation of individual isomers or selective synthesis of individual isomers can be achieved by applying various methods well known to those skilled in the art. Unless otherwise specified (e.g., when the stereochemistry of a chiral center is explicitly indicated), all such isomers and mixtures thereof are included within the scope of the compounds disclosed herein. Furthermore, the compounds disclosed herein may exist in one or more crystalline or amorphous forms. Unless otherwise specified, all such forms are included within the scope of the compounds disclosed herein, including any polymorphic forms. Furthermore, some compounds disclosed herein may form solvates with water (i.e., hydrates) or common organic solvents. Unless otherwise specified, such solvates are included within the scope of the compounds disclosed herein.

[0116] Those skilled in the art will recognize that some structures depicted herein may be resonance forms or tautomers of compounds that can be fairly represented, even kinetically, by other chemical structures; those skilled in the art will recognize that such structures may represent only a small sample of such compounds. Such compounds are considered to be within the scope of the depicted structures, but such resonance forms or tautomers are not depicted herein.

[0117] Isotopes may be present in the described compounds. Each chemical element depicted in a compound structure may include any isotope of that element. For example, in a compound structure, a hydrogen atom may be explicitly disclosed or understood to be present in the compound. At any position in the compound where a hydrogen atom may be present, the hydrogen atom may be any isotope of hydrogen, including, but not limited to, hydrogen-1 (protium) and hydrogen-2 (deuterium). Thus, reference to a compound herein encompasses all possible isotopic forms unless the disclosure clearly indicates otherwise.

[0118] In some embodiments, the compounds disclosed herein are capable of forming acid and / or base salts by virtue of the presence of amino and / or carboxyl groups or groups similar thereto. Physiologically acceptable acid addition salts may be formed with inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Physiologically acceptable salts may be formed using inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, bases containing sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, etc., with ammonium, potassium, sodium, calcium, and magnesium salts being particularly preferred. In some embodiments, treatment of a compound disclosed herein with an inorganic base results in the loss of a labile hydrogen from the compound to form an inorganic cation, such as Li + , Na + , K. + , Mg 2+ and Ca 2+ Organic bases from which salts can be derived include, for example, primary amines, secondary amines, tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.

[0119] Use and Method In other aspects, the present disclosure provides the use of any of the flavor modifier compounds of the above aspects, including any embodiment or combination of embodiments described above. In certain related aspects, the present disclosure provides the use of any of the flavor modifier compounds of the above aspects, including any embodiment or combination of embodiments described above, to enhance the sweetness of an ingestible composition. In some embodiments thereof, the ingestible composition comprises a sweetener, e.g., a caloric sweetener. In certain other related aspects, the present disclosure provides the use of any of the flavor modifier compounds of the above aspects, including any embodiment or combination of embodiments described above, to reduce the sourness of an ingestible composition. In other related aspects, the present disclosure provides the use of any of the flavor modifier compounds of the above aspects, including any embodiment or combination of embodiments described above, to reduce the bitterness of an ingestible composition. In certain other related aspects, the present disclosure provides the use of any of the flavor modifier compounds of the above aspects, including any embodiment or combination of embodiments described above, in the manufacture of an ingestible composition to enhance the sweetness of the ingestible composition. In some embodiments thereof, the ingestible composition comprises a caloric sweetener. In another related aspect, the present disclosure provides the use of any of the flavor modifying compounds of the previous aspect, including any of the embodiments or combinations thereof described above, in the manufacture of an ingestible composition for reducing the sourness of the ingestible composition. In another related aspect, the present disclosure provides the use of any of the flavor modifying compounds of the previous aspect, including any of the embodiments or combinations thereof described above, in the manufacture of an ingestible composition for reducing the bitterness of the ingestible composition.

[0120] The present disclosure also provides methods corresponding to each of the above uses. Thus, in certain related aspects, the present disclosure provides methods for enhancing the sweetness of an ingestible composition, comprising incorporating into the ingestible composition an amount (e.g., a sweetness-enhancing amount) of a flavor-modifying compound of any of the above aspects, including any embodiment described above or combinations of those embodiments. In some other related aspects, the present disclosure provides methods for reducing the sourness of an ingestible composition, comprising incorporating into the ingestible composition an amount (e.g., a sourness-reducing amount) of a flavor-modifying compound of any of the above aspects, including any embodiment described above or combinations of those embodiments. In some other related aspects, the present disclosure provides methods for reducing the bitterness of an ingestible composition, comprising incorporating into the ingestible composition an amount (e.g., a bitterness-reducing amount) of a flavor-modifying compound of any of the above aspects, including any embodiment described above or combinations of those embodiments.

[0121] The uses and methods generally involve the use of a flavor modifying compound in a composition that includes one or more additional ingredients. For example, in at least one aspect, the present disclosure provides a composition comprising any of the flavor modifying compounds of the above aspects, including any embodiment or combination of embodiments described above, wherein the flavor modifying compound constitutes at least 50% of the composition by dry weight (e.g., by total weight of the composition excluding the weight of any liquid carrier). In a related aspect, the present disclosure provides a solid composition comprising any of the flavor modifying compounds of the above aspects, including any embodiment or combination of embodiments described above, wherein the flavor modifying compound constitutes at least 50% of the solid composition by total weight of the composition. In another related aspect, the present disclosure provides an ingestible composition comprising any of the flavor modifying compounds of the above aspects, including any embodiment or combination of embodiments described above, wherein the concentration of the flavor modifying compound in the ingestible composition is 200 ppm or less. In other related aspects, the disclosure provides ingestible compositions comprising any of the flavor-modifying compounds of the foregoing aspects, including any embodiment or combination of embodiments described above, wherein the ingestible composition comprises no more than 1000 ppm, or no more than 900 ppm, or no more than 800 ppm, or no more than 700 ppm, or no more than 600 ppm, or no more than 500 ppm, or no more than 400 ppm, or no more than 300 ppm, or no more than 200 ppm, or no more than 100 ppm, or no more than 50 ppm of steviol glycosides (including rebaudioside A). In other related aspects, the disclosure provides ingestible compositions comprising any of the flavor-modifying compounds of the foregoing aspects, including any embodiment or combination of embodiments described above, wherein the ingestible composition comprises a caloric sweetener, such as sucrose, fructose, xylitol, erythritol, or a combination thereof. In another related aspect, the present disclosure provides a concentrated sweetening composition comprising any of the flavor-modifying compounds of the above aspects and a sweetener, including any embodiment or combination of embodiments described above.

[0122] In certain embodiments of any of the aspects and embodiments described herein that refer to an ingestible composition, the ingestible composition is a non-naturally occurring product, e.g., a flavored product, such as a composition specially manufactured for the production of a food or beverage product.

[0123] Generally, the compounds disclosed and described herein can be provided individually or in combination in a composition, e.g., an ingestible composition. In one embodiment, the compounds disclosed and described herein can be provided individually or in combination to impart a more sugar-like temporal or flavor profile to a sweetener composition by combining one or more compounds disclosed and described herein with one or more sweeteners in a sweetening composition. In another embodiment, the compounds disclosed and described herein can be provided individually or in combination to increase or enhance the sweetness of a composition by contacting the composition with a compound disclosed and described herein to form an improved composition.

[0124] In certain embodiments, the ingestible composition comprises sucrose and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less sucrose (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more sucrose. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as soda, etc. The sucrose can be introduced in any suitable form, such as natural syrup (sugar cane syrup), etc.

[0125] In certain embodiments, the ingestible composition comprises fructose and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less fructose (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more fructose. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda. Fructose can be provided in any suitable form, such as natural syrup, high fructose corn syrup, and the like.

[0126] In certain embodiments, the ingestible composition comprises high fructose corn syrup and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less high fructose corn syrup (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more high fructose corn syrup. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda.

[0127] In certain embodiments, the ingestible composition comprises glucose (e.g., D-glucose, either its alpha or beta form, or a combination thereof) and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less glucose (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more glucose. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda. The glucose can be introduced in any suitable form, such as a natural syrup.

[0128] In certain embodiments, the ingestible composition comprises sucralose and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less sucralose (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more sucralose. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda.

[0129] In certain embodiments, the ingestible composition comprises a rebaudioside (e.g., rebaudioside A, rebaudioside D, rebaudioside E, rebaudioside M, or any combination thereof) and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less rebaudioside (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a level of sweetness characteristic equivalent to products using more rebaudioside. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda.

[0130] In certain embodiments, the ingestible composition comprises acesulfame K and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less acesulfame K (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more acesulfame K. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda.

[0131] In certain embodiments, the ingestible composition comprises allulose and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less allulose (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of the same characteristics as a product using more allulose. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda.

[0132] In certain embodiments, the ingestible composition comprises erythritol and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less erythritol (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more erythritol. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda.

