Flavanone derivatives and their use as sweetness enhancers

Abstract

The present disclosure generally provides a class of flavanone derivatives and their use as sweetness enhancers. In some forms, the present disclosure provides certain compositions comprising such flavanone derivatives, such as compositions comprising such flavanone derivatives and one or more other sweeteners. In some other forms, the present disclosure provides methods for reducing the caloric content of sweet products, such as sweet food or beverage products.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 62 / 896,017, filed on September 5, 2019, and European Patent Application No. 19200701.1, filed on October 1, 2019, both of which are incorporated herein by reference as if set forth in their entirety. Technical Field

[0003] The present disclosure generally provides a class of flavanone derivatives and their use as sweetness enhancers. In some forms, the present disclosure provides certain compositions comprising such flavanone derivatives, such as compositions comprising such flavanone derivatives and one or more other sweeteners. In some other forms, the present disclosure provides methods for reducing the caloric content of sweet products, such as sweet food or beverage products. Background Art

[0004] The taste system provides sensory information about the chemical composition of the outside world. Taste transduction is one of the more complex forms of chemically triggered sensation in animals. Taste signals are found throughout the animal kingdom, from simple metazoans to the most complex vertebrates. Mammals are thought to have five basic forms of taste: sweet, bitter, sour, salty, and umami.

[0005] Sweetness is the taste most often perceived when eating foods high in sugar. Mammals generally perceive sweetness as a pleasant sensation, unless in excess. Caloric sweeteners, such as sucrose and fructose, are typical examples of sweet substances. Despite the existence of a variety of non-caloric and low-calorie alternatives, these caloric sweeteners remain the primary means by which edible products induce the perception of sweetness when consumed.

[0006] Metabolic disorders and related diseases, such as obesity, diabetes, and cardiovascular disease, are major public health issues worldwide. Their prevalence is growing at an alarming rate in almost every developed country. Caloric sweeteners are a key factor in this trend, as they have been included in a variety of packaged food and beverage products to make them more palatable to consumers. In many cases, non-caloric or low-calorie alternatives can be used in place of sucrose or fructose in food and beverages. Even so, the sweetness imparted by these compounds is different from that of caloric sweeteners, and many consumers fail to consider them as suitable substitutes. Moreover, such compounds may be difficult to incorporate into certain products. In some cases, they can be used as partial substitutes for caloric sweeteners, but their presence causes many consumers to perceive unpleasant off-flavors, including astringency, bitterness, and metallic and licorice flavors. Therefore, low-calorie sweeteners face certain challenges in their adoption.

[0007] Sweet taste enhancement provides an alternative method to overcome some of the challenges of adoption faced by low-calorie sweeteners. Such compounds can be used in combination with sucrose or fructose to enhance their sweetness, thereby allowing the use of lower amounts of such caloric sweeteners in various food or beverage products. However, in addition to enhancing the perceived sweetness of the primary sweetener, such compounds still change the perceived taste of the sweetener. Therefore, many consumers find that it is more unpleasant to eat such products of sweet taste enhancement than unenhanced substitutes with higher calories. Therefore, there is a continuous need to find a class of compounds that can improve the sweetness of caloric sweeteners without changing their perceived taste in a way that impairs the pleasure experienced by consumers when eating or drinking products containing such sweeteners. Summary of the invention

[0008] The present disclosure relates to the discovery that certain compounds exhibit desirable and surprising sweetness enhancing effects when combined with a primary sweetener in an amount effective to enhance sweetness.

[0009] In a first aspect, the present disclosure provides a flavor modifying compound, which is a compound of formula (I):

[0010]

[0011] or a salt thereof, wherein:

[0012] R 1 is a hydrogen atom, -OH or -OR 1A ;

[0013] R 1A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 1A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0014] R 2 is a hydrogen atom, -OH or -OR 2A ;

[0015] R 2A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 2A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0016] R 3 Is -OH or -OR 3A ;

[0017] R 3A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 3A is a furanose moiety, a pyranose moiety or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0018] R 4 is a hydrogen atom, -OH or -OR 4A ;

[0019] R 4A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 4A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0020] R 5 It is -OH, -OR 5A or -OC(O)-R 5B ;

[0021] R 5A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 5A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0022] R 5B Yes - H or C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The substituents of the alkoxy group are substituted one or more times;

[0023] R 6 and R 7 Independently selected from C 1-6 Alkyl, -OH, C 1-6 Alkoxy and -O-(C 1-6 Alkylene)-O-(C 1-6 alkyl);

[0024] m is 0, 1, or 2; and

[0025] n is 0, 1, 2 or 3.

[0026] In a second related aspect, the present disclosure provides a flavor-improving compound, which is a compound of formula (Ia):

[0027]

[0028] or a salt thereof.

[0029] In a third related aspect, the present disclosure provides a flavor-improving compound, which is a compound of formula (Ic):

[0030]

[0031] or a salt thereof.

[0032] In a fourth aspect, the present disclosure provides use of any flavor-improving compound of the first to third aspects.

[0033] In a fifth aspect, the present disclosure provides the use of any flavor-improving compound of the first to third aspects in enhancing 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.

[0034] In a sixth aspect, the present disclosure provides use of any flavor improving compound of the first to third aspects for reducing the sour taste of an ingestible composition.

[0035] In a seventh aspect, the present disclosure provides use of any flavor improving compound of the first to third aspects for reducing the bitterness of an ingestible composition.

[0036] In an eighth aspect, the present disclosure provides the use of any flavor-improving compound 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.

[0037] In a ninth aspect, the present disclosure provides use of any flavor-improving compound of the first to third aspects in preparing an ingestible composition to reduce the sour taste of the ingestible composition.

[0038] In a tenth aspect, the present disclosure provides use of any flavor-improving compound of the first to third aspects in preparing an ingestible composition to reduce the bitterness of the ingestible composition.

[0039] In an eleventh aspect, the present disclosure provides a method for enhancing the sweetness of an ingestible composition, comprising introducing an amount (eg, an effective amount for enhancing sweetness) of any compound of the first to third aspects into the ingestible composition.

[0040] In a twelfth aspect, the present disclosure provides a method for reducing the sour taste of an ingestible composition, comprising introducing an amount (eg, an effective amount to reduce the sour taste) of any compound of the first to third aspects into the ingestible composition.

[0041] In a thirteenth aspect, the present disclosure provides a method for reducing the bitterness of an ingestible composition, comprising introducing an amount (eg, an effective amount to reduce bitterness) of any compound of the first to third aspects into the ingestible composition.

[0042] In a fourteenth aspect, the present disclosure provides a composition comprising a compound of any of the first to third aspects, wherein the compound of the first to third aspects constitutes at least 50 weight % of the composition on a dry weight basis (e.g., based on the total weight of the composition excluding the weight of any liquid carrier).

[0043] 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 of the first to third aspects constitutes at least 50 weight % of the solid composition based on the total weight of the composition.

[0044] 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 the first to third aspects in the ingestible composition does not exceed 200 ppm.

[0045] In the seventeenth aspect, the present disclosure provides an ingestible composition comprising any compound of the first to third aspects, wherein the ingestible composition comprises no more than 1000 ppm of steviol glycosides, mogrosides, or their functionalized derivatives (including chemical or enzyme functionalized derivatives). In some further embodiments, the ingestible composition comprises no more than 1000 ppm of steviol glycosides.

[0046] In an eighteenth aspect, the present disclosure provides an ingestible composition comprising a compound of any of the first to third aspects, wherein the ingestible composition comprises a caloric sweetener, such as sucrose, fructose, glucose, xylitol, erythritol, or a combination thereof.

[0047] In a nineteenth aspect, the present disclosure provides a concentrated sweetening composition comprising any compound of the first to third aspects and a sweetener.

[0048] In a twentieth aspect, the present disclosure provides a flavored product comprising any composition of the foregoing five aspects. In some embodiments, the flavored product is a beverage product, such as soda, flavored water, tea, etc. In some other embodiments, the flavored product is a food product, such as yogurt.

[0049] In a twenty-first aspect, the present disclosure provides a method of preparing a compound of the first to third aspects, comprising: providing a flavanone unsubstituted at position 3; and contacting the flavanone with an enzyme to functionalize the flavanone at position 3. In some embodiments, further functionalization is performed.

[0050] Further aspects and embodiments thereof are set forth in the following detailed description, drawings, abstract and claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] The following figures are provided to illustrate various embodiments of the compositions and methods disclosed herein. The figures are provided for illustration purposes only and are not intended to describe any preferred compositions or preferred methods, nor are they used as a source of any limitation on the scope of the claimed invention.

[0052] Figure 1 Chemical formulae representing non-limiting examples of compounds (or salts thereof) disclosed herein are shown, wherein: R 1 and R 2 R is independently a hydrogen atom, a hydroxyl group, an optionally substituted alkoxy group, a glucuronide group or a glycosyloxy group (eg, a monosaccharide, a disaccharide, a trisaccharide, etc., containing a furanose or pyranose moiety and connected to the flavanone core structure via a glycosidic bond); 3 is hydroxy, optionally substituted alkoxy, glucuronide or glycosyloxy (as described above for R 1 and R 2 R 4 is a hydrogen atom, a hydroxyl group, an optionally substituted alkoxy group, a glucuronide group or a glycosyloxy group (as described above for R 1 and R 2 R 5 is hydroxy, optionally substituted alkoxy, glucuronate, formyloxy or optionally substituted alkanoyloxy; R 6 and R 7 is an optional substituent. DETAILED DESCRIPTION

[0053] The following detailed description sets forth various aspects and embodiments provided herein. This description will be read from the perspective of a person of ordinary skill in the relevant art. Therefore, information known to these persons of ordinary skill is not necessarily included.

[0054] definition

[0055] Unless otherwise provided herein, the following terms and phrases have the meanings indicated below. The present disclosure may employ other terms and phrases not expressly defined herein. Such other terms and phrases have the meanings they have in the context of the present disclosure for those of ordinary skill in the art. In some cases, a term or phrase may be defined in the singular or in the plural. In this case, it is to be understood that any term in the singular may include its plural form, and vice versa, unless expressly indicated to the contrary.

[0056] 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 ingestible solvate, such as a hydrate.

[0057] As used herein, "C" wherein "a" and "b" are integers a To C b ” or “C a-b " refers to the number of carbon atoms in the specified group. That is, the group can contain carbon atoms from "a" to "b" (including the end values). Thus, for example, "C1 to C4 alkyl" or "C 1-4 "Alkyl" refers to all alkyl groups having 1 to 4 carbons, i.e., CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)- and (CH3)3C-.

[0058] As used herein, "halogen" or "halo" refers to any of the radiation stable atoms in column 7 of the periodic table, such as fluorine, chlorine, bromine, or iodine. In some embodiments, "halogen" or "halo" refers to fluorine or chlorine.

[0059] As used herein, "alkyl" refers to a fully saturated straight or branched hydrocarbon chain (i.e., containing no double or triple bonds). In some embodiments, an alkyl group has 1 to 20 carbon atoms (when appearing herein, a numerical range such as "1 to 20" refers to each integer in the given range; for example, "1 to 20 carbon atoms" means that the alkyl group can be composed of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms, although this definition also covers the occurrence of the term "alkyl" in which no numerical range is specified). The alkyl group can also be a medium-sized alkyl group having 1 to 9 carbon atoms. The alkyl group can also be a low-sized alkyl group having 1 to 4 carbon atoms. The alkyl group can be referred to as a "C 1-4 Alkyl" or similar designation. For example only, "C 1-4"Alkyl" means that there are 1 to 4 carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl. Typical alkyl groups include, but are by no means limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, and the like. Unless otherwise indicated, the term "alkyl" refers to a group that is not further substituted.

[0060] As used herein, "substituted alkyl" refers to an alkyl group substituted with one or more substituents independently selected from the group consisting of C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C7 carbocyclyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), halogen, cyano, hydroxy, C1-C6 alkoxy, aryloxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7 carbocyclyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclyl-oxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl-oxy (optionally substituted with halogen , C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7-carbocyclyl-C1-C6 alkoxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclyl-C1-C6-alkoxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl(C1-C6)alkoxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl(C1-C6) Alkoxy (optionally substituted with halogen, 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 halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7 carbocyclic sulfhydryl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3 to 10 membered heterocyclyl-sulfhydryl (optionally substituted with halogen, C1-C6 alkyl,C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl-thio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7-carbocyclyl-C1-C6-alkylthio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclyl-C1-C6 alkylthio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl(C1-C6)alkyl thio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl (C1-C6) alkylthio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), amino, nitro, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, acyl, cyanate, isocyanate, thiocyanate, isothiocyanate, sulfinyl, sulfonyl, and oxo (=O). ,

[0061] As used herein, "alkoxy" refers to a radical of the formula -OR, wherein R is an alkyl radical as defined above, e.g., "C 1-9 "Alkoxy" includes, but is not limited to, methoxy, ethoxy, n-propoxy, 1-methylethoxy (isopropoxy), n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, etc.

[0062] As used herein, "alkylthio" refers to a radical of the formula -SR, wherein R is an alkyl radical as defined above, e.g., "C 1-9 "Alkylthio" and the like, including but not limited to methylmercapto, ethylmercapto, n-propylmercapto, 1-methylethylmercapto (isopropylmercapto), n-butylmercapto, isobutylmercapto, sec-butylmercapto, tert-butylmercapto and the like.

[0063] As used herein, "alkenyl" refers to a straight or branched hydrocarbon chain containing one or more double bonds. In some embodiments, the alkenyl group has 2 to 20 carbon atoms, although this definition also covers the occurrence of the term "alkenyl" in which no numerical range is specified. The alkenyl group can also be a medium-sized alkenyl group having 2 to 9 carbon atoms. The alkenyl group can also be a low-sized alkenyl group having 2 to 4 carbon atoms. The alkenyl group can be referred to as a "C 2-4 "C 2-4"Alkenyl" means that there are 2 to 4 carbon atoms in the alkenyl chain, 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 in no way limited to, ethenyl, propenyl, butenyl, pentenyl and hexenyl, etc. Unless otherwise indicated, the term "alkenyl" refers to a group that is not further substituted.

[0064] 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 encompasses occurrences of the term "alkynyl" where no numerical range is specified. An alkynyl group may also be a medium-sized alkynyl group having 2 to 9 carbon atoms. An alkynyl group may also be a low-sized alkynyl group having 2 to 4 carbon atoms. An alkynyl group may be referred to as a "C 2-4 Alkynyl" or similar designation. By way of example only, "C 2-4 "Alkynyl" means that there are 2 to 4 carbon atoms in the alkynyl chain, 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 by no means limited to, ethynyl, propynyl, butynyl, pentynyl, and hexynyl, etc. Unless otherwise indicated, the term "alkynyl" refers to a group that is not further substituted.

[0065] As used herein, "heteroalkyl" refers to a straight or branched hydrocarbon chain containing one or more heteroatoms, i.e., elements other than carbon, in the backbone of the chain, including, but not limited to, nitrogen, oxygen, and sulfur. In some embodiments, a heteroalkyl group has from 1 to 20 carbon atoms, although this definition also encompasses occurrences of the term "heteroalkyl" where no numerical range is specified. A heteroalkyl group may also be a medium-sized heteroalkyl group having from 1 to 9 carbon atoms. A heteroalkyl group may also be a low-sized heteroalkyl group having from 1 to 4 carbon atoms. A heteroalkyl group may be referred to as a "C 1-4 Heteroalkyl" or similar designations. A heteroalkyl group may contain one or more heteroatoms. By way of example only, "C 1-4 "Heteroalkyl" means that there are from one to four carbon atoms in the heteroalkyl chain and one or more additional heteroatoms in the backbone of the chain. Unless otherwise indicated, the term "heteroalkyl" refers to a group that is not further substituted.

[0066] As used herein, "alkylene" refers to a fully saturated branched or straight chain diradical chemical group containing only carbon and hydrogen, which is connected to the rest of the molecule (i.e., alkanediyl) by two points of attachment. In some embodiments, alkylene has 1 to 20 carbon atoms, although this definition also encompasses occurrences of the term alkylene where no numerical range is specified. Alkylene can also be a medium-sized alkylene having 1 to 9 carbon atoms. Alkylene can also be a low-sized alkylene having 1 to 4 carbon atoms. Alkylene can be referred to as "C 1-4 Alkylene" or similar designations. For example only, "C 1-4 "Alkylene" means that there are 1 to 4 carbon atoms in the alkylene chain, i.e., the alkylene chain is selected from the group consisting of methylene, ethylene, ethane-1,1-diyl, propylene, propylene-1,1-diyl, propylene-2,2-diyl, 1-methyl-ethylene, butylene, butane-1,1-diyl, butane-2,2-diyl, 2-methyl-propylene-1,1-diyl, 1-methyl-propylene, 2-methyl-propylene, 1,1-dimethyl-ethylene, 1,2-dimethyl-ethylene and 1-ethyl-ethylene. Unless otherwise indicated, the term "alkylene" refers to a group that is not further substituted.

[0067] As used herein, "alkenylene" refers to a straight or branched diradical chemical group containing only carbon and hydrogen and containing at least one carbon-carbon double bond connected to the rest of the molecule by two points of attachment. In some embodiments, alkenylene has 2 to 20 carbon atoms, although this definition also encompasses occurrences of the term alkenylene where no numerical range is specified. Alkenylene can also be a medium-sized alkenylene having 2 to 9 carbon atoms. Alkenylene can also be a low-sized alkenylene having 2 to 4 carbon atoms. Alkenylene groups can be referred to as "C 2-4 "C 2-4The term "alkenylene" means that there are 2 to 4 carbon atoms in the alkenylene chain, i.e., the alkenylene chain is selected from the group consisting of vinylene, ethylene-1,1-diyl, propenylene, propen-1,1-diyl, prop-2-ene-1,1-diyl, 1-methylvinylene, but-1-enylidene, but-2-enylidene, buta-1,3-dienyl, butene-1,1-diyl, buta-1,3-diene-1,1-diyl, but-2-ene-1,1-diyl, buta-3-ene-1,3-diene-1,1-diyl, buta-2-ene-1,1-diyl, buta-3-ene-1,3-diene-1,3-diene-1,3-diene-1,3-diene-1,3-diene-1,3-diene-1,3-diene-1,3-diene-2,3- ... 1-ene-1,1-diyl, 1-methyl-prop-2-ene-1,1-diyl, 2-methyl-prop-2-ene-1,1-diyl, 1-ethyl-vinylene, 1,2-dimethyl-vinylene, 1-methyl-propenylene, 2-methyl-propenylene, 3-methyl-propenylene, 2-methyl-propenylene-1,1-diyl and 2,2-dimethyl-ethylene-1,1-diyl. Unless otherwise indicated, the term "alkenylene" refers to a group that is not further substituted.

[0068] As used herein, "aromatic" refers to a ring or ring system having a conjugated π electron system, and includes carbocyclic aromatic groups (e.g., phenyl) and heterocyclic aromatic groups (e.g., pyridine). The term includes monocyclic or fused-ring polycyclic (i.e., rings that share adjacent pairs of atoms) groups, provided that the entire ring system is aromatic.

[0069] 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, each ring in the system is aromatic. In some embodiments, aryl has 6 to 18 carbon atoms, although this definition also covers the occurrence of the term "aryl" where no numerical range is specified. In some embodiments, aryl has 6 to 10 carbon atoms. Aryl can be referred to as "C 6-10 Aryl", "C6-C 10 Examples 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.

[0070] As used herein, "aryloxy" and "arylthio" refer to moieties of the formula RO- and RS-, respectively, wherein R is an aryl group as defined above, e.g., "C 6-10 Aryloxy" or "C 6-10 "Arylthio" and the like, including but not limited to phenoxy and phenylthio.

[0071] As used herein, "aralkyl" or "arylalkyl" refers to an aryl group attached as a substituent through an alkylene group, for example, "C 7-14"Aralkyl" and the like, including but not limited to benzyl, 2-phenylethyl, 3-phenylpropyl, and the like. In some embodiments, the alkylene group is a lower alkylene group (i.e., C 1-4 alkylene).

[0072] As used herein, "heteroaryl" refers to an aromatic ring or ring system (i.e., two or more fused rings sharing two adjacent atoms) containing one or more heteroatoms, i.e., elements other than carbon (including but not limited to nitrogen, oxygen and sulfur) in the ring skeleton. When heteroaryl is a ring system, each ring in the system is aromatic. In some embodiments, heteroaryl has 5 to 18 ring members (i.e., the number of atoms constituting the ring skeleton, including carbon atoms and heteroatoms), although the present definition also encompasses the occurrence of the term "heteroaryl" in which no numerical range is specified. In some embodiments, heteroaryl has 5 to 10 ring members or 5 to 7 ring members. Heteroaryl may be referred to as "5 to 7-membered heteroaryl", "5 to 10-membered heteroaryl" or similar names. Examples of heteroaryl rings include, but are not limited to, furanyl, thienyl, phthalazinyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, triazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolyl, isoquinolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, indolyl, isoindolyl and benzothienyl. Unless otherwise indicated, the term "heteroaryl" refers to a group that is not further substituted.

[0073] As used herein, "heteroaralkyl" or "heteroarylalkyl" refers to a heteroaryl group attached as a substituent via an alkylene group. Examples include, but are not limited to, 2-thienylmethyl, 3-thienylmethyl, furanylmethyl, thienylethyl, pyrrolylalkyl, pyridylalkyl, isoxazolylalkyl, and imidazolylalkyl. In some cases, the alkylene group is a lower alkylene group (i.e., C 1-4 alkylene).

[0074] As used herein, "carbocyclyl" refers to a non-aromatic ring or ring system that contains only carbon atoms in the ring system backbone. When a carbocyclyl is a ring system, two or more rings may be fused, bridged, or spiro-connected. A carbocyclyl may have any degree of saturation, provided that at least one ring in the ring system is not aromatic. Thus, carbocyclyl includes cycloalkyl, cycloalkenyl, and cycloalkynyl. In some embodiments, a carbocyclyl has 3 to 20 carbon atoms, although this definition also encompasses occurrences of the term "carbocyclyl" in which no numerical range is specified. A carbocyclyl may also be a medium-sized carbocyclyl having 3 to 10 carbon atoms. A carbocyclyl may also be a carbocyclyl having 3 to 6 carbon atoms. A carbocyclic group may be referred to as a "C 3-6Examples of carbocyclyl rings include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, 2,3-dihydroindane, bicyclo[2.2.2]octyl, adamantyl, and spiro[4.4]nonyl. Unless otherwise indicated, the term "carbocyclyl" refers to a group that is not further substituted.

[0075] As used herein, "(carbocyclyl)alkyl" refers to a carbocyclyl group attached as a substituent via an alkylene group, for example, "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.

[0076] As used herein, "cycloalkyl" refers to a fully saturated carbocyclyl ring or ring system according to any of the embodiments described above for carbocyclyl. Examples include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0077] As used herein, "cycloalkenyl" refers to a carbocyclyl ring or ring system having at least one double bond, wherein no ring in the ring system is aromatic, and according to any of the embodiments described above for carbocyclyl. An example is cyclohexenyl.

[0078] As used herein, "heterocyclic radical" refers to a non-aromatic ring or ring system containing at least one heteroatom in the ring skeleton. The heterocyclic radical can be connected together in a fused, bridged or spirally connected manner. The heterocyclic radical can have any degree of saturation, provided that at least one ring in the ring system is not aromatic. The heteroatom can be present in the non-aromatic or aromatic ring of the ring system. In some embodiments, the heterocyclic radical has 3 to 20 ring members (i.e., the number of atoms constituting the ring skeleton, including carbon atoms and heteroatoms), although the definition also covers the occurrence of the term "heterocyclic radical" in which the numerical range is not specified. The heterocyclic radical can also be a medium-sized heterocyclic radical with 3 to 10 ring members. The heterocyclic radical can also be a heterocyclic radical with 3 to 6 ring members. The heterocyclic radical can be referred to as a "3 to 6-membered heterocyclic radical" or similar names. In preferred six-membered monocyclic heterocyclyls, the heteroatoms are selected from one to up to three of O, N or S, and in preferred five-membered monocyclic heterocyclyls, the heteroatoms are selected from one or two heteroatoms selected from O, N or S. Examples of heterocyclyl rings include, but are not limited to, azepinyl, acridinyl, carbazolyl, cinnolinyl, dioxolanyl, imidazolinyl, imidazolidinyl, morpholinyl, oxiranyl, oxepanyl, thiepanyl, piperidinyl, piperazinyl, dioxopiperazinyl, pyrrolidonyl, pyrrolidionyl, 4-piperidonyl, pyrazolinyl, pyrazolidinyl, 1,3-dioxinyl, 1,3-dioxinyl, 1,4-dioxinyl, 1,4-dioxinyl, 1,3-oxathian ... yl), 1,4-oxathiinyl, 1,4-oxathiinyl, 2H-1,2-oxazinyl, trioxanyl, hexahydro-1,3,5-triazinyl, 1,3-dioxolyl, 1,3-dioxolanyl, 1,3-dithiolyl, 1,3-dithiolanyl, isoxazoline 1,3-oxathiolanyl, indolinyl, isoindolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydro-1,4-thiazinyl, thiamorpholinyl, dihydrobenzofuranyl, benzimidazolidinyl and tetrahydroquinoline.

[0079] As used herein, "(heterocyclyl)alkyl" refers to a heterocyclyl group attached via an alkylene group as a substituent. Examples include, but are not limited to, imidazolinylmethyl and indolinylethyl.

[0080] "Acyl" refers to -C(=O)R, where R is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5 to 10 membered heteroaryl and 3 to 10 membered heterocyclyl are as defined herein. Non-limiting examples include formyl, acetyl, propionyl, benzoyl and acryloyl.

[0081] "O-carboxyl" refers to a "-OC(=O)R" group, wherein R is selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0082] "C-carboxyl" refers to a "-C(=O)OR" group, wherein R is selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl are as defined herein. Non-limiting examples include carboxyl (ie, -C(=O)OH).

[0083] A "cyano" group refers to a "-CN" group.

[0084] A "cyanate" group refers to a "-OCN" group.

[0085] An "isocyanate" group refers to a "-NCO" group.

[0086] A "thiocyanate" group refers to a "-SCN" group.

[0087] An "isothiocyanate" group refers to a "-NCS" group.

[0088] "Sulfinyl" refers to a "-S(=O)R" group, where R is selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0089] "Sulfonyl" refers to a "-SO2R" group where R is selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0090] "S-sulfonamide" refers to "-SO2NR A R B " group, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0091] "N-sulfonylamino" refers to "-N(R A )SO2R B ”, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0092] "O-carbamoyl" refers to "-OC(=O)NR A R B " group, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0093] "N-carbamoyl" refers to "-N(R A )C(=O)OR B " group, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0094] "O-thiocarbamoyl" refers to "-OC(=S)NR A R B " group, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0095] "N-thiocarbamoyl" refers to "-N(R A )C(=S)OR B " group, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0096] "C-amido" refers to "-C(=O)NR A R B " group, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0097] "N-amido" refers to "-N(R A )C(=O)R B " group, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein.

[0098] "Amino" refers to "-NR A R B " group, where R A and R B are each independently selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-7 Carbocyclic group, C 6-10 Aryl, 5- to 10-membered heteroaryl and 3- to 10-membered heterocyclyl are as defined herein. Non-limiting examples include free amino (ie, -NH2).

[0099] "Aminoalkyl" refers to an amino group attached through an alkylene group.

[0100] "Alkoxyalkyl" refers to an alkoxy group attached through an alkylene group, for example, "C 2-8 "Alkoxyalkyl" and the like.