[0133] In certain embodiments, the ingestible composition comprises aspartame and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less aspartame (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more aspartame. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda.

[0134] In certain embodiments, the ingestible composition comprises cyclamate and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less cyclamate (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a sweetness level of comparable characteristics to products using more cyclamate. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda.

[0135] In certain embodiments, the ingestible composition comprises a mogroside (e.g., mogroside III, mogroside IV, mogroside V, chamenoside, isomogroside V, mogroside IVE, isomogroside V, mogroside IIIE, 11-oxomogroside V, the alpha isomer of isomogroside V, and any combination thereof) and a flavor-modifying compound. In some such embodiments, the incorporation of the flavor-modifying compound allows for the use of less mogroside (e.g., more than 10% less, more than 20% less, more than 30% less, more than 40% less, more than 50% less, more than 60% less, or more than 70% less) while still achieving a level of sweetness characteristically comparable to products using more mogroside. In some embodiments, the concentration of the flavor-modifying compound is 1000 ppm or less, or 900 ppm or less, or 800 ppm or less, or 700 ppm or less, or 600 ppm or less, or 500 ppm or less, or 400 ppm or less, or 300 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 25 ppm or less, or 10 ppm or less. Such ingestible compositions may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically described below. In other embodiments, the ingestible composition is a beverage product, such as a soda. Additional mogroside compounds that may be suitably used are described in U.S. Patent Application Publication No. 2017 / 0119032.

[0136] Thus, in some embodiments, the composition of any of the above aspects (including any use or method) comprises a flavor-modifying compound and a sweetener. In some embodiments, the composition further comprises an excipient. In some embodiments, the excipient is water. In some embodiments, the flavor-modifying compound is present at a concentration below its sweetness perception threshold.

[0137] For example, in some embodiments, the sweetener is present in an amount of about 0.1% to about 12% by weight. In some embodiments, the sweetener is present in an amount of about 0.2% to about 10% by weight. In some embodiments, the sweetener is present in an amount of about 0.3% to about 8% by weight. In some embodiments, the sweetener is present in an amount of about 0.4% to about 6% by weight. In some embodiments, the sweetener is present in an amount of about 0.5% to about 5% by weight. In some embodiments, the sweetener is present in an amount of about 1% to about 2% by weight. In some embodiments, the sweetener is present in an amount of about 0.1% to about 5% by weight. In some embodiments, the sweetener is present in an amount of about 0.1% to about 4% by weight. In some embodiments, the sweetener is present in an amount of about 0.1% to about 3% by weight. In some embodiments, the sweetener is present in an amount of about 0.1% to about 2% by weight. In some embodiments, the sweetener is present in an amount of about 0.1% to about 1% by weight. In some embodiments, the sweetener is present in an amount of about 0.1% to about 0.5% by weight. In some embodiments, the sweetener is present in an amount of about 0.5% to about 10% by weight. In some embodiments, the sweetener is present in an amount of about 2% to about 8% by weight. In some further embodiments of the embodiments described in this paragraph, the sweetener is sucrose, fructose, glucose, xylitol, erythritol, or a combination thereof.

[0138] In some other embodiments, the sweetener is present in an amount between 10 ppm and 1000 ppm. In some embodiments, the sweetener is present in an amount between 20 ppm and 800 ppm. In some embodiments, the sweetener is present in an amount between 30 ppm and 600 ppm. In some embodiments, the sweetener is present in an amount between 40 ppm and 500 ppm. In some embodiments, the sweetener is present in an amount between 50 ppm and 400 ppm. In some embodiments, the sweetener is present in an amount between 50 ppm and 300 ppm. In some embodiments, the sweetener is present in an amount between 50 ppm and 200 ppm. In some embodiments, the sweetener is present in an amount between 50 ppm and 150 ppm. In some further embodiments of the embodiments described in this paragraph, the sweetener is a steviol glycoside, a mogroside, a derivative of any of the foregoing, e.g., a glycoside derivative (e.g., glucosylates), or any combination thereof.

[0139] The composition may include any suitable sweetener or combination of sweeteners. In some embodiments, the sweetener is a conventional sugar sweetener, such as sucrose, fructose, glucose, and a sweetener composition containing natural sugars, such as corn syrup (including high-fructose corn syrup) or other syrups, or a sweetener concentrate derived from natural fruit and vegetable sources. In some embodiments, the sweetener is sucrose, fructose, or a combination thereof. In some embodiments, the sweetener is sucrose. In some other embodiments, the sweetener is selected from rare natural sugars, including D-allose, D-psicose, L-ribose, D-tagatose, L-glucose, L-fucose, L-albinose, D-turanose, and D-leucrose. In some embodiments, the sweetener is selected from semi-synthetic "sugar alcohol" sweeteners, such as erythritol, isomalt, lactitol, mannitol, sorbitol, xylitol, maltodextrin, etc. In some embodiments, the sweetener is selected from artificial sweeteners such as aspartame, saccharin, acesulfame K, cyclamate, sucralose, and alitame. In some embodiments, the sweetener is selected from the group consisting of cyclamic acid, mogrosides, tagatose, maltose, galactose, mannose, sucrose, fructose, lactose, neotame and other aspartame derivatives, glucose, D-tryptophan, glycine, maltitol, lactitol, isomalt, hydrogenated glucose syrup (HGS), hydrogenated starch hydrolysates (HSH), stevioside, rebaudioside A, other sweet stevia-based glycosides, chemically modified steviol glycosides (e.g., glucosylated steviol glycosides), mogrosides, chemically modified mogrosides (e.g., glucosylated mogrosides), karerame, 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 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 is a sugar. In some embodiments, the sugar is sucrose. In some embodiments, the sugar is sugar 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.

[0140] Sweeteners may also include, for example, sweetener compositions comprising one or more natural or synthetic carbohydrates, such as corn syrup, high fructose corn syrup, high maltose corn syrup, glucose syrup, sucralose syrup, hydrogenated glucose syrup (HGS), hydrogenated starch hydrolysates (HSH), or other syrups or sweetener concentrates derived from natural fruit and vegetable sources, or semi-synthetic "sugar alcohol" sweeteners, such as polyols. Non-limiting examples of polyols in some embodiments include erythritol, maltitol, mannitol, sorbitol, lactitol, xylitol, isomalt, propylene glycol, glycerol (glycerin), threitol, galactitol, palatinose, reduced isomaltooligosaccharides, reduced xylo-oligosaccharides, reduced gentio-oligosaccharides, reduced maltose syrup, reduced glucose syrup, isomaltulose, maltodextrin, and the like, as well as sugar alcohols or other carbohydrates, or combinations thereof that can be reduced without adversely affecting taste.

[0141] Sweeteners may be natural or synthetic sweeteners, including, but not limited to, agave inulin, agave nectar, agave syrup, amazake, brazzein, brown rice syrup, coconut crystals, coconut sugar, coconut syrup, date sugar, fructans (also known as inulin fiber, fructooligosaccharides, or oligo-fructose), green stevia powder, stevia rebaudiana Ana, 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 Artichoke syrup, licorice root, Monk fruit (fruit, powder, or extract), Lucuma (fruit, powder, or extract), maple sap (including sap extracted from, for example, sugar maple (Acer saccharum), black maple (Acer nigrum), red maple (Acer rubrum), silver maple (Acer saccharinum), Norway maple (Acer platanoides), ash maple (Acer negundo), bigleaf maple (Acer macrophyllum), bigleaf maple (Acer grandidentatum), rocky mountain maple (Acer glabrum), and silver maple (Acer mono)), maple syrup, maple sugar, walnut sap (for example, white walnut (Juglans cinerea), black walnut (Juglans nigra), and Japanese walnut (Juglans ailatifolia, including sap extracted from Japanese walnut (Juglans regia), birch sap (e.g., American white birch (Betula papyrifera), yellow birch (Betula alleghaniensis), American beetle (Betula lenta), river birch (Betula nigra), gray birch (Betula populifolia), and silver birch (Betulapendula), sycamore maple sap (e.g., sap extracted from American sycamore maple (Platanus occidentalis), ironwood sap (e.g., sap extracted from American asada (Ostrya virginiana)), muscovado, molasses (e.g., blackstrap molasses), molasses sugar, monatin, monellin, sucrose (also known as natural sugar, unrefined sucrose, or sucrose), palm sugar, raw sugar, piloncillo, rapadura, raw sugar, rice syrup, sorghum, sorghum syrup, cassava syrup (also known as tapioca syrup), thaumatin, yacon root, malt syrup, barley malt syrup, barley malt powder, sugar beet sugar, sucrose, crystalline juice crystals), caramel, carbitol, carob syrup, castor sugar, hydrogenated starch hydrolysate, hydrolyzed canned juice, hydrolyzed starch, invert sugar, anethole, arabinogalactan, arop, syrup, P-4000, acesulfame potassium (also known as acesulfame K or ace-K), alitame (also known as acrame), advantame, aspartame, bayunoside, neotame, benzamide derivatives, bernadam, canderel, karerame and other guanidine-based sweeteners, vegetable fiber, corn sugar, coupling sugar, Curculin, cyclamate, cyclocaryoside I, demerara, dextran, dextrin, saccharified malt, dulcin, sucrose, valgin, dulcoside A, dulcoside B, emulin, enoxolone, maltodextrin, saccharin, estragole, ethyl maltol, glucine, gluconic acid, gluconolactone, glucosamine, glucoronic acid, glycerol, glycine, glycyphilin, glycyrrhizin, glycyrrhetinic acid monoglucuronide, golden sugar, yellow sugar, golden syrup, granulated sugar, Jiaogulan, hernandurcin, Isomerized liquid sugar, jalab, chicory root dietary fiber, kynurenine derivatives (including N'-formyl-kynurenine, N'-acetyl-kynurenine, 6-chloro-kynurenine), galactitol, ritesse, lydican, lycasin, ragduname, guanidine, falernum, mabinlin I, mabinlin II, maltol, multisorb, maltodextrin, maltotriol, mannosamine, miraculin, starch syrup, mogrosides (including mogroside IV, mogroside V, and neomogroside), mukuroziosides, nanosugar, naringin Dihydrochalcone, Neohesperidin Dihydrochalcone, Nib Sugar, Nigerooligosaccharide, Norbu, Orje Syrup, Osladin, Pekmez, Pentasin, Periandrin I, Perillaldehyde, Perillartine, Petophyllum, Phenylalanine, Phlomisoside I, Phlologizin, Phyllodulcin, Polyglycitol Syrup, Polypodoside A, Pterocaryoside A, Pterocaryoside B, Rebiana, Refiner Syrup, Rub Syrup, Rubusoside, Serigeain A, Sugrue, Shamenoside I, Siraitia grosvenorii), soy oligosaccharides, Splenda, SRI oxime V, steviol glycosides, steviolbioside, stevioside, strogin 1, 2 and 4, sucronate, sucrose, suosan, phloridzin, super aspartame, tetrasaccharide, threitol, treacle, trilobutene, tryptophan and derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, volemitol, birch syrup, aspartame-acesulfame, asguline, and combinations or blends of any two or more thereof.

[0142] In yet other embodiments, the sweetener may be a chemically or enzymatically modified natural high-potency sweetener. Modified natural high-potency sweeteners include glycosylated natural high-potency sweeteners, such as glucosyl, galactosyl, or fructosyl derivatives containing 1 to 50 glycoside residues. Glycosylated natural high-potency sweeteners may be prepared by enzymatic transglycosylation catalyzed by various enzymes exhibiting transglycosylation activity. In some embodiments, the modified sweetener may be substituted or unsubstituted.

[0143] Additional sweeteners also include any combination of two or more of the foregoing sweeteners. In some embodiments, the sweetener may include a combination 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 with other natural and artificial sweeteners. In some embodiments, the sweetener is a caloric sweetener, such as sucrose, fructose, xylitol, erythritol, or a combination thereof. In some embodiments, the ingestible composition is free of, or (in some embodiments) substantially free of, stevia-derived sweeteners, such as steviol glycosides, glucosylated steviol glycosides, or rebaudiosides. For example, in some embodiments, the ingestible composition either does not contain stevia-derived sweeteners, or contains stevia-derived sweeteners at a concentration of 1000 ppm or less, or 500 ppm or less, or 200 ppm or less, or 100 ppm or less, or 50 ppm or less, or 20 ppm or less, or 10 ppm or less, or 5 ppm or less, or 3 ppm or less, or 1 ppm or less.

[0144] The flavor-modifying compound may be present in the ingestible composition in any suitable amount. In some embodiments, the flavor-modifying compound is present in an amount sufficient to enhance the taste of the composition (e.g., enhance sweetness, reduce sourness, or reduce bitterness). Thus, in some embodiments, the ingestible composition comprises the flavor-modifying compound at a concentration of 200 ppm or less, or 150 ppm or less, or 100 ppm or less, or 50 ppm or less, or 40 ppm or less, or 30 ppm or less, or 20 ppm or less. In some embodiments, the flavor-modifying compound is present in a minimal amount, for example, 1 ppm or 5 ppm. Thus, in some embodiments, the ingestible composition comprises the flavor-modifying compound at a concentration ranging from 1 ppm to 200 ppm, or from 1 ppm to 150 ppm, or from 1 ppm to 100 ppm, or from 1 ppm to 50 ppm, or from 1 ppm to 40 ppm, or from 1 ppm to 30 ppm, or from 1 ppm to 20 ppm, or from 5 ppm to 200 ppm, or from 5 ppm to 150 ppm, or from 5 ppm to 100 ppm, or from 5 ppm to 50 ppm, or from 5 ppm to 40 ppm, or from 5 ppm to 30 ppm, or from 5 ppm to 20 ppm. In embodiments in which a sweetener, such as sucrose or fructose, is present, the weight to weight ratio of sweetener to flavor-modifying compound in the ingestible composition is in the range of from 1000:1 to 5000:1, or from 1000:1 to 10000:1, or from 2000:1 to 8000:1.

[0145] The ingestible composition or sweetener concentrate may, in certain embodiments, include any additional ingredient or combination of ingredients as conventionally used in food and beverage products, including, but not limited to: Acids including, for example, citric acid, phosphoric acid, ascorbic acid, sodium acid sulfate, lactic acid, or tartaric acid; bitter components including, for example, caffeine, quinine, green tea, catechins, polyphenols, green robusta coffee extract, green coffee extract, potassium chloride, menthol, or proteins (e.g., proteins and protein isolates derived from plants, algae, or fungi); Colorants, such as caramel color, 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 including, for example, sodium benzoate, potassium benzoate, potassium sorbate, sodium metabisulfate, sorbic acid, or benzoic acid; antioxidants, including, for example, ascorbic acid, calcium disodium EDTA, alpha tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol, or sodium hexametaphosphate; Vitamins or functional ingredients, such as resveratrol, Co-Q10, omega-3 fatty acids, theanine, choline chloride (cytocholine), Fibersol, inulin (chicory root), taurine, ginseng extract, guanana extract, ginger extract, L-phenylalanine, L-carnitine, L-tartrate, D-glucoronolactone, inositol, bioflavonoids, echinacea, ginkgo biloba, yerba mate, flaxseed oil, garcinia cambogia rind extract, white tea extract, ribose, milk thistle thistle) extract, grape seed extract, pyrodixine HCl (vitamin B6), cyanobalamin (vitamin B12), niacinamide (vitamin B3), biotin, calcium lactate, calcium pantothenate (pantothenic acid), calcium phosphate, calcium carbonate, chromium chloride, chromium polynicotinate, ferric sulfate, folic acid, ferric pyrophosphate, iron, magnesium lactate, magnesium carbonate, magnesium sulfate, monopotassium phosphate, monosodium phosphate, phosphorus, potassium iodide, potassium phosphate, riboflavin, sodium sulfate, Vitamins or functional ingredients, including sodium gluconate, sodium polyphosphate, sodium bicarbonate, thiamine mononitrate, vitamin D3, vitamin A palmitate, zinc gluconate, zinc lactate, or zinc sulfate; Clouding agents, including, for example, ester gun, brominated vegetable oil (BVO), or sucrose acetate isobutyrate (SAIB); For example, sodium citrate, potassium citrate, or buffers containing salts; For example, propylene glycol, ethyl alcohol, glycerin, gum arabic (gum acacia), maltodextrin, modified corn starch, dextrose, natural flavors, natural flavors with other natural flavors (natural flavors WONF), natural and artificial flavors, flavors containing artificial flavors, silicon dioxide, magnesium carbonate, or tricalcium phosphate; or For example, starches and stabilizers including pectin, xanthan gum, carboxymethyl cellulose (CMC), polysorbate 60, polysorbate 80, medium chain triglycerides, cellulose gel, cellulose gum, sodium caseinate, modified food starch, gum arabic (gum arabic), inulin, or carrageenan.