[0101] As used herein, a "glucosyl moiety" is a monovalent moiety in which one of the hydroxyl groups of a glucose is replaced by a bond, functional group, or moiety to another atom. Unless otherwise indicated, a glucose can have any suitable stereochemistry. Thus, the term includes moieties having a D stereochemistry as well as moieties having an L stereochemistry. In addition, the term includes moieties having an α stereochemistry as well as moieties having a β stereochemistry. The carbon atoms of the glucosyl moiety follow conventional numbering, as shown below. The figure shows β-D glucose, but applies in a similar manner to glucosyl moieties having α and / or L stereochemistry:

[0102]

[0103] 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, functional group, or moiety to another atom. Unless otherwise indicated, glucuronic acid can have any suitable stereochemistry. Thus, the term includes moieties having D stereochemistry as well as moieties having L stereochemistry. In addition, the term includes moieties having α stereochemistry as well as moieties having β stereochemistry. The carbon atoms of the glucuronyl moiety follow conventional numbering, as shown below. The figure shows β-D glucuronic acid, but applies in a similar manner to glucuronyl moieties having α and / or L stereochemistry:

[0104]

[0105] The term "C 1-6 An "alkyl glucuronyl ester moiety" means a glucuronyl moiety (as defined in this paragraph) in which the carboxylic acid group of the glucuronic acid has a C 1-6 In any of the following embodiments, C1-6 The alkyl portion can have any suitable value, such as methyl, ethyl, isopropyl, propyl, butyl, pentyl, etc. In some embodiments, C 1-6 In some other embodiments, the alkyl moiety is methyl. 1-6 The alkyl portion is ethyl.

[0106] As used herein, a substituted group is derived from an unsubstituted parent group in which one or more hydrogen atoms have been exchanged with another atom or group. Unless otherwise specified, when a group is considered to be "substituted by...", it means that the group is substituted with one or more substituents independently selected from C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 heteroalkyl, C3-C7 carbocyclyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7-carbocyclyl-C1-C6-alkyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3 to 10 membered heterocyclyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), , C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclic-C1-C6-alkyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl(C1-C6)alkyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl(C1-C6)alkyl (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), halogen, cyano, hydroxy, C1-C6 alkoxy, C1-C6 alkoxy(C1-C6)alkyl (i.e. ether), aryloxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7 carbocyclic group (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclyloxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryloxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7-carbocyclyl-C1-C6 alkoxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclyl-C1-C6-alkoxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy,C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl(C1-C6)alkoxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl(C1-C6)alkoxy (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), sulfhydryl (thiol), halo(C1-C6)alkyl (e.g. -CF3), halo(C1-C6)alkoxy (e.g. -OCF3), C1-C6 alkylthio C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C3-C7 carbocyclic thio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclyl-thio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 5- to 10-membered heteroaryl-thio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), C1-C6 alkylthio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), 3- to 10-membered heterocyclyl-C1-C6 alkylthio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), aryl(C1-C6)alkylthio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), , 5- to 10-membered heteroaryl(C1-C6)alkylthio (optionally substituted with halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl and C1-C6 haloalkoxy), amino, amino(C1-C6)alkyl, nitro, O-carbamoyl, N-carbamoyl, O-thiocarbamoyl, N-thiocarbamoyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, O-carboxy, acyl, cyanate, isocyanate, thiocyanate, isothiocyanate, sulfinyl, sulfonyl, and oxo (═O). Where a group is described as “optionally substituted with”, the group may be substituted with the substituents listed above. ,

[0107] It should be understood that certain radical naming conventions may include monoradicals or diradicals, depending on the context. For example, when a substituent requires two points of attachment to the rest of the molecule, it is understood that the substituent is a diradical. For example, a substituent that is identified as an alkyl group that requires two points of attachment includes diradicals, such as -CH2-, -CH2CH2-, -CH2CH(CH3)CH2-, etc. Other radical naming conventions clearly indicate that the radical is a diradical, such as "alkylene" or "alkenylene".

[0108] Where a substituent is described as diradical (i.e., having two points of attachment to the rest of the molecule), it is understood that the substituent may be attached in any orientation unless otherwise indicated. Thus, for example, a substituent represented by -AE- or Substituents of include those oriented such that A is attached at the left-most point of attachment in the molecule as well as those where A is attached at the right-most point of attachment in the molecule.

[0109] As used herein, "sweetener," "sweet flavoring," "sweet flavor entity," or "sweet compound" refers to a compound or an ingestibly acceptable salt thereof that induces a detectable sweet taste in a subject, such as a compound that activates T1R2 / T1R3 receptors in vitro.

[0110] 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" encompasses a single substituent as well as two or more substituents, and so forth.

[0111] As used herein, "for example," "such as," "such as," or "including" are intended to introduce examples that further illustrate a more general subject matter. Unless otherwise expressly noted, such examples are provided merely to aid in understanding the embodiments shown in the present disclosure and are not meant to be limiting in any way. These phrases also do not indicate any kind of preference for the disclosed embodiments.

[0112] As used herein, "include," "comprising," "containing," and "comprised of" refer to an open group, meaning that the group may include other members in addition to those explicitly stated. For example, the phrase "comprising A" means that A must be present, but other members may also be present. The terms "including," "having," and "composed of" and their grammatical variants have the same meaning. In contrast, "consist of" or "composed of" or "composed of" refer to a closed group. For example, the phrase "consisting of A" means that only A is present.

[0113] As used herein, "optionally" means that the subsequently described event may or may not occur. In some embodiments, the optional event does not occur. In some other embodiments, the optional event does occur one or more times.

[0114] As used herein, "or" is to be given its broadest reasonable interpretation and is not limited to an "either / or" construction. Thus, the phrase "comprising A or B" means that A may be present and B may not be present, or B may be present and A may not be present, or both A and B may be present. Furthermore, for example, if A defines a class that may have multiple members (e.g., A1 and A2), then one or more members of the class may be present at the same time.

[0115] As used herein, the term "flavor improving compound" refers to a compound of formula (I) or a salt thereof, or any embodiment thereof as described herein. For example, in some cases, the term "flavor improving compound" refers to a compound of formula (Ia). In some cases, the term "flavor improving compound" refers to a compound of formula (Ib). In some cases, the term "flavor improving compound" refers to a compound of formula (Ic). In some cases, the term "flavor improving compound" refers to a compound of formula (Id).

[0116] As used herein, certain monovalent or polyvalent 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", or 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".

[0117] 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 ethyl groups.

[0118] Chemical structures are often displayed using a "skeleton" format, so that the carbon atoms are not explicitly shown and hydrogen atoms attached to the carbon atoms are omitted entirely. For example, the structure represents butane (i.e., n-butane). In addition, aromatic groups such as benzene are represented by showing a contributing resonance structure. For example, the structure Represents toluene.

[0119] Positions on the flavanone ring may be indicated by numbers, such as "position 2," "position 3," and the like. These terms refer to a specific position on the flavanone fused ring structure, even though further substitution of the fused ring structure may result in a different numbering of the position. Thus, for example, the position of a carbonyl substitution is referred to as occurring at "position 4," regardless of whether, in some embodiments, the addition of further substituents would result in it occurring at a position other than position 4 of the fused ring structure. Similarly, the position of a phenyl substituent substituted on the fused ring structure is referred to as occurring at "position 2," regardless of whether, in some embodiments, the addition of further substituents would result in it occurring at a position other than position 2 of the fused ring structure.

[0120] Other terms are defined in other parts of this specification even if not included in this section.

[0121] Flavanone derivatives

[0122] In a first aspect, the present disclosure provides a flavor improving compound, which is a compound of formula (I):

[0123]

[0124] or a salt thereof, wherein:

[0125] R 1 is a hydrogen atom, -OH or -OR 1A ;

[0126] R 1A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 1A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0127] R 2 is a hydrogen atom, -OH or -OR 2A ;

[0128] R 2A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 2A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0129] R 3 Is -OH or -OR 3A ;

[0130] R 3A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 3A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0131] R 4 is a hydrogen atom, -OH or -OR 4A ;

[0132] R 4A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 4A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0133] R 5 It is -OH, -OR 5A or -OC(O)-R 5B ;

[0134] R 5A It is C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The alkoxy substituents are substituted one or more times; or R 5A is a glucuronyl moiety, a furanose moiety, a pyranose moiety, or an oligosaccharide moiety having two to five sugar moieties linked by glycosidic bonds and independently selected from furanose moieties and pyranose moieties;

[0135] R 5B Yes - H or C 1-6 Alkyl, which is optionally selected from -OH and C 1-6 The substituents of the alkoxy group are substituted one or more times;

[0136] R 6 and R 7 Independently selected from C 1-6 Alkyl, -OH, C 1-6 Alkoxy and -O-(C 1-6 Alkylene)-O-(C 1-6 alkyl);

[0137] m is 0, 1, or 2; and

[0138] n is 0, 1, 2 or 3.

[0139] Various embodiments of the aforementioned aspects are also considered to be part of the present disclosure. These embodiments are described below and throughout the rest of the detailed description.

[0140] In some embodiments of the first form, R 1 is a hydrogen atom. In some other embodiments, R 1 In some other embodiments, R 1 Yes-OR 1A In some additional such embodiments of any of the foregoing embodiments, R 1A It is C 1-6 In some other embodiments, R 1A is unsubstituted C 1-6 In some embodiments, R 1A In some other embodiments, R 1A is a glucuronic acid moiety. In some other embodiments, R 1A is a furanose moiety or a pyranose moiety, such as a glucosidyl moiety. 1A is an oligosaccharide moiety, as described above, such as a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety or a pentaglucosidyl moiety.

[0141] In some embodiments of any of the preceding embodiments, R 2 is a hydrogen atom. In some other embodiments, R 2 is -OH. In some other embodiments of any of the foregoing embodiments, R 2 Yes-OR 2A In some further such embodiments, R 2A It is C 1-6 In some other embodiments, R 2A is unsubstituted C 1-6 In some embodiments, R 2A In some other embodiments, R 2A is a glucuronic acid moiety. In some other embodiments, R 2A is a furanose moiety or a pyranose moiety, such as a glucosidyl moiety. In some other embodiments, R 2A is an oligosaccharide moiety, as described above, such as a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety or a pentaglucosidyl moiety.

[0142] In some embodiments of any of the preceding embodiments, R3 is -OH. In some other embodiments of any of the foregoing embodiments, R 3 Yes-OR 3A In some further such embodiments, R 3A It is C 1-6 In some other embodiments, R 3A is unsubstituted C 1-6 In some embodiments, R 3A In some other embodiments, R 3A is a glucuronic acid moiety. In some other embodiments, R 3A is a furanose moiety or a pyranose moiety, such as a glucosidyl moiety. In some other embodiments, R 3A is an oligosaccharide moiety, as described above, such as a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety or a pentaglucosidyl moiety.

[0143] In some embodiments of any of the preceding embodiments, R 4 is a hydrogen atom. In some other embodiments of any of the foregoing embodiments, R 4 is -OH. In some other embodiments of any of the foregoing embodiments, R 4 Yes-OR 4A In some further such embodiments, R 4A It is C 1-6 In some other embodiments, R 4A is unsubstituted C 1-6 In some embodiments, R 4A In some other embodiments, R 4A is a glucuronic acid moiety. In some other embodiments, R 4A is a furanose moiety or a pyranose moiety, such as a glucosidyl moiety. In some other embodiments, R 4A is an oligosaccharide moiety, as described above, such as a diglucosidyl moiety, a triglucosidyl moiety, a tetraglucosidyl moiety or a pentaglucosidyl moiety.

[0144] In some embodiments of any of the preceding embodiments, R 5 is -OH. In some other embodiments of any of the foregoing embodiments, R 5 Yes-OR 5A In some additional such embodiments, R 5A It is C 1-6In some other embodiments, R 5A is unsubstituted C 1-6 In some embodiments, R 5A In some other embodiments, R 5A is a glucuronic acid moiety. In some other embodiments, R 5A is a furanose moiety or a pyranose moiety, such as a glucosidyl moiety. In some other embodiments, R 5A is an oligosaccharide moiety, such as described above, e.g., a diglucoside moiety, a triglucoside moiety, a tetraglucoside moiety, or a pentaglucoside moiety. In some other embodiments of any of the foregoing embodiments, R 5 Yes-OC(O)-R 5B In some further such embodiments, R 5B It is C 1-6 In some other embodiments, R 5B is unsubstituted C 1-6 In some embodiments, R 5B In some other such embodiments, R 5B It's a hydrogen atom.

[0145] The variables m and n can have any suitable values ​​within the above definitions. In some embodiments of any of the foregoing embodiments, m is 0. In some other embodiments of any of the foregoing embodiments, m is 1. In some embodiments of any of the foregoing embodiments, n is 0. In some other embodiments of any of the foregoing embodiments, n is 1. Note that R 6 refers to non-hydrogen substituents that are optionally present at two positions (which represent positions 6 and 8 according to the traditional numbering of flavanones) of the phenyl portion of the bicyclic system. Thus, when m is 0, the substituents at these two positions are both hydrogen atoms. When m is 1, then a non-hydrogen substituent is present at one of the two positions, selected from R 6 The variables listed in the definition. When m is 2, there is a non-hydrogen substituent at both positions. In a similar manner, R 7 refers to non-hydrogen substituents that are optionally present at three positions on the benzene ring attached to the 2-position of the bicyclic ring (according to the conventional position numbering of flavanones). Therefore, when n is 0, these three positions (i.e., except R 3 and R 4The substituents at the three positions other than the position occupied by 1 are hydrogen atoms. When n is 1, there is a non-hydrogen substituent at one of the three available positions. When n is 2, there are non-hydrogen substituents at two of the three available positions. When n is 3, there is a non-hydrogen substituent at each of the three available positions.

[0146] In some embodiments of any of the preceding embodiments, R 1 and R 2 Yes -OH, 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 Yes -H.

[0147] In a related aspect, the present disclosure provides a flavor-improving compound, which is a compound of formula (Ia):

[0148]

[0149] 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 the 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., a purity of 95% or more, or 97% or more, 98% or more, or 99% or more, or 99.5% or more, or 99.7% or more, or 99.9% or more.

[0150] In some further embodiments thereof, the flavor improving compound is a compound of formula (Ib)

[0151]

[0152] or a salt thereof.

[0153] In a related form, the present disclosure provides a flavor-improving compound, which is a compound of formula (Ic)

[0154]

[0155] 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 the 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., a purity of 95% or more, or 97% or more, 98% or more, or 99% or more, or 99.5% or more, or 99.7% or more, or 99.9% or more.