[0146] The ingestible composition or sweetener concentrate can have any suitable pH. In some embodiments, the flavor-modifying compound enhances the sweetness of a sweetener over a wide range of pH, for example, from lower to neutral pH. Lower and neutral pH includes, but is not limited to, pHs from about 2.5 to about 8.5, from about 3.0 to about 8.0, from about 3.5 to about 7.5, and from about 4.0 to about 7. In certain embodiments, the compounds disclosed and described herein, individually or in combination, can enhance the perceived sweetness of a fixed concentration of a sweetener in a taste test at compound concentrations of about 50 μM, 40 μM, 30 μM, 20 μM, or 10 μM at both low and neutral pH values. In certain embodiments, the enhancement factor of the compounds disclosed and described herein, individually or in combination, at lower pH is substantially similar to the enhancement factor of the compounds at neutral pH. Such consistent sweetness enhancing properties over a wide range of pH allow for broad use of the compounds disclosed and described herein, individually or in combination, in a wide variety of foods and beverages.

[0147] The ingestible compositions provided according to any of the above embodiments, in certain embodiments, comprise one or more additional flavor-modifying compounds, such as a compound that enhances sweetness (e.g., hesperetin, neohesperetin, phloretin, naringenin, glucosylated steviol glycosides, etc.), a compound that blocks bitterness, a compound that enhances umami, a compound that reduces sourness or licorice taste, a compound that enhances saltiness, a compound that enhances cooling effect, or any combination of the foregoing.

[0148] The ingestible compositions provided according to any of the above embodiments, in certain embodiments, comprise one or more additional flavor-modifying compounds, such as a compound that enhances sweetness (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), a compound that blocks bitterness, a compound that enhances umami, a compound that reduces sourness or licorice taste, a compound that enhances saltiness, a compound that enhances cooling effect, or any combination of the foregoing.

[0149] Thus, in some embodiments, ingestible compositions disclosed herein include a flavor-modifying compound according to any of the foregoing embodiments or combinations of embodiments, in combination with one or more other sweetness-enhancing compounds, including, but not limited to, naturally occurring compounds such as hesperetin, naringenin, glucosylated steviol glycosides, or synthetic compounds such as any of the compounds 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, and U.S. Patent Application Publication No. 2017 / 0119032. The flavor modifying compounds may be combined with such other sweetness enhancers in any suitable ratio (w / w) ranging from 1:100 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, e.g., 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1: The flavor-modifying compound may be used in a ratio of 1:13, 1:12, 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1. In some embodiments of any of the foregoing embodiments, the flavor-modifying compound is combined with the glucosylated steviol glycoside in any of the foregoing ratios. As used herein, the term "glucosylated steviol glycoside" refers to the product of enzymatic glucosylation of a naturally occurring steviol glycoside compound. Glucosylation generally occurs via glycosidic bonds, such as α-1,2, α-1,4, α-1,6, β-1,2, β-1,4, β-1,6, and the like.In some embodiments of any of the foregoing embodiments, the TM1 compound (or any food-acceptable salt thereof) is combined with N-(1-((4-amino-2,2-dioxo-1H-benzo[c][1,2,6]thiadiazin-5-yl)oxy)-2-methyl-propan-2-yl)isonicotinamide in any of the foregoing ratios.

[0150] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor-modifying compound according to any of the foregoing embodiments or combinations of embodiments, in combination with one or more umami-enhancing compounds, including, but not limited to, naturally occurring compounds such as ericamide, or synthetic compounds such as any of the compounds described in U.S. Patent Nos. 8,735,081, 8,124,121, and 8,968,708. The flavor modifying compounds may be combined with such palatability enhancers in any suitable ratio (w / w) ranging from 1:100 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, such as 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:1 1:3, 1:12, 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0151] In some further embodiments, ingestible compositions disclosed herein comprise a flavor-modifying compound according to any of the foregoing embodiments or combinations of embodiments, in combination with one or more cooling enhancing compounds, including, but not limited to, naturally occurring compounds such as menthol or analogs thereof, or synthetic compounds, such as any of the compounds described in U.S. Patent Nos. 9,394,287 and 10,421,727. The flavor modifying compounds may be combined with such cooling enhancers in any suitable ratio (w / w) in the range of 1:100 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, e.g., 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:1 1:3, 1:12, 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0152] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor-modifying compound according to any of the foregoing embodiments or combinations of embodiments, in combination with one or more bitter-blocking compounds, including, but not limited to, naturally occurring compounds such as menthol or analogs thereof, or synthetic compounds such as any of the compounds described in U.S. Patent Nos. 8,076,491, 8,445,692, and 9,247,759. The flavor modifying compounds may be combined with such bitterness blockers in any suitable ratio (w / w) in the range of 1:100 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, e.g., 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:1 1:3, 1:12, 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0153] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor modifying compound according to any of the foregoing embodiments or combinations of embodiments, in combination with one or more acidity regulating compounds. The flavor modifying compound may be combined with such other acidity regulating compounds in any suitable ratio (w / w) ranging from 1:100 to 1000:1, or from 1:100 to 100:1, or from 1:50 to 50:1, or from 1:25 to 25:1, or from 1:10 to 10:1, such as 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, 1:46, 1:47, 1:48, 1:49, 1:50, 1:51, 1:52, 1:53, 1:54, 1:55, 1:56, 1:57, 1:58, 1:59, 1:60, 1:61, 1:62, 1:63, 1: 1:13, 1:12, 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0154] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor-modifying compound according to any of the foregoing embodiments or combinations of embodiments, in combination with one or more mouthfeel-altering compounds. Such mouthfeel-altering compounds include, but are not limited to, tannins, cellulosic materials, bamboo powder, etc. The flavor-modifying compound may be combined with such mouthfeel enhancers in any suitable ratio (w / w) ranging from 1:100 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, such as 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1: 1:13, 1:12, 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0155] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor-modifying compound according to any of the foregoing embodiments or combinations of embodiments, in combination with one or more flavor-masking compounds. Such flavor-masking compounds include, but are not limited to, cellulosic materials, fungal extracts, plant extracts, citric acid, carbonic acid (or carbonate salts), and the like. The flavor-modifying compound may be combined with such flavor-masking enhancers in any suitable ratio (w / w) ranging from 1:100 to 1000:1, or 1:100 to 100:1, or 1:50 to 50:1, or 1:25 to 25:1, or 1:10 to 10:1, such as 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, It may be used at a ratio of 1:13, 1:12, 1:11, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, or 25:1.

[0156] In some aspects related to the above aspects and embodiments, the present disclosure provides the use of a flavor modifying compound to enhance the flavor of a flavored composition, e.g., a flavored product. Such a flavored composition can use any suitable flavor, e.g., any of the flavors described above.

[0157] Flavored products and concentrates In certain aspects, the present disclosure provides a flavored product comprising the composition of any of the five aspects. In some embodiments, the flavored product is a beverage product, such as soda, flavored water, and tea. In some embodiments, the flavored product is a food product, such as yogurt.

[0158] In embodiments in which 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 drink, nectar, vegetable juice, vegetable flavored juice, sports drink, energy drink, fortified water drink, vitamin fortified water, near water drink, coconut water, tea-type drink, coffee, cocoa drink, dairy beverage, cereal extract beverage, and smoothie. In some embodiments, the beverage may be a soft drink.

[0159] In certain embodiments of any of the aspects and embodiments described herein that refer to a flavored product, the flavored product is a non-naturally occurring product, such as a packaged food or beverage product.

[0160] Further non-limiting examples of food and beverage products or formulations include sweet coatings, frostings or glazes for such products, or any entity included in the soup category, the dried prepared foods category, the beverage category, the ready meal category, the canned or preserved foods category, the frozen prepared foods category, the refrigerated prepared foods category, the snack foods category, the baked goods category, the confectionery category, the dairy category, the ice cream category, the meal replacement category, the pasta and noodle category, and the sauces, dressings, condiments category, the baby food category, and / or the spreads category.

[0161] Generally, the soup category refers to canned / preserved, dehydrated, instant, refrigerated, UHT, and frozen soups. For purposes of this definition, soup means a food prepared from meat, poultry, fish, vegetables, grains, fruit, and other ingredients and cooked in a liquid that may contain some or all visible parts of these ingredients. It may be clear (like bouillon) or thick (like chowder), smooth, pureed, or chunky, ready-to-use, semi-condensed, or condensed, and may be served hot or cold, as a first or main course of a meal, or as a snack (sipped like a drink) between meals. Soup may be used as an ingredient for preparing other meal ingredients and may vary from bouillons (consommes) to sauces (cream- or cheese-based soups).

[0162] The dehydrated and cooking food category generally refers to: (i) cooking aid products, such as powders, granules, pastes, concentrated liquid products (including concentrated bouillons, bouillons, and bouillon-like products in compressed cube, tablet, powder, or granule form, sold separately as finished products or as an ingredient in products), sauces, and recipe mixes (regardless of technology); (ii) meal solution products, such as dehydrated and freeze-dried soups (including dehydrated soup mixes, dehydrated instant soups, dehydrated cooked soups, and dehydrated or circumstantial cooking of ready-to-eat dishes), meals, and single-serve entrees (including pasta, potato, and rice dishes); and (iii) meal garnish products, such as seasonings, marinades, salad dressings, salad toppings, dips, breads, batter mixes, shelf-stable spreads, barbecue sauces, liquid recipe mixes, concentrates, sauces, or sauce mixes (including recipe mixes for salads, whether dehydrated, liquid, or frozen, sold as finished products or as an ingredient in products).