[0156] In some further embodiments thereof, the flavor improving compound is a compound of formula (Id)

[0157]

[0158] or a salt thereof.

[0159] Where the compounds disclosed herein possess at least one chiral center, they may exist as individual enantiomers and diastereomers or as mixtures of such isomers.In some embodiments related to the second aspect, the sweet taste enhancing compound has substantial enantiomeric purity.

[0160] For example, in some embodiments, the composition comprising a compound of formula (Ia) or a salt thereof, based on the total weight of the compound 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)], the (2R, 3R) enantiomer accounts for 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 amount of the compound present in the composition. In some other embodiments, the composition comprising a compound of formula (Ia) or a salt thereof, based on the total weight of the compound in the composition, the (2R, 3S) enantiomer accounts for 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 amount of the compound present in the composition. In some other embodiments, the composition comprising a compound of formula (Ia) or a salt thereof, based on the total weight of the compound in the composition, the (2S, 3R) enantiomer accounts for 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 amount of the compound present in the composition. In some other embodiments, the composition comprising a compound of formula (Ia) or a salt thereof, based on the total weight of the compound in the composition, the (2S, 3S) enantiomer accounts for 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 amount of the compound present in the composition.

[0161] In some other embodiments of any embodiment of the preceding paragraph, in a composition comprising a compound of formula (Ia) or a salt thereof, the (2R, 3R) enantiomer accounts for no more than 50% by weight, or no more than 40% by weight, or no more than 30% by weight, or no more than 20% by weight, or no more than 10% by weight, or no more than 5% by weight, or no more than 3% by weight, or no more than 1% by weight of the amount of the compound present in the composition, based on the total weight of the compound in the composition. In some other embodiments of any embodiment of the preceding paragraph, in a composition comprising a compound of formula (Ia) or a salt thereof, the (2R, 3S) enantiomer accounts for no more than 50% by weight, or no more than 40% by weight, or no more than 30% by weight, or no more than 20% by weight, or no more than 10% by weight, or no more than 5% by weight, or no more than 3% by weight, or no more than 1% by weight of the amount of the compound present in the composition, based on the total weight of the compound in the composition. In some other embodiments of any embodiment of the preceding paragraph, in a composition comprising a compound of formula (Ia) or a salt thereof, the (2S, 3R) enantiomer accounts for no more than 50% by weight, or no more than 40% by weight, or no more than 30% by weight, or no more than 20% by weight, or no more than 10% by weight, or no more than 5% by weight, or no more than 3% by weight, or no more than 1% by weight of the amount of the compound present in the composition, based on the total weight of the compound in the composition. In some other embodiments of any embodiment of the preceding paragraph, in a composition comprising a compound of formula (Ia) or a salt thereof, the (2S, 3S) enantiomer accounts for no more than 50% by weight, or no more than 40% by weight, or no more than 30% by weight, or no more than 20% by weight, or no more than 10% by weight, or no more than 5% by weight, or no more than 3% by weight, or no more than 1% by weight of the amount of the compound present in the composition, based on the total weight of the compound in the composition.

[0162] For example, in some embodiments, the composition comprising the compound of formula (Ic) or its salt, based on the total weight of the compound 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)], the (2R, 3R) enantiomer accounts for 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 amount of the compound present in the composition. In some other embodiments, the composition comprising the compound of formula (Ic) or its salt, based on the total weight of the compound in the composition, the (2R, 3S) enantiomer accounts for 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 amount of the compound present in the composition. In some other embodiments, the composition comprising the compound of formula (Ic) or its salt, based on the total weight of the compound in the composition, the (2S, 3R) enantiomer accounts for 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. In some other embodiments, the composition comprising the compound of formula (Ic) or its salt, based on the total weight of the compound in the composition, the (2S, 3S) enantiomer accounts for 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.

[0163] In some other embodiments of any embodiment of the previous paragraph, in a composition comprising a compound of formula (Ic) or a salt thereof, the (2R, 3R) enantiomer accounts for no more than 50% by weight, or no more than 40% by weight, or no more than 30% by weight, or no more than 20% by weight, or no more than 10% by weight, or no more than 5% by weight, or no more than 3% by weight, or no more than 1% by weight of the amount of the compound present in the composition, based on the total weight of the compound in the composition. In some other embodiments of any embodiment of the previous paragraph, in a composition comprising a compound of formula (Ic) or a salt thereof, the (2R, 3S) enantiomer accounts for no more than 50% by weight, or no more than 40% by weight, or no more than 30% by weight, or no more than 20% by weight, or no more than 10% by weight, or no more than 5% by weight, or no more than 3% by weight, or no more than 1% by weight of the amount of the compound present in the composition, based on the total weight of the compound in the composition. In some other embodiments of any embodiment of the preceding paragraph, in a composition comprising a compound of formula (Ic) or a salt thereof, the (2S, 3R) enantiomer accounts for no more than 50% by weight, or no more than 40% by weight, or no more than 30% by weight, or no more than 20% by weight, or no more than 10% by weight, or no more than 5% by weight, or no more than 3% by weight, or no more than 1% by weight of the amount of the compound present in the composition, based on the total weight of the compound in the composition. In some other embodiments of any embodiment of the preceding paragraph, in a composition comprising a compound of formula (Ic) or a salt thereof, the (2S, 3S) enantiomer accounts for no more than 50% by weight, or no more than 40% by weight, or no more than 30% by weight, or no more than 20% by weight, or no more than 10% by weight, or no more than 5% by weight, or no more than 3% by weight, or no more than 1% by weight of the amount of the compound present in the composition, based on the total weight of the compound in the composition.

[0164] The separation of each isomer or the selective synthesis of each isomer is completed by applying various methods well known to those skilled in the art. Unless otherwise stated (for example, in the case of clearly showing the stereochemistry of the chiral center), all such isomers and mixtures thereof are included in the scope of the compounds disclosed herein. In addition, the compounds disclosed herein may exist in one or more crystalline or amorphous forms. Unless otherwise stated, all these forms are included in the scope of the compounds disclosed herein, including any polymorphic form. In addition, some compounds disclosed herein can form solvates with water (i.e., hydrates) or common organic solvents. Unless otherwise stated, these solvates are included in the scope of the compounds disclosed herein.

[0165] Those skilled in the art will recognize that some of the structures described herein may be resonance forms or tautomers of compounds that can be reasonably represented by other chemical structures, even kinetically; the skilled artisan recognizes that such structures may represent only a small fraction of such compound samples. Such compounds are considered to be within the scope of the structures shown, even though such resonance forms or tautomers are not shown herein.

[0166] Isotopes may be present in the compound. Each chemical element represented by a compound structure may include any isotope of the element. For example, in a compound structure, a hydrogen atom may be explicitly disclosed or understood to be present in the compound. Any position where a hydrogen atom may be present in the compound may be any isotope of hydrogen, including but not limited to hydrogen-1 (protium) and hydrogen-2 (deuterium). Therefore, the compounds mentioned herein encompass all potential isotopic forms unless the context clearly indicates otherwise.

[0167] In some embodiments, the compounds disclosed herein are capable of forming acidic or basic salts due to the presence of amino or carboxyl groups or groups similar thereto. Physiologically acceptable acid addition salts can be formed with inorganic acids 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 can be formed with inorganic bases and organic bases. Inorganic bases from which salts can be derived include, for example, bases containing sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like; particularly preferred are ammonium, potassium, sodium, calcium, and magnesium salts. In some embodiments, treatment of the compounds disclosed herein with an inorganic base causes the compound to lose unstable hydrogen, thereby obtaining a compound containing 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, secondary and tertiary amines, substituted amines, including naturally occurring substituted amines, cyclic amines, basic ion exchange resins and the like, in particular isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine and ethanolamine.

[0168] Uses and methods

[0169] In another form, the present disclosure provides the use of any flavor-improving compound of the aforementioned form (including any embodiment or combination of its embodiments as described above). In certain related forms, the present disclosure provides the use of any flavor-improving compound of the aforementioned form (including any embodiment or combination of its embodiments as described above) for enhancing the sweetness of an ingestible composition. In some embodiments thereof, the ingestible composition comprises a sweetener, such as a caloric sweetener. In certain other related forms, the present disclosure provides the use of any flavor-improving compound of the aforementioned form (including any embodiment or combination of its embodiments as described above) for reducing the sour taste of an ingestible composition. In another related form, the present disclosure provides the use of any flavor-improving compound of the aforementioned form (including any embodiment or combination of its embodiments as described above) for reducing the bitterness of an ingestible composition. In certain other related forms, the present disclosure provides the use of any flavor-improving compound of the aforementioned form (including any embodiment or combination of its embodiments as described above) in preparing an ingestible composition to enhance the sweetness of an 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 flavor-improving compound of the foregoing aspects (including any embodiment or combination of its embodiments as described above) in preparing an ingestible composition to reduce the sour taste of the ingestible composition. In another related aspect, the present disclosure provides the use of any flavor-improving compound of the foregoing aspects (including any embodiment or combination of its embodiments as described above) in preparing an ingestible composition to reduce the bitter taste of the ingestible composition.

[0170] The present disclosure also provides a method corresponding to each of the above-mentioned uses. Therefore, in some related forms, the present disclosure provides a method for enhancing the sweetness of an ingestible composition, including introducing a certain amount (e.g., an effective amount to enhance sweetness) of any flavor-improving compound of the aforementioned form (including any embodiment or a combination of its embodiments as described above) into the ingestible composition. In some other related forms, the present disclosure provides a method for reducing the sourness of an ingestible composition, including introducing a certain amount (e.g., an effective amount to reduce sourness) of any flavor-improving compound of the aforementioned form (including any embodiment or a combination of its embodiments as described above) into the ingestible composition. In some other related forms, the present disclosure provides a method for reducing the bitterness of an ingestible composition, including introducing a certain amount (e.g., an effective amount to reduce bitterness) of any flavor-improving compound of the aforementioned form (including any embodiment or a combination of its embodiments as described above) into the ingestible composition.

[0171] Foregoing purposes and methods generally relate to the use of flavor improvement compounds in compositions containing one or more additional ingredients. For example, in at least one form, the present disclosure provides a composition comprising any flavor improvement compound of the aforementioned form (including any embodiment as described above or a combination of its embodiments), wherein on a dry weight basis (e.g., based on the total weight of the composition excluding any liquid carrier weight), the flavor improvement compound constitutes at least 50 weight % of the composition. In a related form, the present disclosure provides a solid composition comprising any flavor improvement compound of the aforementioned form (including any embodiment as described above or a combination of its embodiments), wherein based on the total weight of the composition, the flavor improvement compound constitutes at least 50 weight % of the solid composition. In another related form, the present disclosure provides an ingestible composition comprising any flavor improvement compound of the aforementioned form (including any embodiment as described above or a combination of its embodiments), wherein the concentration of the flavor improvement compound in the ingestible composition is no more than 200ppm. In another related form, the present disclosure provides an ingestible composition comprising any flavor-improving compound of the foregoing form (including any embodiment or combination of its embodiments as described above), wherein the ingestible composition comprises no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppmppm, or no more than 100ppm, or no more than 50ppm of steviol glycosides (including rebaudioside A). In another related form, the present disclosure provides an ingestible composition comprising any flavor-improving compound of the foregoing form (including any embodiment or combination of its embodiments as described above), wherein the ingestible composition contains a caloric sweetener, such as sucrose, fructose, xylitol, erythritol, or a combination thereof. In another related form, the present disclosure provides a concentrated sweetening composition comprising any flavor-improving compound of the foregoing form (including any embodiment or combination of its embodiments as described above), and a sweetener.

[0172] In certain embodiments of any of the configurations and embodiments described herein involving ingestible compositions, the ingestible composition is a non-naturally occurring product, such as a composition specifically manufactured for the production of a flavored product, such as a food or beverage product.

[0173] In general, the compounds disclosed and described herein can be provided alone or in combination in the form of a composition, such as an ingestible composition. In one embodiment, by combining one or more compounds disclosed and described herein with one or more sweeteners in a sweetener composition, the compounds disclosed and described herein can impart a time profile or flavor profile that is more similar to sugar to the sweetener composition, either alone or in combination. In another embodiment, the compounds disclosed and described herein can increase or enhance the sweetness of the composition, either alone or in combination, by contacting the composition with the compounds disclosed and described herein to form an improved composition.

[0174] In some specific embodiments, the ingestible composition comprises sucrose and flavor improving compounds. In some such embodiments, the introduction of flavor improving compounds allows people to use less sucrose (e.g., reduce by more than 10%, reduce by more than 20%, reduce by more than 30%, reduce by more than 40%, reduce by more than 50%, reduce by more than 60%, or reduce by more than 70%), and still reach the sweetness characteristic level of comparable products using more sucrose. In some embodiments, the concentration of flavor improving compounds is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm. This ingestible composition can be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as soda water, etc. Sucrose may be introduced in any suitable form such as natural syrup (sucrose syrup) and the like.

[0175] In some specific embodiments, the ingestible composition comprises fructose and flavor improving compound.In some such embodiments, the introduction of flavor improving compound allows people to use less fructose (e.g., reduce by more than 10%, reduce by more than 20%, reduce by more than 30%, reduce by more than 40%, reduce by more than 50%, reduce by more than 60%, or reduce by more than 70%), and still reach the sweetness characteristic level of comparable products using more fructose.In some embodiments, the concentration of flavor improving compound is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm.In some embodiments, the ingestible composition is a food product, such as any one of those specifically listed below.In other embodiments, the ingestible composition is a beverage product, such as soda water, etc. Fructose may be provided in any suitable form such as natural syrup, high fructose corn syrup, and the like.

[0176] In certain specific embodiments, the ingestible composition comprises high fructose corn syrup and flavor improving compounds. In some such embodiments, the introduction of flavor improving compounds allows people to use less high fructose corn syrup (e.g., reduce by more than 10%, reduce by more than 20%, reduce by more than 30%, reduce by more than 40%, reduce by more than 50%, reduce by more than 60%, or reduce by more than 70%), and still reach the sweetness characteristic level of comparable products using more high fructose corn syrup. In some embodiments, the concentration of the flavor improving compound does not exceed 1000ppm, or does not exceed 900ppm, or does not exceed 800ppm, or does not exceed 700ppm, or does not exceed 600ppm, or does not exceed 500ppm, or does not exceed 400ppm, or does not exceed 300ppm, or does not exceed 200ppm, or does not exceed 100ppm, or does not exceed 50ppm, or does not exceed 25ppm, or does not exceed 10ppm. In some embodiments, the ingestible composition is a food product, such as any of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as soda water, etc.

[0177] In certain specific embodiments, the ingestible composition comprises glucose (e.g., D-glucose in α or β form, or a combination thereof) and a flavor improving compound. In some such embodiments, the introduction of flavor improving compounds allows people to use less glucose (e.g., reduce by more than 10%, reduce by more than 20%, reduce by more than 30%, reduce by more than 40%, reduce by more than 50%, reduce by more than 60%, or reduce by more than 70%), and still reach the sweetness characteristic level of comparable products using more glucose. In some embodiments, the concentration of the flavor improving compound is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm. This ingestible composition can be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as soda, etc. The glucose may be introduced in any suitable form, such as a natural syrup, etc.

[0178] In certain specific embodiments, the ingestible composition comprises sucralose and a flavor improving compound. In some such embodiments, the introduction of the flavor improving compound allows people to use less sucralose (e.g., a reduction of more than 10%, a reduction of more than 20%, a reduction of more than 30%, a reduction of more than 40%, a reduction of more than 50%, a reduction of more than 60%, or a reduction of more than 70%), and still achieves the level of sweetness characteristics of comparable products using more sucralose. In some embodiments, the concentration of the flavor improving compound does not exceed 1000ppm, or does not exceed 900ppm, or does not exceed 800ppm, or does not exceed 700ppm, or does not exceed 600ppm, or does not exceed 500ppm, or does not exceed 400ppm, or does not exceed 300ppm, or does not exceed 200ppm, or does not exceed 100ppm, or does not exceed 50ppm, or does not exceed 25ppm, or does not exceed 10ppm. This ingestible composition can be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as soda water, etc.

[0179] In certain specific embodiments, the ingestible composition comprises a rebaudioside (e.g., rebaudioside A, rebaudioside D, rebaudioside E, rebaudioside M, or any combination thereof) and a flavor-improving compound. In some such embodiments, the introduction of the flavor-improving compound allows one to use 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) and still achieve the level of sweetness characteristic of a comparable product using more rebaudioside. In some embodiments, the concentration of the flavor-improving compound is 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, or no more than 25 ppm, or no more than 10 ppm. Such an ingestible composition may be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as soda and the like.

[0180] In some specific embodiments, the ingestible composition comprises acesulfame potassium and a flavor improving compound. In some such embodiments, the introduction of the flavor improving compound allows people to use less acesulfame potassium (e.g., reduce by more than 10%, reduce by more than 20%, reduce by more than 30%, reduce by more than 40%, reduce by more than 50%, reduce by more than 60%, or reduce by more than 70%), and still reach the sweetness characteristic level of comparable products using more acesulfame potassium. In some embodiments, the concentration of the flavor improving compound is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than 500ppm, or no more than 400ppm, or no more than 300ppmppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm. This ingestible composition can be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as soda or the like.

[0181] In some specific embodiments, the ingestible composition comprises rare sugar and flavor improving compound.In some such embodiments, the introduction of flavor improving compound allows people to use less rare sugar (e.g., reduce by more than 10%, reduce by more than 20%, reduce by more than 30%, reduce by more than 40%, reduce by more than 50%, reduce by more than 60%, or reduce by more than 70%), and still reach the sweetness characteristic level of comparable products using more rare sugar.In some embodiments, the concentration of flavor improving compound is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm.This ingestible composition can be any suitable form.In some embodiments, ingestible composition is food product, such as any one of those specifically listed below.In other embodiments, ingestible composition is beverage product, such as soda water etc.

[0182] In some specific embodiments, the ingestible composition comprises erythritol and flavor improving compound.In some such embodiments, the introduction of flavor improving compound allows people to use less erythritol (for example, reduce more than 10%, reduce more than 20%, reduce more than 30%, reduce more than 40%, reduce more than 50%, reduce more than 60% or reduce more than 70%), and still reach the sweetness characteristic level of the comparable product using more erythritol.In some embodiments, the concentration of flavor improving compound is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm.This ingestible composition can be any suitable form.In some embodiments, ingestible composition is food product, for example any one of those specifically listed below.In other embodiments, ingestible composition is beverage product, for example soda water etc.

[0183] In some specific embodiments, the ingestible composition comprises aspartame and flavor improving compound.In some such embodiments, the introduction of flavor improving compound allows people to use less aspartame (e.g., reduce by more than 10%, reduce by more than 20%, reduce by more than 30%, reduce by more than 40%, reduce by more than 50%, reduce by more than 60%, or reduce by more than 70%), and still reach the sweetness characteristic level of comparable products using more aspartame.In some embodiments, the concentration of flavor improving compound is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm.This ingestible composition can be any suitable form.In some embodiments, ingestible composition is food product, such as any one of those specifically listed below.In other embodiments, ingestible composition is beverage product, such as soda water etc.

[0184] In some specific embodiments, the ingestible composition comprises cyclamate and flavor improving compound.In some such embodiments, the introduction of flavor improving compound allows people to use less cyclamate (for example, reduce more than 10%, reduce more than 20%, reduce more than 30%, reduce more than 40%, reduce more than 50%, reduce more than 60% or reduce more than 70%), and still reach the sweetness characteristic level of the comparable product using more cyclamate.In some embodiments, the concentration of flavor improving compound is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm.This ingestible composition can be any suitable form.In some embodiments, ingestible composition is food product, for example any one of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as soda or the like.

[0185] In certain specific embodiments, the ingestible composition comprises mogrosides (e.g., mogroside III, mogroside IV, mogroside V, simanoside, isomogroside V, mogroside IVE, isomogroside V, mogroside IIIE, 11-oxomogroside V, the alpha isomer of isomogroside V, and any combination thereof) and a flavor-improving compound. In some such embodiments, the introduction of the flavor-improving compound allows one to use less mogroside (e.g., more than 10% reduction, more than 20% reduction, more than 30% reduction, more than 40% reduction, more than 50% reduction, more than 60% reduction, or more than 70% reduction) and still achieve the sweetness characteristic level of a comparable product using more mogrosides. In some embodiments, the concentration of the flavor improving compound is no more than 1000ppm, or no more than 900ppm, or no more than 800ppm, or no more than 700ppm, or no more than 600ppm, or no more than no more than 500ppm, or no more than 400ppm, or no more than 300ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 25ppm, or no more than 10ppm. This ingestible composition can be in any suitable form. In some embodiments, the ingestible composition is a food product, such as any of those specifically listed below. In other embodiments, the ingestible composition is a beverage product, such as soda water, etc. Additional mogroside compounds that can be appropriately used are described in U.S. Patent Application Publication No. 2017 / 0119032.

[0186] Therefore, in some embodiments, the composition described in any of the aforementioned forms (including in any use or method) comprises a flavor improvement compound and a sweetener. In some embodiments, the composition further comprises a vehicle. In some embodiments, the vehicle is water. In some embodiments, the flavor improvement compound is present at a concentration equal to or lower than its sweet taste recognition threshold.

[0187] 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 set forth in this paragraph, the sweetener is sucrose, fructose, glucose, xylitol, erythritol or a combination thereof.

[0188] In some other embodiments, the sweetener is present in an amount of 10ppm to 1000ppm. In some embodiments, the sweetener is present in an amount of 20ppm to 800ppm. In some embodiments, the sweetener is present in an amount of 30ppm to 600ppm. In some embodiments, the sweetener is present in an amount of 40ppm to 500ppm. In some embodiments, the sweetener is present in an amount of 50ppm to 400ppm. In some embodiments, the sweetener is present in an amount of 50ppm to 300ppm. In some embodiments, the sweetener is present in an amount of 50ppm to 200ppm. In some embodiments, the sweetener is present in an amount of 50ppm to 150ppm. In some further embodiments of the embodiments set forth in this paragraph, the sweetener is a derivative of steviol glycoside, mogroside, any of the foregoing, such as a glycoside derivative (e.g., glucosylation), or any combination thereof.

[0189] Composition can include any suitable sweetener or the combination of multiple sweetener.In some embodiments, sweetener is common sugar sweetener, such as sucrose, fructose, glucose and the sweetener composition of other syrups or sweetener concentrates that comprise natural sugar such as corn syrup (including high fructose corn syrup) or derived from natural fruit and vegetable source.In some embodiments, sweetener is sucrose, fructose or their combination.In some embodiments, sweetener is sucrose.In some other embodiments, sweetener is selected from rare natural sugar, including D-allose, D-psicose, L-ribose, D-tagatose, L-glucose, L-fucose, L-arabinose, D-turanose, and D-leucrose.In some embodiments, sweetener is selected from semi-synthetic " sugar alcohol " sweetener, such as erythritol, isomalt (isomalt), lactitol, mannitol, sorbitol, xylitol, maltodextrin etc. In some embodiments, the sweetener is selected from artificial sweeteners, such as aspartame, saccharin, acesulfame potassium, cyclamates, sucralose and alitame. In some embodiments, the sweetener is selected from the group consisting of cyclamic acid, mogroside, 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 hydrolysate (HSH), stevioside, rebaudioside A, other sweet steviosides, chemically modified steviol glycosides (such as glucosylated steviol glycosides), mogroside, chemically modified mogroside (such as glucosylated mogroside), guanidine sweetener (carrelame) and other guanidine sweeteners. In some embodiments, sweetener is a combination of two or more sweeteners set forth in this paragraph. In some embodiments, sweetener can be a combination of two, three, four or five sweeteners disclosed herein. In some embodiments, sweetener can be sugar. In some embodiments, sweetener can be a combination of one or more sugars and other natural and artificial sweeteners. In some embodiments, sweetener is sugar. In some embodiments, sugar is cane sugar. In some embodiments, sugar is beet sugar. In some embodiments, sugar can be sucrose, fructose, glucose or a combination thereof. In some embodiments, sugar can be sucrose. In some embodiments, sugar can be a combination of fructose and glucose.

[0190] 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 hydrolysate (HSH), or other syrups or sweetener concentrates from natural fruit and vegetable sources, or semi-synthetic "sugar alcohol" sweeteners, such as polyols. In some embodiments, non-limiting examples of polyols include erythritol, maltitol, mannitol, sorbitol, lactitol, xylitol, isomalt, propylene glycol, glycerol (glycerine), threitol, galactitol, palatinose, reduced isomaltooligosaccharides, reduced xylo-oligosaccharides, reduced gentio-oligosaccharides, reduced maltose syrup, reduced glucose syrup, isomaltulose, maltodextrin, etc., as well as sugar alcohols or any other carbohydrates or combinations thereof that can be reduced without adversely affecting the taste.

[0191] The sweetener may be a natural or synthetic sweetener, including but not limited to agave inulin, agave nectar, agave syrup, amazake, brazzein, brown rice syrup, coconut crystals, coconut sugar, coconut syrup, date sugar, fructans (also known as inulin fiber, fructooligosaccharides or oligofructose), green stevia powder, stevia rebaudiana, rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside E, rebaudioside F, rebaudioside I, rebaudioside H, rebaudioside L, rebaudioside K, rebaudioside J, rebaudioside N, rebaudioside O, rebaudioside M and other stevia-based steviol glycosides, stevioside, stevioside extract, honey, Jerusalem artichoke (Jerusalem artichoke syrup, licorice root, monk fruit (fruit, powder or extract), lucuma (fruit, powder or extract), maple sap (including, for example, sap extracted from sugar maple (Acer saccharum), black maple (Acer nigrum), American red maple (Acer rubrum), silver maple (Acer saccharinum), Norway maple (Acer platanoides), ash maple (Acer negundo), bigleaf maple (Acer macrophyllum), roughtooth maple (Acer grandidentatum), Rocky Mountain maple (Acer glabrum), monochromatic maple (Acer mono)), maple syrup, maple sugar, walnut sap (including, for example, sap extracted from white walnut (Juglans cinerea), black walnut (Juglans nigra), ghost walnut (Juglans ailatifolia), walnut (Juglans regia)), birch sap (including, for example, sap extracted from paper birch (Betula papyrifera, yellow birch (Betula alleghaniensis), mountain birch (Betula lenta), river birch (Betula nigra), gray birch (Betula populifolia), weeping birch (Betula pendula), sycamore sap (e.g., sap extracted from Platanus occidentalis), ironwood sap (e.g., sap extracted from Ostrya virginiana), unrefined cane sugar (mascobado), molasses (e.g., blackstrap molasses), molasses sugar, monatin, monellin, cane sugar (also known as natural sugar, unrefined saccharose or sucrose),palm sugar, panocha, piloncillo, rapadura, raw sugar, rice syrup, sorghum, sorghum syrup, tapioca syrup (also called tapioca syrup), thaumatin, yacon root, maltose syrup, barley malt syrup, barley malt powder, beet sugar, cane sugar sugar, crystallized fruit juice crystals, caramel, carbitol, carob syrup, castor sugar, hydrogenated starch hydrolates, hydrolyzed canned fruit juice, hydrolyzed starch, invert sugar, anethole, arabinogalactan, concentrated grape juice, syrup, P-4000, acesulfame potassium (also known as acesulfame potassium or ace-K), alitame (also known as aclame), advantame, aspartame, baiyunosdie, neotame, benzamide derivatives, bernadame, canderel, carrelame and other guanidine sweeteners, vegetable fiber, corn sugar, coupling sugar, curculin, cyclamates, cyclocaryoside I I), demerara, dextran, dextrin, diastatic malt, dulcin, sucrol, valzin, dulcoside A, dulcoside B, emulin, enoxolone, maltodextrin, saccharin, estragole, ethyl maltol, glucin, gluconic acid, gluconic acid lactone, glucosamine, glucuronic acid, glycerol, glycine, glycyrrhizin, glycyrrhetinic acid monoglucuronide, golden sugar, brown sugar, golden syrup, granulated sugar, gynostemma pentaphyllum, hernandulcin, isomerized liquid sugar, jall ab juice, chicory root dietary fiber, kynurenine derivatives (including N'-formyl-kynurenine, N'-acetyl-kynurenine, 6-chloro-kynurenine), galactitol, litesse, ligicane, lycasin, N-(4-cyanophenyl)-N-(2,3-methylenedioxybenzyl)guanidineacetic acid (lugduname), guanidine, falernum syrup, mabinin I, mabinin II, maltol, crystalline maltitol (maltisorb), maltodextrin, maltotriol (maltotriol), mannosamine, miraculin, mizuame, mogrosides (including, for example, mogroside IV,mogroside V and neomogroside, mukurozioside, nano sugar, naringin dihydrochalcone, neohesperidin dihydrochalcone, nib sugar, black oligosaccharide, norbu, almond syrup, osladin, pekmez, pentadin, periandrin I, perillaldehyde, perillartine, petphyllum, phenylalanine, phloisosideside I, phlorodizin, phyllodulcin, polyglycitol syrup, polypodoside A, pterocaryoside A A), tert-butyl glycoside B, rebiana, refined syrup, rub syrup, rubusoside, selligueain A, shugr, simenoside I, siraitia grosvenorii, soy oligosaccharides, Splenda, SRIoxime V, steviol glycosides, steviol biosides, stevioside, strogins 1, 2 and 4, sucrose, sucrononate, sugar, sodium p-nitrophenylureidopropionate (suosan), phloridzin, super aspartame, tetrasaccharide, threitol, treacle, trilobtain, tryptophan and derivatives (6-trifluoromethyl-tryptophan, 6-chloro-D-tryptophan), vanilla sugar, heptyl heptol, birch syrup, aspartame-acesulfame, assugrin, and combinations or blends of any two or more thereof. ,

[0192] In other embodiments, the sweetener can 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 can be prepared by enzymatic transglycosylation reactions catalyzed by various enzymes with transglycosylation activity. In some embodiments, the modified sweetener can be substituted or unsubstituted.