[0163] The beverage category generally refers to beverages, beverage mixes, and concentrates, including, but not limited to, carbonated and non-carbonated beverages, alcoholic and non-alcoholic beverages, ready-to-drink beverages, liquid concentrate formulations for preparing beverages, such as soda, and dry powdered 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 / perry, FAB, wine, and spirits. Soft drinks include carbonated, e.g., cola and non-cola carbonated; fruit juices, e.g., juices, nectars, juice drinks, and fruit-flavored beverages; bottled waters, including sparkling water, spring water, and purified / table water; functional beverages, which may be carbonated or distilled, including sports drinks, energy drinks, or elixir drinks; and concentrates, e.g., ready-to-drink liquid and powder concentrates. Drinks, either hot or cold, include, but are not limited to, coffee or iced coffee, such as fresh coffee, instant coffee, and coffee combinations; tea or iced tea, such as black tea, green tea, white tea, oolong tea, flavored tea; and other drinks, including flavored, malt, or plant-based powders, granules, blocks, or tablets mixed with milk or water.

[0164] The snack food category generally refers to any food that can be a light, casual meal, including, but not limited to, sweet and savory snacks and snack bars. Examples of snack foods include, but are not limited to, fruit snacks, chips / crisps, extruded snacks, tortilla / corn chips, popcorn, pretzels, nuts, and other sweet and savory snacks. Examples of snack bars include, but are not limited to, granola / muesli bars, breakfast bars, energy bars, fruit bars, and other snack bars.

[0165] The category of baked goods generally refers to any edible product whose preparation involves a process of heat or exposure to excessive sunlight. Examples of baked goods include, but are not limited to, bread, buns, cookies, muffins, cereals, toaster pastries, pastries, waffles, tortillas, biscuits, pies, bagels, tarts, quiches, cakes, any baked goods, and any combination thereof.

[0166] 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 artisanal ice cream; soy, oat, pea (e.g., adzuki bean, mung bean), and rice-based ice cream.

[0167] The confectionery category generally refers to edible products that are sweet in taste. Examples of confectionery include, but are not limited to, candy, gelatin, chocolate confectionery, sugar confectionery, gum, and the like, and any combination thereof.

[0168] The meal replacement category generally refers to any food product intended to replace a regular meal, especially for health or fitness conscious people. Examples of meal replacements include, but are not limited to, slimming products and recovery products.

[0169] The ready meal category generally refers to any food that can be served as a meal without extensive preparation or processing. Ready meals include products with the "skill" of a recipe attached by the manufacturer, providing a high degree of preparation, perfection, and convenience. Examples of ready meals include, but are not limited to, canned / preserved, frozen, dried, and refrigerated ready meals; dinner mixes; frozen pizza; refrigerated pizza; and pre-prepared salads.

[0170] The pasta and noodles category includes pasta and / or noodles, including, but not limited to, canned, dried, refrigerated / fresh pasta; and plain, instant, frozen, refrigerated, and snack noodles.

[0171] The canned / preserved food category includes, but is not limited to, canned / preserved meat and meat products, fish / seafood, vegetables, tomatoes, beans, fruit, ready meals, soups, pasta, and other canned / preserved foods.

[0172] The frozen processed food category includes, but is not limited to, frozen processed red meat, processed poultry, processed fish / seafood, processed vegetables, meat substitutes, processed potatoes, bakery products, desserts, ready meals, pizza, soups, noodles, and other frozen foods.

[0173] The dry processed food category includes, but is not limited to, rice, dessert mixes, dried ready meals, dehydrated soups, instant soups, dried pasta, plain noodles, and instant noodles. The refrigerated processed food category includes, but is not limited to, refrigerated processed meats, processed fish / seafood products, lunch kits, fresh cut fruit, ready meals, pizza, pre-prepared salads, soups, and fresh pasta and noodles.

[0174] The sauces, dressings and condiments category includes, but is not limited to, tomato paste and puree, bouillon / stock cubes, herbs and spices, monosodium glutamate (MSG), table sauces, soy-based sauces, pasta sauces, wet / cooking sauces, dry sauces / powder mixes, ketchup, mayonnaise, mustard, salad dressings, vinaigrettes, dips, pickles, and other sauces, dressings and condiments.

[0175] The baby food category includes, but is not limited to, milk-based or soy-based formulas; and cooked, dried, and other baby foods.

[0176] The spreads category includes, but is not limited to, jams and preserves, honey, chocolate spreads, nut-based spreads, and yeast-based spreads.

[0177] The dairy category generally refers to edible products made from mammalian milk. Examples of dairy products include, but are not limited to, milk products, cheese, yogurt and sour milk drinks, and other dairy products.

[0178] Further examples of flavored products, particularly food and beverage products or formulations, are given below. Exemplary ingestible compositions include one or more of confectionery, chocolate confectionery, tablets, count lines, bagged self-lined / soft lines, boxed assortments, standard boxed assortments, twist wrapped miniatures, seasonal chocolates, toy chocolates, alfajores, other chocolate confectionery, mints, standard mints, power mints, boiled confectionery, pastilles, gum, jellies and chews, toffee, caramel and nougat, medicated confectionery, lollipops, licorice, other sugar confectionery, bread, bagged / factory-made bread, bagged / factory-made bread, pastries, cakes, bagged / factory-made cakes, bagged / factory-made cakes, cookies, chocolate coated biscuits, sandwich biscuits, filled biscuits, flavored biscuits and crackers, bread substitutes, breakfast cereal, rte cereal, family breakfast cereal, flakes, muesli, other cereals, children's breakfast cereal, hot cereal, ice cream, impulse ice cream, single portion dairy ice cream, single portion aqueous ice cream. Ice cream, multipack dairy ice cream, multipack water-based ice cream, take away ice cream, take away dairy ice cream, ice cream desserts, bulk ice cream, take away water-based ice cream, frozen yogurt, artisanal ice cream, dairy products, milk, raw / pasteurized milk, full fat raw / pasteurized milk, semi-skimmed fresh / pasteurized milk, long shelf life / uht milk, full fat long shelf life / uht milk, semi-skimmed long shelf life / uht milk, non-fat long shelf life / uht milk, goat milk, concentrated / evaporated milk, plain concentrated / evaporated milk, flavoured, functional and other concentrated milks, flavoured milk drinks, dairy only flavoured milk drinks, flavoured milk drinks with fruit juice, soy milk, sour milk drinks, fermented milk drinks, coffee whitener, powdered milk, flavoured powdered milk drinks, cream, cheese, processed cheese, spreadable processed cheese, non-spreadable processed cheese, raw cheese,Spreadable raw cheese, hard cheese, packaged hard cheese, unpackaged hard cheese, yogurt, plain / natural yogurt, flavored yogurt, fruit yogurt, probiotic yogurt, drinking yogurt, regular drinking yogurt, probiotic drinking yogurt, refrigerated and shelf stable desserts, dairy based desserts, soy based desserts, refrigerated snacks, fromage fries and quark, plain fromage fries and quark, flavored fromage fries and quark, flavored fromage fries and quark, sweet and savory snacks, fruit snacks, chips / crisps, extruded snacks, tortillas / corn chips, popcorn, pretzels, nuts, sweet and savory snacks, snack bars, granola bars, breakfast bars, energy bars, fruit bars, other snack bars, meal replacements, slimming products, recovery drinks, ready meals, canned ready meals, frozen ready meals, dried ready meals, refrigerated ready meals, dinner mixes, frozen pizza, refrigerated pizza, soups, canned soups, dehydrated snacks soup, instant soup, refrigerated soup, hot soup, frozen soup, pasta, canned pasta, dried pasta, refrigerated / fresh pasta, noodles, plain noodles, instant noodles, cup / bowl instant noodles, pouch instant noodles, chilled noodles, snack noodles, canned food, canned meat and meat products, canned fish / seafood, canned vegetables, canned tomatoes, canned beans, canned fruit, canned ready meals, canned soup, canned pasta, other canned food, frozen food, frozen processed red meat, frozen processed poultry, frozen processed fish / fish, frozen processed vegetables, frozen meat substitutes, frozen potatoes, oven baked potato chips, other Oven baked potato products, Non-oven baked 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, Dehydrated soups, Instant soups, Dried pasta, Plain noodles, Instant noodles, Cup / bowl instant noodles, Pouch instant noodles, Refrigerated foods, Refrigerated processed meat, Refrigerated fish / seafood products, Refrigerated processed fish, Refrigerated coated fish, Refrigerated smoked fish, Refrigerated lunch kits, Refrigerated ready meals, Refrigerated pizza, Refrigerated soup,Includes refrigerated / fresh pasta, refrigerated noodles, oils and fats, olive oil, vegetable 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, gravy granules, liquid stocks and fonds, herbs and spices, fermented sauces, soy-based sauces, pasta sauces, wet sauces, dry sauces / powder mixes, ketchup, mayonnaise, regular mayonnaise, mustard, salad dressings, regular salad dressings, low-fat salad dressings, vinaigrettes, dips, pickles, other sauces, dressings and condiments, milk powder, formula, standard formula, follow-on formula, toddler formula, hypoallergenic formula, prepared baby food, dry baby food, other baby food, spreads, jams and preserves, honey, chocolate spreads, nut-based spreads, yeast-based spreads. Exemplary ingestible compositions also include confectionery, bakery products, ice cream, dairy products, sweetened snacks, snack bars, meal replacements, ready meals, soups, pasta, noodles, canned foods, frozen foods, dried foods, refrigerated foods, fats and oils, baby foods, or spreads, or mixtures thereof. Exemplary ingestible compositions also include breakfast cereals, sweetened drinks, or solid or liquid concentrate compositions for preparing beverages, ideally to allow for reduced concentrations of known sugar sweeteners or artificial sweeteners.