[0193] Other sweeteners also include any two or more combinations of any of the aforementioned sweeteners. In some embodiments, the sweetener may include a combination of two, three, four or five sweeteners disclosed herein. In some embodiments, the sweetener may be sugar. In some embodiments, the sweetener may be a combination of one or more sugars and other natural and artificial sweeteners. In some embodiments, the sweetener is a caloric sweetener, such as sucrose, fructose, xylitol, erythritol or a combination thereof. In some embodiments, the ingestible composition does not contain (or in some embodiments) substantially does not contain stevia-derived sweeteners, such as steviol glycosides, glucosyl steviol glycosides or rebaudioside. For example, in some embodiments, the ingestible composition does not contain stevia-derived sweeteners, or contains stevia-derived sweeteners at a concentration of no more than 1000ppm, or no more than 500ppm, or no more than 200ppm, or no more than 100ppm, or no more than 50ppm, or no more than 20ppm, or no more than 10ppm, or no more than 5ppm, or no more than 3ppm, or no more than 1ppm.

[0194] The flavor improving compound can be present in the ingestible composition in any suitable amount. In some embodiments, the flavor improving compound is present in an amount sufficient to enhance the taste of the composition (e.g., enhance sweetness, reduce sourness, or reduce bitterness). Therefore, in some embodiments, the flavor improving compound concentration included in the ingestible composition is no more than 200ppm, or no more than 150ppm, or no more than 100ppm, or no more than 50ppm, or no more than 40ppm, or no more than 30ppm, or no more than 20ppm. In some embodiments, the flavor improving compound is present in a minimum amount, such as 1ppm or 5ppm. Thus, in some embodiments, the ingestible composition comprises a flavor improving compound in a concentration range of 1 ppm to 200 ppm, or 1 ppm to 150 ppm, or 1 ppm to 100 ppm, or 1 ppm to 50 ppm, or 1 ppm to 40 ppm, or 1 ppm to 30 ppm, or 1 ppm to 20 ppm, or 5 ppm to 200 ppm, or 5 ppm to 150 ppm, or 5 ppm to 100 ppm, or 5 ppm to 50 ppm, or 5 ppm to 40 ppm, or 5 ppm to 30 ppm, or 5 ppm to 20 ppm. In embodiments where a sweetener such as sucrose or fructose is present, the weight ratio of the sweetener to the flavor improving compound in the ingestible composition is 1000:1 to 50000:1, or 1000:1 to 10000:1, or 2000:1 to 8000:1.

[0195] In certain embodiments, the ingestible composition or sweetener concentrate may include any additional ingredient or combination of ingredients commonly used in food and beverage products, including, but not limited to:

[0196] Acids, including, for example, citric acid, phosphoric acid, ascorbic acid, sodium bisulfate, lactic acid, or tartaric acid;

[0197] bitter ingredients, including, for example, caffeine, quinine, green tea, catechins, polyphenols, robusta green coffee bean extract, green coffee bean extract, potassium chloride, menthol, or proteins (e.g., proteins and protein isolates from plants, algae, or fungi);

[0198] Coloring agents, including, for example, caramel, red #40, yellow #5, yellow #6, blue #1, red #3, purple carrot, black carrot juice, purple sweet potato, vegetable juice, fruit juice, beta-carotene, turmeric curcumin, or titanium dioxide;

[0199] preservatives, including, for example, sodium benzoate, potassium benzoate, potassium sorbate, sodium metabisulfite, sorbic acid, or benzoic acid;

[0200] Antioxidants including, for example, ascorbic acid, calcium disodium EDTA, alpha-tocopherol, mixed tocopherols, rosemary extract, grape seed extract, resveratrol, or sodium hexametaphosphate;

[0201] Vitamins or functional ingredients, including, for example, resveratrol, Co-Q10, omega 3 fatty acids, theanine, choline chloride (Citcoline), inositol, inulin (chicory root), taurine, ginseng extract, guarana extract, ginger extract, L-phenylalanine, L-carnitine, L-tartrate, D-glucuronolactone, inositol, bioflavonoids, echinacea, Ginkgo Biloba, yerba mate, flaxseed oil, Garcinia cambogia peel extract, white tea extract, ribose, milk thistle thistle extract, grape seed extract, pyridoxine hydrochloride (vitamin B6), cyanocobalamin (vitamin B12), niacinamide (vitamin B3), biotin, calcium lactate, calcium pantothenate (pantothenic acid), calcium phosphate, calcium carbonate, chromium chloride, chromium polynicotinate, cupric sulfate, folic acid, ferric pyrophosphate, iron, magnesium lactate, magnesium carbonate, magnesium sulfate, monopotassium phosphate, monosodium phosphate, phosphorus, potassium iodide, potassium phosphate, riboflavin, sodium sulfate, sodium gluconate, sodium polyphosphate, sodium bicarbonate, thiamine mononitrate, vitamin D3, vitamin A palmitate, zinc gluconate, zinc lactate, or zinc sulfate;

[0202] Clouding agents, including, for example, ester gums, brominated vegetable oil (BVO), or sucrose acetate isobutyrate (SAIB);

[0203] buffers, including, for example, sodium citrate, potassium citrate, or saline;

[0204] Flavorings (edible flavors), including, for example, propylene glycol, ethanol, glycerin, gum arabic (acacia gum), maltodextrin, modified corn starch, dextrose, natural flavorings, natural flavorings with other natural flavorings (natural flavoring WONF), natural and artificial flavorings, artificial flavorings, silicon dioxide, magnesium carbonate, or tricalcium phosphate; or

[0205] Starches and stabilizers, including, for example, pectin, xanthan gum, carboxymethyl cellulose (CMC), polysorbate 60, polysorbate 80, medium chain triglycerides, cellulose gel, cellulose gum, sodium caseinate, modified food starch, gum arabic (acacia gum), inulin, or carrageenan.

[0206] Ingestible compositions or sweetener concentrates may have any suitable pH value. In some embodiments, flavor-improving compounds at a wide range of pH values, such as from a relatively low pH value to a neutral pH value, enhance the sweetness of the sweetener. Lower and neutral pH values ​​include, but are not limited to, 2.5 to 8.5; 3.0 to 8.0; 3.5 to 7.5, and pH values ​​of 4.0 to 7; in certain embodiments, the compounds disclosed and described herein, alone or in combination, may enhance the perceived sweetness of a fixed concentration of sweeteners at low to neutral pH values ​​in a taste test with a compound concentration of 50 μM, 40 μM, 30 μM, 20 μM or 10 μM. In certain embodiments, the enhancement factor of the compounds disclosed and described herein, alone or in combination, at a relatively low pH is substantially similar to the enhancement factor of the compound at a neutral pH. This consistent sweet taste enhancement property over a wide pH range allows the compounds disclosed and described herein, alone or in combination, to be widely used in a variety of foods and beverages.

[0207] The ingestible composition according to any of the foregoing embodiments, in certain embodiments, further comprises one or more additional flavor-improving compounds, such as compounds that enhance sweetness (e.g., hesperetin, neohesperetin, phloretin, naringenin, glucosylated steviol glycosides, etc.), compounds that block bitterness, compounds that enhance umami taste, compounds that reduce sourness or licorice taste, compounds that enhance saltiness, compounds that enhance cooling effects, or any combination of the foregoing.

[0208] The ingestible composition according to any of the foregoing embodiments, in certain embodiments, further comprises one or more additional flavor-improving compounds, such as compounds that enhance sweetness (e.g., hesperidin, naringenin, glucosylated steviol glycosides, etc.), compounds that block bitterness, compounds that enhance umami taste, compounds that reduce sourness or licorice taste, compounds that enhance saltiness, compounds that enhance cooling effects, or any combination of the foregoing.

[0209] Thus, in some embodiments, the ingestible compositions disclosed herein comprise a flavor-improving compound according to any or a combination of the above embodiments in combination with one or more other sweet taste enhancing compounds. Such sweet taste enhancing compounds include, but are not limited to, naturally derived compounds such as hesperidin, naringenin, glucosylated steviol glycosides, or synthetic compounds such as 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 any compound described in U.S. Patent Application Publication No. 2017 / 0119032. The flavor improving compounds can be combined with such other sweetness enhancers in any suitable ratio (w / w) in the range of 1:1000 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, for example, 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:15 In some embodiments of any of the foregoing embodiments, the flavor improving compound is combined with a glucosylated steviol glycoside in any of the above ratios. As used herein, the term "glucosylated steviol glycoside" refers to the product of enzymatic glucosylation of a natural steviol glycoside compound. Glucosylation typically occurs via a glycosidic bond, such as an α-1,2 bond, an α-1,4 bond, an α-1.6 bond, a β-1,2 bond, a β-1,4 bond, a β-1,6 bond, etc. In some embodiments of any of the foregoing embodiments, the TM1 compound (or any edible 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 ratios described above.

[0210] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor-improving compound according to any or a combination of the above embodiments in combination with one or more umami enhancing compounds. Such umami enhancing compounds include, but are not limited to, naturally derived compounds such as (E)-3-(3,4-dimethoxyphenyl)-N-(4-methoxyphenethyl)acrylamide (ericamide), or synthetic compounds such as any of the compounds described in U.S. Pat. Nos. 8,735,081; 8,124,121; and 8,968,708. The flavor improving compound can be mixed with such umami enhancers in any suitable ratio (w / w) in the range of 1:1000 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, for example 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:1 2. 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 combination.

[0211] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor-improving compound according to any or a combination of the above embodiments in combination with one or more cooling enhancing compounds. Such cooling enhancing compounds include, but are not limited to, naturally derived compounds, such as menthol or its analogs, or synthetic compounds, such as any of the compounds described in U.S. Pat. Nos. 9,394,287 and 10,421,727. The flavor-improving compound can be in any suitable ratio (w / w) with such umami enhancers in the range of 1:1000 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, 1:13, 1:1 2. 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 combination.

[0212] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor-improving compound according to any or a combination of the above embodiments in combination with one or more bitter-blocking compounds. Such bitter-blocking compounds include, but are not limited to, naturally derived compounds such as menthol or its analogs, or synthetic compounds such as any of those described in U.S. Pat. Nos. 8,076,491; 8,445,692; and 9,247,759. The flavor improving compound can be mixed with such bitter blocking agent in any suitable ratio (w / w) in the range of 1:1000 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, for example 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:1 2. 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 combination.

[0213] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor improving compound according to any or a combination of the above embodiments in combination with one or more sour taste adjusting compounds. The flavor improving compound can be in any suitable ratio (w / w) with such sour taste adjusting compound in the range of 1:1000 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, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19 ... 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 combination.

[0214] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor improving compound according to any or a combination of the above embodiments in combination with one or more mouthfeel improving compounds. Such mouthfeel improving compounds include, but are not limited to, tannins, cellulosic materials, bamboo powder, and the like. The flavor improving compound can be in any suitable ratio (w / w) with such mouthfeel enhancers in the range of 1:1000 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, for example, 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:1 2. 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 combination.

[0215] In some further embodiments, the ingestible compositions disclosed herein comprise a flavor-improving compound according to any or a combination of the above embodiments in combination with one or more flavor-masking compounds. Such flavor-masking compounds include, but are not limited to, cellulosic materials, materials extracted from fungi, materials extracted from plants, citric acid, carbonic acid (or carbonates), and the like. The flavor-improving compound can be in any suitable ratio (w / w) with such a mouthfeel enhancer in the range of 1:1000 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, for example, 1:25, 1:24, 1:23, 1:22, 1:21, 1:20, 1:19, 1:18, 1:17, 1:16, 1:15, 1:14, 1:13, 1:1 2. 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 combination.

[0216] In some aspects related to the foregoing aspects and embodiments, the present disclosure provides the use of flavor-improving compounds for enhancing the flavor of flavored compositions, such as flavored products. Such flavored compositions may use any suitable flavoring agent (edible flavor), such as any of the above-mentioned flavoring agents.

[0217] Flavored products and concentrates

[0218] In certain forms, the present disclosure provides a flavored product comprising any of the compositions of the foregoing five forms. In some embodiments, the flavored product is a beverage product, such as soda, flavored water, tea, etc. In some other embodiments, the flavored product is a food product, such as yogurt.

[0219] In embodiments where the flavored product is a beverage, the beverage may be selected from the group consisting of an enhanced sparkling beverage, a cola, a lemon-lime flavored sparkling beverage, an orange flavored sparkling beverage, a grape flavored sparkling beverage, a strawberry flavored sparkling beverage, a pineapple flavored sparkling beverage, a ginger beer, a root beer, a juice, a fruit-flavored juice, a fruit drink, a nectar drink, a vegetable juice, a vegetable-flavored juice, a sports drink, an energy drink, a fortified water beverage, a vitamin-fortified water, a near-water beverage, a coconut water, a tea beverage, a coffee, a cocoa beverage, a beverage containing a milk component, a beverage containing a cereal extract, and a smoothie. In some embodiments, the beverage may be a soft drink.

[0220] In certain embodiments of any of the configurations and embodiments described herein involving a flavored product, the flavored product is a non-naturally occurring product, such as a packaged food or beverage product.

[0221] Other non-limiting examples of food and beverage products or formulations include sweetened coatings, frostings or icings of such products, or any entity included in the following: soups, dry processed foods, beverages, ready-to-eat foods, canned or preserved foods, frozen processed foods, refrigerated processed foods, snack foods, baked foods, confectionery, dairy products, ice cream, meal replacements, pasta and noodles, as well as sauces, dressings, condiments, baby foods and / or spreads.

[0222] In general, soups refer to canned / preserved, dehydrated, instant, refrigerated, UHT and frozen soups. For the purpose of this definition, soup refers to a food made from meat, poultry, fish, vegetables, grains, fruits and other ingredients, cooked in a liquid, which may contain visible fragments of some or all of these ingredients. It may be clear (as a stock) or thick (as a chowder), smooth, pureed or chunky, ready-to-eat, semi-concentrated or concentrated, and served hot or cold, as a first or main course or as a snack (sipping beverage) between meals. Soup can be used as a raw material for preparing other meal ingredients, ranging from broth (consommé) to sauces (cream- or cheese-based soups).

[0223] The Dehydrated and Cooking Foods category generally refers to: (i) cooking aid products, such as powdered, granulated, paste-like, concentrated liquid products, including concentrated bouillon, bouillon and bouillon-like products in pressed, tableted or powdered or granulated form, sold individually as finished products or as ingredients in products, sauces and recipe mixes (regardless of technology); (ii) dietary solution products, such as dehydrated soups and freeze-dried soups, including dehydrated soup mixes, dehydrated instant soups, dehydrated ready-to-eat soups, dehydrated or self-heating preparations of ready-made dishes, meals and single-serving entrees, including pasta, potatoes and rice; and (iii) dietary garnish products, such as condiments, marinades, salad dressings, salad toppings, dips, mixes, batter mixes, shelf-stable sauces, barbecue sauces, liquid recipe mixes, concentrates, sauces or sauce mixes, including salad recipe mixes, sold as finished products or as ingredients in products, whether dehydrated, liquid or frozen.

[0224] Beverages generally refer 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 concentrates for preparing beverages (e.g., soda), and dry powder beverage precursor mixtures. Beverages also include alcoholic beverages, soft drinks, sports drinks, isotonic beverages and hot drinks. Alcoholic beverages include but are not limited to beer, cider / perry, FABs, wine and spirits. Soft drinks include but are not limited to carbonated beverages, such as cola and non-cola carbonated beverages; fruit juices, such as fruit juices, honey drinks, fruit drinks and fruit-flavored drinks; bottled water, including soda water, spring water and purified / table water; functional beverages, which can be carbonated or still beverages, including sports drinks, energy drinks or elixir drinks; concentrates, such as ready-to-drink liquids and powder concentrates. Beverages, whether hot or cold, include, but are not limited to, coffee or iced coffee, such as fresh, instant and blended coffee; tea or iced tea, such as black, green, white, oolong and flavored teas; and other beverages, including flavored, malt-based or plant-based powders, granules, blocks or tablets mixed with milk or water.

[0225] Snacks generally refer to any food that is a simple, informal meal, including but not limited to sweet and salty snacks and snack bars. Examples of snacks include but are not limited to fruit snacks, potato chips / crisps, extruded snacks, tortillas / corn chips, popcorn, pretzels, nuts and other sweet and salty snacks. Examples of snack bars include but are not limited to granola / cereal bars, breakfast bars, energy bars, fruit bars and other snack bars.

[0226] The baked goods category generally refers to any edible product whose preparation process involves exposure to heat or excessive sunlight. Examples of baked goods include, but are not limited to, bread, buns, cookies, muffins, cereals, toaster pastries, cakes, waffles, tortillas, soft cookies, pies, bagels, tarts, quiches, cakes, any baked goods, and any combination thereof.

[0227] Ice cream generally refers to frozen desserts containing cream, sugar and flavorings. Examples of ice cream include, but are not limited to: impulse ice cream; family-packed ice cream; frozen yogurt and handmade ice cream; soy, oat, bean (such as red bean and mung bean) and rice-based ice cream.

[0228] Candy generally refers to edible products that taste sweet. Examples of candy include, but are not limited to, hard candy, gelatin, chocolate candy, granulated candy, chewing gum, etc. and any combination of products.

[0229] The meal replacement category generally refers to any food that is intended to replace a normal meal, especially for those who are concerned with health or fitness. Examples of meal replacements include, but are not limited to, weight loss products and recovery products.

[0230] The ready-to-eat food category generally refers to any food that can be consumed as a meal without extensive preparation or processing. Ready-to-eat foods include products to which the manufacturer has added recipe "skills" so that they have a high degree of readiness, completeness, and convenience. Examples of ready-to-eat foods include, but are not limited to, canned / preserved, frozen, dried, refrigerated ready meals; dinner mixes; frozen pizza; refrigerated pizza; and prepared salads.

[0231] The Pasta and Noodles category includes any pasta and / or noodles, including but not limited to canned, dried, and refrigerated / fresh pasta; and regular, instant, refrigerated, frozen, and snack noodles.

[0232] The canned / preserved foods category includes, but is not limited to, canned / preserved meat and meat products, fish / seafood, vegetables, tomatoes, beans, fruits, ready meals, soups, pasta and other canned / preserved foods.

[0233] 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.

[0234] The dry processed food category includes, but is not limited to, rice, dessert mixes, dry ready meals, dehydrated soups, instant soups, dry 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 boxes, fresh-cut fruit, ready meals, pizza, prepared salads, soups, fresh pasta, and noodles.

[0235] The Sauces, Dressings and Condiments category includes, but is not limited to, tomato sauces and purees, bouillon / stock cubes, herbs and spices, monosodium glutamate (MSG), table sauces, soy-based sauces, pasta sauces, wet / cooking sauces, dry sauces / powder mixes, ketchup, mayonnaise, mustard, salad dressings, vinaigrettes, dips, pickles and other sauces, dressings and condiments.

[0236] The baby food category includes, but is not limited to, milk- or soy-based formulas; and prepared, dry, and other baby foods.

[0237] Spreads include, but are not limited to, jams and preserves, honey, chocolate spreads, nut spreads and yeast spreads.

[0238] Dairy products generally refer to edible products produced from the milk of mammals. Examples of dairy products include, but are not limited to, drinking milk products, cheese, yogurt and sour milk drinks, and other dairy products.

[0239] Additional examples of flavored products, particularly food and beverage products or formulations, are provided below. Exemplary ingestible compositions include one or more candies, chocolate candies, chocolate chips, chocolate slabs (countlines), bagged chocolate bars (selflines) / softlines, boxed assortments, standard boxed assortments, twist-wrapped miniature chocolates, flavored chocolates, chocolates with toys, sandwich cookies, other chocolate candies, mints, standard mints, strong mints, hard candies, pastilles, gums, jellies and chews, toffees, caramels and nougats, medicated candies, lollipops, liquorice, other candies, breads, packaged / industrial breads, bulk / artisan breads, pastries, cakes, packaged / industrial cakes, bulk / artisan cakes, cookies, chocolate coated Layer biscuits, Sandwich biscuits, Filled biscuits, Salty crackers and crackers, Bread substitutes, Breakfast cereals, Ready-to-eat cereals, Family breakfast cereals, Flakes, Muesli, Other cereals, Children's breakfast cereals, Hot cereals, Ice cream, Ready-to-eat ice cream, Single-serve dairy ice cream, Single-serve water ice cream, Multi-serve dairy ice cream, Multi-serve water ice cream, Family-serve ice cream, Family-serve dairy ice cream, Ice cream desserts, Bulk ice cream, Family-serve water ice cream, Frozen yogurt, Artisan ice cream, Dairy products, Milk, Fresh / Pasteurised milk, Whole fresh / Pasteurised milk, Semi-skimmed fresh / Pasteurised milk, Long-life / UHT milk, Whole long-life / UHT milk, Semi-skimmed long-life / UHT milk, Fat-free Long-life / UHT milk, goat's milk, condensed / evaporated milk, plain condensed / evaporated milk, flavoured, functional and other condensed milk, flavoured milk drinks, dairy only flavoured milk drinks, flavoured milk drinks with fruit juice, soy milk, yoghurt drinks, fermented milk drinks, coffee creamers, milk powder, flavoured milk drinks, cream, cheese, processed cheese, spreadable cheese, unspreadable processed cheese, unprocessed cheese, unprocessed cheese spread, hard cheese, packaged hard cheese, unpackaged hard cheese, yoghurt, plain / natural yoghurt, flavoured yoghurt, jelly yoghurt, probiotic yoghurt, drinkable yoghurt, regular drinkable yoghurt, probiotic drinkable yoghurt, frozen and shelf-stable snacks, dairy-based snacks, soy-based desserts, frozen snacks, fresh cheese and quark , Fresh cheese and quark cheese, plain, fresh cheese and quark cheese, flavored, fresh cheese and quark cheese, savory, sweet and savory snacks, fruit snacks, chips / crisps, puffed snacks, tortilla chips / corn chips, popcorn, pretzels, nuts, other sweet and savory snacks, snack bars, granola, breakfast bars, energy bars, fruit bars, other snack bars, meal replacements, weight loss products, recovery drinks, ready meals, canned ready meals, frozen ready meals, dried ready meals, frozen ready meals, dinner mixes, frozen pizza, refrigerated pizza, soups, canned soups, dehydrated soups, instant soups, cold soups, hot soups, frozen soups, pasta, canned pasta, dry pasta, frozen / fresh pasta, noodles, plain noodles, instant noodles,Noodles in cups / bowls, Noodles in bags, Frozen noodles, Snack noodles, Canned foods, Canned meat and meat products, Canned fish / seafood, Canned vegetables, Canned tomatoes, Canned beans, Canned fruit, Canned ready meals, Canned soups, Canned pasta, Other canned foods, Frozen foods, Frozen processed red meat, Frozen processed poultry, Frozen processed fish / seafood, Frozen processed vegetables, Frozen meat substitutes, Frozen potatoes, Oven-baked potato chips, Other oven-baked potato products, Non-oven frozen potatoes, Frozen baked foods, Frozen desserts, Frozen ready meals, Frozen pizza, Frozen soups, Frozen noodles, Other frozen foods, Dried foods, Dessert mixes, Dried ready meals, Dehydrated soups, Instant soups, Dried pasta, Vegetarian noodles, Instant noodles, Noodles in cups / bowls, Noodles in bags, Refrigerated foods, Refrigerated processed meats, Refrigerated fish / seafood products, Refrigerated processed fish, Refrigerated fish, Refrigerated coated fish, Refrigerated smoked fish, Refrigerated lunches bags, refrigerated ready meals, refrigerated pizza, refrigerated soups, refrigerated / fresh pasta, refrigerated noodles, oils and fats, olive oil, vegetable and seed oils, cooking fats, butter, margarine, spreads and fats, functional spreads and fats, seasonings, sauces and condiments, tomato pastes and purees, bouillon / stock cubes, stock cubes, gravy granules, liquid stocks and stocks, 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, vinaigrette, dips, pickles, other sauces, seasonings and condiments, baby food, formula, standard formula, growing-up formula, toddler formula, hypoallergenic formula, infant formula foods, dried baby food, other baby food, spreads, jams and preserves, honey, chocolate spreads, nut-based spreads and yeast-based spreads. Exemplary ingestible compositions also include candies, baked products, ice cream, dairy products, sweet and savory snacks, snack bars, meal replacement products, ready meals, soups, pasta, noodles, canned foods, frozen foods, dry foods, refrigerated foods, oils and fats, baby foods or spreads or mixtures thereof. Exemplary ingestible compositions also include breakfast cereals, sweetened beverages or solid or liquid concentrate compositions for preparing beverages, ideally enabling the reduction of previously known sugar sweeteners or artificial sweeteners in concentration. ,

[0240] Some embodiments provide chewable compositions that may or may not be swallowed. In some embodiments, the chewable composition may be gum, chewing gum, saccharified gum, sugarless gum, functional gum, bubble gum, which contain the compounds disclosed and described herein, alone or in combination.

[0241] Typically, a sweet receptor modulating amount, a sweet receptor ligand modulating amount, a sweet flavor modulating amount, a sweet flavoring amount, a sweet flavor enhancing amount, or a therapeutically effective amount of one or more compounds of the present invention are added to an ingestible composition, optionally in the presence of a sweetener, so that the sweet flavor-modified ingestible composition has increased sweetness as judged generally by humans or animals, or, in the case of formulation testing, by a majority of a panel of at least eight human taste testers using procedures well known in the art, compared to an ingestible composition prepared without the compounds of the present invention.

[0242] In some embodiments, the compounds disclosed and described herein regulate the sweetness or other taste properties of other natural or synthetic sweeteners and the ingestible compositions prepared therefrom, either alone or in combination. In one embodiment, the compounds disclosed and described herein can be used or provided alone or in combination with their ligand-enhanced concentrations. For example, the amount of the compounds disclosed and described herein, either alone or in combination, can be 0.001ppm to 100ppm, or a narrower alternative range of 0.1ppm to 50ppm, 0.01ppm to 40ppm, 0.05ppm to 30ppm, 0.01ppm to 25ppm, 0.1ppm to 30ppm, or 0.1ppm to 25ppm, or 1ppm to 30ppm, or 1ppm to 25ppm.