[0179] Some embodiments provide chewable compositions that may or may not be intended to be swallowed. In some embodiments, the chewable compositions may be gums, chewing gums, sugared gums, sugarless gums, functional gums, bubble gums, or the like, comprising the compounds disclosed and described herein, individually or in combination.

[0180] Typically, at least a sweet taste receptor-modulating amount, a sweet taste receptor ligand-modulating amount, a sweet flavor-modulating amount, a sweet flavor-imparting amount, a sweet flavor-enhancing amount, or a therapeutically effective amount of one or more compounds of the present invention is added to an ingestible composition, optionally in the presence of a sweetener, such that the sweetness-altered ingestible composition has an increased sweetness, as judged by humans or animals generally through procedures generally known in the art, or, in the case of formulation testing, by a majority of a panel of at least eight human taste testers, compared to an ingestible composition prepared without the compounds of the present invention.

[0181] In some embodiments, the compounds disclosed and described herein, individually or in combination, modulate the sweetness or other taste characteristics of other natural or synthetic sweet tastants and ingestible compositions made therefrom. In one embodiment, the compounds disclosed and described herein, individually or in combination, can be used or provided at their ligand-enhanced concentrations. For example, the compounds disclosed and described herein, individually or in combination, can be present in amounts of 0.001 ppm to 100 ppm, or 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.

[0182] In some embodiments, the flavor-modifying compounds disclosed and described herein, individually or in combination, may be provided in a flavor concentrate formulation, suitable for subsequent processing to produce, for example, a ready-to-use (i.e., readily available) product. By "flavor concentrate formulation," we mean a formulation that must be reconstituted with one or more dilution media to form a ready-to-use composition. The term "ready-to-use composition" is used interchangeably herein with "ingestible composition," which refers to any substance that can be orally ingested, alone or with other substances, whether or not intended for consumption. In one embodiment, a ready-to-use composition includes a composition that may be directly consumed by humans or animals. A flavor concentrate formulation is typically used by mixing or diluting it with one or more dilution media, e.g., any consumable or ingestible ingredient or product, to impart or modify one or more flavors to the dilution media. Such a use process is often referred to as reconstitution. Reconstitution can be performed in a home or industrial setting. For example, a frozen fruit juice concentrate can be reconstituted by a consumer in their kitchen with water or another 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 large-scale industrial manufacturers to produce ready-to-use soft drinks. Because flavor concentrate formulations contain flavoring agents or flavor modifiers at higher concentrations than ready-to-use compositions, flavor concentrate formulations are typically not suitable for direct consumption without reconstitution. There are many advantages to using and producing flavor concentrate formulations. For example, one advantage is a reduction in weight and volume for transportation, since the flavor concentrate formulation can be reconstituted at the time of use by adding a suitable solvent, solid, or liquid.

[0183] The flavored products described according to any of the above embodiments, in certain embodiments, comprise one or more additional flavor-modifying compounds, such as a sweetness-enhancing compound (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), a bitterness-blocking compound, an umami-enhancing compound, a sourness-reducing compound, a saltiness-enhancing compound, a cooling effect-enhancing compound, or any combination of the foregoing.

[0184] In certain embodiments of any of the aspects and embodiments described herein that refer to a sweetening or flavoring concentrate, the sweetening or flavoring concentrate is a composition that is specially prepared for the production of a non-naturally occurring product, e.g., a flavored product, e.g., a food or beverage product.

[0185] In one embodiment, a flavor concentrate formulation comprises i) a compound disclosed and described herein, either individually or in combination, ii) a carrier, and iii) optionally at least one adjuvant. The term "carrier" refers to a typically inert auxiliary substance, such as a solvent, binder, or other inert medium, used in combination with a compound of the present invention and one or more optional adjuvants to form a formulation. For example, water or starch may be a carrier for a flavor concentrate formulation. In some embodiments, the carrier is the same as the dilution medium for reconstituting the flavor concentrate formulation, while in other embodiments, the carrier is different from the dilution medium. As used herein, the term "carrier" includes, but is not limited to, ingestible and acceptable carriers.

[0186] The term "adjuvant" refers to an additive that supplements, stabilizes, maintains, or enhances the intended function or effectiveness of an active ingredient, such as a compound of the present invention. In one embodiment, the at least one adjuvant comprises one or more flavoring agents. The flavoring agents may be any flavor known to those skilled in the art or consumers, such as chocolate, coffee, tea, mocha, French vanilla, peanut butter, chai, or combinations thereof. In another embodiment, the at least one adjuvant comprises one or more sweeteners. The one or more sweeteners may be any of the sweeteners described herein. In another embodiment, the at least one adjuvant comprises one or more ingredients selected from the group consisting of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, salts, and combinations thereof. Examples of emulsifiers, stabilizers, antimicrobial preservatives, antioxidants, vitamins, minerals, fats, starches, protein concentrates and isolates, and salts are described in U.S. Pat. No. 6,468,576, the contents of which are incorporated by reference in their entirety for all purposes.

[0187] In one embodiment, the flavor concentrate formulations of the present invention may be in a form selected from the group consisting of liquids, including solutions and suspensions, solids, foamable materials, pastes, gels, creams, and combinations thereof, e.g., liquids containing a certain amount of solids. In one embodiment, the flavor concentrate formulations are in the form of liquids, including aqueous and non-aqueous bases. In some embodiments, the flavor concentrate formulations of the present invention may be carbonated or non-carbonated.

[0188] The flavor concentrate formulation may further include at least one adjuvant: a freezing point depressant, a nucleating agent, or both. A freezing point depressant is an ingestible compound or agent capable of depressing the freezing point of a liquid or solvent to which the compound or agent is added. That is, a liquid or solution containing the freezing point depressant has a lower freezing point than a liquid or solvent without the freezing point depressant. In addition to depressing the initial freezing point, the freezing point depressant may also reduce the water activity of the flavor concentrate formulation. Examples of freezing point depressants include, but are not limited to, carbohydrates, oils, ethyl alcohol, polyols such as glycerol, and combinations thereof. A nucleating agent refers to an ingestible compound or agent capable of promoting nucleation. The presence of a nucleating agent in the flavor concentrate formulation can improve the mouthfeel of frozen blushes in frozen slushes and help maintain the physical properties and performance of the slush at freezing temperatures by increasing the number of desired ice crystal centers. Examples of nucleating agents include, but are not limited to, calcium silicate, calcium carbonate, titanium dioxide, and combinations thereof.

[0189] In one embodiment, the flavor concentrate formulation is formulated with a low water activity to extend shelf life. Water activity is the ratio of the vapor pressure of water in the formulation to the vapor pressure of pure water at the same temperature. In one embodiment, the flavor concentrate formulation has a water activity of less than about 0.85. In another embodiment, the flavor concentrate formulation has a water activity of less than about 0.80. In another embodiment, the flavor concentrate formulation has a water activity of less than about 0.75.

[0190] In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least twice the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least five times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least ten times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least fifteen times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least twenty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least thirty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least forty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least fifty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the present invention at a concentration that is at least sixty times the concentration of the compound in the ready-to-use composition. In one embodiment, the flavor concentrate formulation has a compound of the invention at a concentration that is up to 100 times the concentration of the compound in the ready-to-use composition.

[0191] The sweetness or flavor concentrate provided according to any of the above embodiments may, in certain embodiments, comprise one or more additional flavor-modifying compounds, such as a compound that enhances sweetness (e.g., hesperetin, naringenin, glucosylated steviol glycosides, etc.), a compound that masks bitterness (e.g., eriodictyol, homoeriodictyol, sterubin, and salts or glycoside derivatives thereof, and vanillyl lignans such as matairesinol and other compounds described in WO 2012 / 146584), a compound that enhances umami (e.g., rubemamine, rubesenamine, (E)-3-(3,4-dimethoxyphenyl)-N-(4-methoxyphenethyl)acrylamide, etc.), a compound that reduces sourness and / or licorice taste, a compound that enhances saltiness, a compound that enhances cooling effect, or any combination of the foregoing.

[0192] Methods and Manufacturing The compounds disclosed herein may be synthesized by the methods described below or by modifications of these methods. Modifications of the methodology include, among other things, temperatures, solvents, reagents, etc., known to those skilled in the art. Generally, during any of the processes for preparation of the compounds disclosed herein, it may be necessary or desirable to protect sensitive or reactive groups on any of the molecules concerned.

[0193] In certain aspects, the present disclosure provides methods for producing the flavor-modifying compounds of the aspects via an enzyme-catalyzed process. For example, in certain embodiments, the methods include providing a flavanone precursor, or a derivative thereof, having a hydrogen atom at the 3-position of the central flavanone bicyclic ring system. Non-limiting examples of suitable flavanone precursors include hesperetin, naringenin, eriodictyol, homoeriodictyol, sterubin, or any salt or glycoside thereof. In certain embodiments, the methods include reacting the flavanone precursor with one or more enzymes to provide a non-hydrogen substituent at the 3-position of the central flavanone bicyclic ring system to provide a 3-position functionalized flavanone compound. In some embodiments, the one or more enzymes provide functionalization in a specific stereochemistry, such as R or S. The one or more enzymes can provide any suitable functionalization. In some embodiments, the one or more enzymes provide a hydroxyl (—OH) group at the 3-position. In some embodiments, this functionalization can be performed by the enzyme flavanone 3-hydroxylase. In some embodiments, the 3-functionalized flavanone compound is further functionalized at the 3-position. For example, in some embodiments where the 3-functionalized flavanone compound has a hydroxyl group at the 3-position, the hydroxyl group can be further functionalized using any reagent suitable for reacting with a hydroxyl group. For example, in some such embodiments, the hydroxyl group at the 3-position is reacted with a carboxylic acid, such as acetic acid, to form an ester (e.g., acetate). In some such embodiments, the further functionalization is performed in a manner that preserves the absolute stereochemistry at the 3-position.

[0194] In certain embodiments described above, the method includes providing naringenin (e.g., in a suitable solvent system); reacting naringenin with flavanone 3-hydroxylase to form aromadendrin [(2R,3R)-3,5,7,4'-tetrahydroxyflavanone]; and reacting aromadendrin with acetic acid (or an ester thereof) to form aromadendrin-3-O-acetate [(2R,3R)-3-acetoxy-5,7,4'-trihydroxyflavanone].

[0195] Example The following examples are included to further illustrate the present invention. Of course, these examples should not be construed as specifically limiting the invention. Variations of these examples within the scope of the claims are within the purview of one of ordinary skill in the art and are considered to be within the scope of the invention as described and claimed herein. The reader will recognize that one of ordinary skill in the art armed with this disclosure will be able to make and use the invention without the need for exhaustive examples.

[0196] Example 1 - Sweetness Enhancement The test compound, (2R,3R)-3-acetoxy-5,7,4'-trihydroxyflavanone (A01), was tested in comparison with naringenin for sweetness enhancement of a 5% (w / w) aqueous solution of sucrose. Taste panelists were asked to taste the following 5% sucrose solutions in Henniez water and rate their sweetness on a scale of 0 to 10, as well as the presence of licorice flavor in the samples on a scale of 0 to 10. The results are shown in Table 1.

[0197] [Table 1]

[0198] Example 2 - Sweetness Enhancement Test compound A01 was tested in comparison with other sweetness enhancers in a manner similar to that described in Example 1. The results are shown in Table 2. The comparative compounds were taxifolin 3-O-acetate (A02) and ampelopsin 3-O-acetate (A03).

[0199] [Table 2]

[0200] Example 3 - Sweetener Substitution Test Test Compound A01 was used in combination with certain sweeteners to provide a sweetness profile comparable to an equivalent beverage containing a higher concentration of sweetener and no amount of Test Compound A01.

[0201] In one study, 45 panelists were asked to choose between a beverage sweetened with 450 ppm rebaudioside M and a beverage containing 300 ppm rebaudioside M and 12 ppm test compound A01. Of the 45 panelists, 23 chose the former and 22 chose the latter, which is statistically equivalent. This indicated that the introduction of 12 ppm test compound A01 reduced the rebaudioside M concentration by 33%.

[0202] In another test, 45 panelists were asked to choose between a beverage sweetened with 160 ppm sucralose and a beverage containing 120 ppm sucralose and 12 ppm test compound A01. Of the 45 panelists, 22 chose the former and 23 chose the latter, which is statistically equivalent. This indicates that the introduction of 12 ppm test compound A01 can reduce the concentration of sucralose by 25%.

[0203] Example 4 - Preparation of compounds by biodegradation and chemical synthesis The following description illustrates non-limiting methods by which compound A01 was obtained.

[0204] Protein production The gene encoding flavanone-3-hydroxylase (F3H) from Arabidopsis thaliana (GenBank: U33932) was aligned with its original sequence (only the Cho restriction site was removed) and codon-optimized for E. coli with and without the Twist N-terminal Trx tag cloned into pET29a via the restriction sites NcoI and XhoI. E. coli BL21Star(DE3) was transformed with the four constructs.

[0205] For the preculture, 7 mL of LB medium containing kanamycin (50 μg / mL) was inoculated with the E. coli BL21Star(DE3) strain harboring the construct and incubated overnight at 37°C and 200 rpm. Five mL of the preculture was used to inoculate a 400 mL main culture of LB medium containing kanamycin (50 μg / mL) and incubated at 37°C until the optical density at 600 nm (OD600) reached approximately 0.8. Expression of AthF3H was induced with 0.1 mM IPTG (isopropyl-D-thiogalactopyranoside), and the culture was shaken at 20°C for 20 hours. Cells were harvested by centrifugation and resuspended in 100 mM potassium phosphate buffer (KPi, pH 7) to an OD of 50. Protein production was confirmed by SDS-PAGE, which showed that AthF3H was highly expressed as a soluble protein and there were no differences among the four constructs.

[0206] Biodegradation Biodegradation was carried out for 3 h in 50 mM Tris / HCl (pH 7) containing 10% MeOH, 4 mM (±)-naringenin, 10 mM α-ketoglutarate, 10 mM ascorbic acid, and 0.25 mM FeSO4 in a total volume of 150 mL with whole cells of E. coli BL21Star(DE3)-AthF3H at an OD of 10. The biomass was removed by centrifugation.

[0207] Purification of aromadendrin and unreacted naringenin The supernatant of the biodigestion was poured onto a pre-conditioned Waters Oasis HLB SPE cartridge (6 g). After completion of the retention period, the cartridge was rinsed with water and then eluted with three volumes of 100 mL of HO / EtOH (50:50) (Fr. 1-3) and three volumes of HO / EtOH (30:70) (Fr. 4-6). Fractions 1 and 2 were filtered, pooled, evaporated, and lyophilized to yield 102 mg of 90% pure aromadendrin (molar yield 59%). Similarly, fractions 4 and 5 yielded approximately 60 mg, which was pure unreacted naringenin. α D Measurement of the optical rotation of α = +21° (c = 0.5 g / 100 mL, EtOH) indicated that the unreacted naringin was (2R)-(+)-naringenin. Similarly, the produced aromadendrin was α D = +9° (c = 0.5 g / 100 mL, EtOH), and the major product was in the (2R,3R) configuration.

[0208] Synthesis of aromadendrin-3-O-acetate Aromadendrin (100 mg) and 10 mg of dimethylaminopyridine (DMAP) were diluted with pyridine (10 mL). Acetic anhydride (1 mL) was added dropwise. The reaction was stirred for 15 minutes. The pyridine was evaporated, and the reaction was taken up in 100 mL of EtOAc and washed with 5% KHSO4 and brine. It was dried over sodium sulfate and evaporated. The crude product was diluted with 10 mL of CHCl2 and cooled to 0 °C. Pyrrolidine (500 μL) was added in 100 μL portions, and the reaction was stirred at 0–10 °C for 2 hours. Dichloromethane (30 mL) was added, and the organic phase was washed successively with 5% KHSO4 and water. The aqueous phase was extracted twice with CHCl2. The combined organic phase was dried over sodium sulfate and evaporated. The crude product was purified by flash chromatography on a Lichroprep RP-18 (45 g glass column) using a water / acetonitrile 0.1% formic acid gradient (20%, 5 min, then 20-80% B in 20 min). Fractions containing the expected product were combined, evaporated, and lyophilized to give 53 mg of aromadendrin-3-O-acetate (59% yield). DMeasurement of the optical rotation of 0.5 g / 100 mL EtOH = +22.1° indicated the product was (2R,3R)-(+)-aromadendrin-3-O-acetate. 13 C (MeOD, 500 MHz): 20.2 (q); 73.8 (d); 82.5 (d); 96.6 (d); 97.7 (d); 102.2 (s); 116.3 (d); 127.9 (s); 130.2 (d); 159.7 (s); 164.3 (s); 165.5 (s); 169.1 (s); 170.9 (s); 193.4 (s)

[0209] Example 5 - Testing of natural mixtures In some cases, it may be desirable to obtain compound A01 from a natural source, where it may be extracted as a mixture with other flavonoid compounds.

[0210] Hydrolysis of Engelhardtia Roxburghiana extract In a 500 mL three-necked round-bottom flask equipped with a mechanical stirrer and a condenser, 25 g of Engelhardtia Roxburghiana extract (80% astilbene, supplied by Xi'an Tuofeng Biotech Ltd), 250 mL of 1 M citric acid (freshly prepared), and 250 mg of vitamin E were refluxed and stirred overnight. After cooling, the reaction mixture was extracted twice with ethyl acetate. The combined organic layers were washed once with deionized water and once with brine, dried over sodium sulfate, filtered, and evaporated to give 14.4 g of crude Engelhardtia hydrolysate (88.3% yield).

[0211] Acetylation of Engelhardtia hydrolysate by reactive distillation In a 500 mL three-neck round-bottom flask equipped with a 15 cm Vigreux, distillation bridge, and magnetic stirrer, 10 g of crude Engelhard Tier hydrolysate, 200 mL of AcOH, and approximately 100 mg of vitamin E were refluxed for 50 hours. The acetic acid was then distilled off, and the reaction mixture was diluted with approximately 200 mL of ethyl acetate. The organic phase was washed with 200 mL of 5% sodium bicarbonate, once with water, once with brine, dried over sodium sulfate, filtered, and evaporated to give 10 g of a tan powder (87.5% yield).

[0212] Flavonoid quantification The UPLC instrument was a Waters Acquity I-Class UPLC system consisting of a binary pump, PDA detector, column manager (four columns), fixed-loop sample manager, and ELSD detector. The mass spectrometer was a QExactivePlus (Thermo). The instrument was calibrated within 2 weeks using Thermo injection solution. The 4-P-FS-Engelhardtia-MeOH (previously described) method was used. For quantification, a secondary calibration curve was obtained using ions 305.0654 (1), 289.0706 (2), 347.0761 (3), and 331.0815 (4). The UV range used was 270–320 nm, resulting in a linear calibration curve. Samples were prepared by precisely dissolving 10.88 mg of 1, 10.15 mg of 3, 10.13 mg of 2, and 10.05 mg of 4 in 10.0 mL of ethanol. The stock solution was then diluted 10-fold in ethanol; this solution was the highest point of the calibration curve. Six calibration points were then created over the range of 100 ppm to 1 ppm (100:50:25:10:5:1). Approximately 10.0 mg of the resulting mixture was diluted with 10.0 mL of ethanol. This solution was then diluted 5-fold (approximately 200 ppm) for quantification. Table 3 shows the composition of specific flavonoids in the resulting mixture.

[0213] [Table 3]

[0214] Sensory evaluation The resulting mixture was introduced into water containing 5% sucrose, and 50 ppm of the mixture was almost as sweet as 20 ppm of pure compound A01.

[0215] Example 6 - Sweetness Enhancement The test compound, (2R,3R)-3-acetoxy-5,7,3'-trihydroxy-4'-methoxyflavanone (A02), was tested as a sweetness enhancer and sweetener.

[0216] In one test, taste panelists were asked to choose between a beverage sweetened with sucrose to 9Bx and a beverage sweetened with sucrose and 2.5 ppm of test compound A02 to 7Bx. The panelists perceived the two beverages to have equivalent sweetness. This indicated that the introduction of 25 ppm of test compound A02 reduced the sucrose concentration to 2Bx.

[0217] In another test, taste panelists were asked to choose between a beverage sweetened with 200 ppm rebaudioside M and 10 ppm test compound A02 and a beverage sweetened with sucrose to 10Bx. Panelists selected the former beverage as having a sweeter taste and found that the combination of rebaudioside M and test compound A02 imparted a natural-tasting sweetness similar to that of a beverage sweetened with sucrose to 12Bx.

Claims

1. 1. Use of a flavor modifying compound to (a) enhance sweetness, (b) reduce bitterness, or (c) reduce sourness in an ingestible composition, wherein the flavor modifying compound is a compound of formula (I) or a salt thereof: 【Chemical 1】 [In the formula, R 1 is a hydrogen atom, —OH, or —O—R 1A and R 1A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 1A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 2 is a hydrogen atom, —OH, or —O—R 2A and R 2A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 2A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 3 is —OH or —O—R 3A and R 3A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 3A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 4 is a hydrogen atom, —OH, or —O—R 4A and R 4A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 4A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 5 is -OH, -O-R 5A , or —O—C(O)—R 5B and R 5A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 5A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 5B is -H, or -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 is alkyl, R 6 and R 7 are independently 1-6 Alkyl, —OH, C 1-6 Alkoxy, and —O—(C 1-6 alkylene)-O-(C 1-6 alkyl), m is 0, 1, or 2, and n is 0, 1, 2, or 3.

2. R 4 The use according to claim 1 , wherein is a hydrogen atom.

3. R 5 -O-C(O)-R 5B 3. The use according to claim 1 or 2, wherein

4. R 5B is unsubstituted C 1-6 The use according to claim 3, wherein the alkyl is alkyl.

5. R 1 and R 2 The use according to any one of claims 1 to 4, wherein is -OH.

6. R 3 The use according to any one of claims 1 to 5, wherein is -OH.

7. 7. The use according to any one of claims 1 to 6, wherein m and n are 0.

8. The flavor modifying compound is represented by formula (Ib) 【Chemistry 2】 or a salt thereof.

9. The flavor modifying compound is of formula (Id) 【Chemistry 3】 or a salt thereof.

10. 10. The use according to any one of claims 1 to 9, wherein the flavour modifying compound is present in the ingestible composition at a concentration ranging from 1 ppm to 50 ppm relative to the total weight of the ingestible composition.

11. 11. The use of any one of claims 1 to 10 to enhance the sweetness of an ingestible composition.

12. 12. The use of any one of claims 1 to 11, wherein the ingestible composition does not contain any steviol glycosides.

13. 13. The use of any one of claims 1 to 12, wherein the ingestible composition comprises a sweetener.

14. 14. The method of claim 13, wherein the sweetener is sucrose, fructose, glucose, erythritol, sucralose, xylitol, or any combination thereof.

15. 1. An ingestible composition that is not naturally occurring and that comprises a flavor-modifying compound at a concentration of 200 ppm or less, wherein the flavor-modifying compound is a compound of formula (I) or a salt thereof: 【Chemistry 4】 [In the formula, R 1 is a hydrogen atom, —OH, or —O—R 1A and R 1A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 1A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 2 is a hydrogen atom, —OH, or —O—R 2A and R 2A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 2A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 3 is —OH or —O—R 3A and R 3A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 3A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 4 is a hydrogen atom, —OH, or —O—R 4A and R 4A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 4A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 5 is -OH, -O-R 5A , or —O—C(O)—R 5B and R 5A is -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 alkyl or R 5A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having 2 to 5 sugar moieties linked by glycosidic bonds and independently selected from the group consisting of furanose and pyranose moieties; R 5B is -H, or -OH and C 1-6 C optionally substituted one or more times with a substituent selected from the group consisting of alkoxy 1-6 is alkyl, R 6 and R 7 are independently 1-6 Alkyl, —OH, C 1-6 Alkoxy, and —O—(C 1-6 alkylene)-O-(C 1-6 alkyl), m is 0, 1, or 2, and n is 0, 1, 2, or 3.

16. 16. The composition of claim 15, further comprising one or more sweeteners selected from the group consisting of sucrose, fructose, glucose, erythritol, xylitol, and any combination thereof.

17. The flavor modifying compound is represented by formula (Ib) 【Chemistry 5】 17. The composition according to claim 15 or 16, wherein the compound is:

18. The flavor modifying compound is of formula (Id) 【Chemistry 6】 17. The composition according to claim 15 or 16, wherein the compound is:

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