[0243] In some embodiments, the flavor improving compounds disclosed and described herein can be provided in the form of flavoring concentrate preparations, either individually or in combination, such as being suitable for subsequent processing to produce ready-to-use (i.e., ready-to-eat) products. "Flavoring concentrate preparations" refer to preparations that should be reconstituted with one or more dilution media to become ready-to-use compositions. The term "ready-to-use composition" is used interchangeably with "ingestible composition" herein, and it represents any substance that can be taken orally, whether alone or together with another substance, whether intended for or not for consumption. In one embodiment, the ready-to-use composition includes a composition that can be directly eaten by a human or animal. The flavoring concentrate preparation is usually used by mixing or diluting with one or more dilution media, such as any edible or ingestible ingredient or product, to impart or change the dilution medium with one or more flavorings. Such a use process is generally referred to as reconstitution. Reconstitution can be carried out in a domestic environment or an industrial environment. For example, a consumer can reconstitute a frozen fruit juice concentrate in a kitchen with water or other aqueous media to obtain a ready-to-use fruit juice beverage. In another example, soft drink syrup concentrate can be reconstituted with water or other aqueous media on a large-scale industrial scale by manufacturers to produce instant soft drinks. Since the concentration of the flavoring or seasoning that the flavoring concentrate preparation has is higher than the instant composition, the flavoring concentrate preparation is usually not suitable for direct consumption without reconstitution. There are many benefits to using and producing the flavoring concentrate preparation. For example, one benefit is to reduce the weight and volume of transportation, because the flavoring concentrate preparation can be reconstituted by adding a suitable solvent, solid or liquid when using.

[0244] The flavored product according to any of the preceding embodiments, in certain embodiments, further comprises one or more additional flavor-improving compounds, such as compounds that enhance sweetness (e.g., hesperidin, naringenin, glucosylated steviol glycosides, etc.), compounds that block bitterness, compounds that enhance umami taste, compounds that reduce sourness, compounds that enhance saltiness, compounds that enhance cooling effects, or any combination of the foregoing.

[0245] In certain embodiments of any of the forms and embodiments described herein involving a sweetening or flavoring concentrate, the sweetening or flavoring concentrate is a non-naturally occurring product, such as a composition specifically manufactured for the production of a flavored product, such as a food or beverage product.

[0246] In one embodiment, the flavoring concentrate formulation comprises i) a compound disclosed and described herein, either alone or in combination; ii) a carrier; and iii) optionally at least one adjuvant. The term "carrier" refers to a generally inactive auxiliary substance, such as a solvent, adhesive, or other inert medium, which is used in combination with the compounds of the present invention and one or more optional adjuvants to form a formulation. For example, water or starch can be a carrier for the flavoring concentrate formulation. In some embodiments, the carrier is the same as the dilution medium used to reconstitute the flavoring concentrate formulation; in other embodiments, the carrier is different from the dilution medium. As used herein, the term "carrier" includes, but is not limited to, an acceptable carrier for ingestion.

[0247] The term "adjuvant" means an additive that supplements, stabilizes, maintains or enhances the expected function or efficacy of an active ingredient such as the compounds of the present invention. In one embodiment, at least one adjuvant comprises one or more flavoring agents. Flavoring agents can have any flavor known to those skilled in the art or consumers, such as chocolate, coffee, tea, mocha, French vanilla, peanut butter, milk tea (chai), or the flavor of a combination thereof. In another embodiment, at least one adjuvant comprises one or more sweeteners. One or more sweeteners can be any sweetener described in the present application. 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. Patent No. 6,468,576, the entire contents of which are incorporated herein by reference for all purposes.

[0248] In one embodiment, the flavoring concentrate preparation of the present invention can be selected from the form of liquid, solid, foam material, paste, gel, emulsion and their combination including solution and suspension, for example, liquid containing a certain amount of solid content. In one embodiment, the flavoring concentrate preparation is a liquid form including water-based and non-aqueous. In some embodiments, the flavoring concentrate preparation of the present invention can be carbonated or non-carbonated.

[0249] The flavoring concentrate formulation may further include a freezing point depression agent, a nucleating agent or both as the at least one adjuvant. A freezing point depression agent is an acceptable compound or agent for ingestion, which can reduce the freezing point of a liquid or solvent to which the compound or agent has been added. That is, the freezing point of a liquid or solution containing a freezing point depression agent is lower than the freezing point of a liquid or solvent without a freezing point depression agent. In addition to reducing the initial freezing point, a freezing point depression agent can also reduce the water activity of the flavoring concentrate formulation. Examples of freezing point depressants include, but are not limited to, carbohydrates, oils, ethanol, polyols such as glycerol and combinations thereof. A nucleating agent represents an acceptable compound or agent for ingestion that can promote nucleation. The presence of a nucleating agent in the flavoring concentrate formulation can improve the mouthfeel of slush, and helps maintain the physical properties and performance of slush at freezing temperatures by increasing the number of required ice crystal centers. Examples of nucleating agents include, but are not limited to, calcium silicate, calcium carbonate, titanium dioxide and combinations thereof.

[0250] In one embodiment, the flavoring concentrate formulation is formulated to have a low water activity to extend shelf life. Water activity is the ratio of the vapor pressure of water to the vapor pressure of pure water in the formulation at the same temperature. In one embodiment, the water activity of the flavoring concentrate formulation is less than about 0.85. In another embodiment, the water activity of the flavoring concentrate formulation is less than about 0.80. In another embodiment, the water activity of the flavoring concentrate formulation is less than about 0.75.

[0251] In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 2 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 5 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 10 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 15 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 20 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 30 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 40 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 50 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the present invention in the flavoring concentrate formulation is at least 60 times the concentration of the compound in the ready-to-use composition. In one embodiment, the concentration of the compound of the invention in the flavoring concentrate formulation is up to 100 times the concentration of the compound in the ready-to-use composition.

[0252] The sweetened or flavored concentrate according to any of the foregoing embodiments, in certain embodiments, further comprises one or more additional flavor-improving compounds, such as compounds that enhance sweetness (e.g., hesperidin, naringenin, glucosylated steviol glycosides, etc.), compounds that block bitterness (e.g., eriodictyol, homoeriodictyol, 7-O-methyleriodictyol (sterubin) and its salts or glycoside derivatives, and vanillyl lignans, such as matairesinol and other compounds described in PCT Publication No. WO2012 / 146584), compounds that enhance umami taste (e.g., rubemamine, rubescenamine, (E)-3-(3,4-dimethoxyphenyl)-N-(4-methoxyphenethyl) acrylamide, etc.), compounds that reduce sourness and / or licorice taste, compounds that enhance saltiness, compounds that enhance cooling effects, or any combination of the foregoing.

[0253] Preparation method

[0254] The compounds disclosed herein can be synthesized by the methods described below, or by modifications to these methods. The methodological modifications include temperature, solvents, reagents, etc., known to those skilled in the art. In general, during any of the methods for preparing the compounds disclosed herein, it may be necessary or desirable to protect sensitive or reactive groups on any of the molecules involved.

[0255] In certain forms, the present disclosure provides a method for preparing a flavor-improving compound of the aforementioned form by an enzyme-catalyzed process. For example, in certain embodiments, the method includes providing a precursor, which is a flavanone or a derivative thereof, having a hydrogen atom at the 3-position of the central flavanone bicyclic ring system. Suitable non-limiting examples of flavanone precursors include hesperidin, naringenin, eriodictyol, homoeriodictyol, 7-O-methyleriodictyol (sterubin) or any salt or glycoside thereof. In certain embodiments, the method includes reacting a 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-functionalized flavanone compound. In some embodiments, the one or more enzymes provide functionalization of a specific stereochemical form 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 an enzyme, a flavanone 3-hydroxylase. In some embodiments, the 3-functionalized flavanone compound can be further functionalized at the 3-position. For example, in some embodiments where the flavanone compound functionalized at the 3-position has a hydroxyl group at the 3-position, the hydroxyl group can be further functionalized using any reagent suitable for reacting with the 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 maintains the absolute stereochemistry at the 3-position.

[0256] In some specific embodiments of the foregoing, the method includes providing naringenin (e.g., in a suitable solvent system); reacting naringenin with flavanone 3-hydroxylase to form aromandrin [(2R,3R)-3,5,7,4'-tetrahydroxyflavanone]; reacting aromandrin with acetic acid (or an ester thereof) to form aromandrin-3-O-acetate [(2R,3R)-3-acetoxy-5,7,4'-trihydroxyflavanone].

[0257] Example

[0258] To further illustrate the present invention, the following examples are included. Of course, these examples should not be construed as specifically limiting the present invention. Variations of these embodiments within the scope of the claims are within the capabilities of those skilled in the art and are considered to fall within the scope of the present invention as described and claimed herein. The reader will recognize that a skilled artisan and a person skilled in the art having grasped this disclosure will be able to prepare and use the present invention without exhaustive examples.

[0259] Example 1 - Sweetness Enhancement

[0260] The test compound (2R,3R)-3-acetoxy-5,7,4'-trihydroxyflavanone (A01) was tested for its sweetness enhancement of a 5% (w / w) sucrose aqueous solution compared to naringenin. 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 and the presence of any licorice taste in the samples on a scale of 0 to 10. The results are listed in Table 1.

[0261] Table 1

[0262] <![CDATA[ Enhancement ]]> <![CDATA[ Sweetness (0-10) ]]> <![CDATA[ Licorice taste (0-10) ]]> No flavor improvers / enhancers 5.0 0.0 +50ppm Naringenin 5.8 0.5 +10ppm A01 8.0 2.0 +5ppm A01 7.0 1.0

[0263] Example 2 - Sweetness Enhancement

[0264] Test compound A01 was compared to other sweetness enhancers in a test similar to that described in Example 1. The results are listed in Table 2. The comparative compounds were dihydroquercetin (taxifolin) 3-O-acetate (A02) and dihydromyricetin (ampelopsin) 3-O-acetate (A03).

[0265] Table 2

[0266] <![CDATA[ Enhancement ]]> <![CDATA[ Sweetness (0-10) ]]> <![CDATA[ Licorice taste (0-10) ]]> No flavor improvers / enhancers 5.0 0.0 +20ppm A01 8.8 1.5 +20ppm A02 6.8 2.0 +20ppm A03 5.1 0.0

[0267] Example 3 - Sweetener Replacement Test

[0268] Test Compound A01 was used in combination with certain sweeteners to achieve a sweetness profile comparable to a comparable beverage containing a higher concentration of sweetener and no amount of Test Compound A01.

[0269] In one test, 45 panelists were asked to choose between a beverage sweetened with 450 ppm of Rebaudioside M and a beverage sweetened with 300 ppm of Rebaudioside M and 12 ppm of test compound A01. Of the 45 panelists, 23 chose the former and 22 chose the latter, which was statistically equivalent. This suggests that the introduction of 12 ppm of test compound A01 can reduce the concentration of Rebaudioside M by 33%.

[0270] In another test, 45 panelists were asked to choose between a beverage sweetened with 160 ppm sucralose and a beverage sweetened with 120 ppm sucralose and 12 ppm test compound A01. Of the 45 panelists, 22 chose the former and 23 chose the latter, which was statistically equivalent. This suggests that the introduction of 12 ppm of test compound A01 can reduce the concentration of sucralose by 25%.

[0271] Example 4 - Preparation of compounds by biotransformation and chemical synthesis

[0272] The following description sets forth a non-limiting method for obtaining Compound A01.

[0273] Protein production

[0274] The gene encoding flavanone-3-hydroxylase (F3H) from Arabidopsis thaliana (GenBank: U33932) was sequenced with its original gene sequence (only the Xho restriction site was removed) and codon optimized for E. coli with and without an N-terminal Trx tag from Twist (cloned into pET29a via restriction sites NcoI and XhoI). E. coli BL21Star (DE3) was transformed with the four constructs.

[0275] For pre-culture, 7mL LB culture medium containing kanamycin (50 μ g / mL) was inoculated with the E. coli BL21Star (DE3) strain carrying the construct, and overnight at 200rpm at 37°C. The main culture of 400mL LB culture medium containing kanamycin (50 μ g / mL) was inoculated with 5mL pre-culture, and incubated at 37°C until the optical density at 600nm (OD600) reached about 0.8. The expression of AthF3H was induced by 0.1mM IPTG (isopropyl-D-thiogalactopyranoside), and the culture was shaken at 20°C for 20 hours. Cells were harvested by centrifugation, and then resuspended in 100mM potassium phosphate buffer (KPi, pH7) to OD of 50. Protein production was confirmed by SDS-PAGE, which showed that AthF3H was well expressed in the form of soluble protein, and there was no difference in four structures.

[0276] Biotransformation

[0277] Biotransformation was performed with whole cells of E. coli BL21Star(DE3)-AthF3H at OD10 in a total volume of 150 mL 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 for 3 h at 30° C. The biomass was removed by centrifugation.

[0278] Purification of naringenin and unreacted naringenin.

[0279] The supernatant of the biotransformation was poured onto a pre-treated Waters Oasis HLB SPE column (6 g). Retention was complete and the column was rinsed with water. It was then successfully eluted by three volumes of 100 mL H2O / EtOH, 50:50 (fractions 1 to 3) and three volumes of H2O / EtOH, 30:70 (fractions 4 to 6). Fractions 1 and 2 were filtered, combined, evaporated, and then freeze-dried to give 102 mg of 90% pure naringenin (molar yield 59%). Similarly, fractions 4 and 5 produced approximately 60 mg, which was pure unreacted naringenin. α D = +21° (c = 0.5 g / 100 mL, EtOH) indicated that the unreacted naringin was (2R)-(+)-naringenin. Similarly, the produced naringenin showed α D = +9° (c = 0.5 g / 100 mL, EtOH), indicating that the major product was of (2R, 3R) configuration.

[0280] Synthesis of citrus aurantium-3-O-acetate

[0281] Citrus aurantifolia (100 mg) and 10 mg of dimethylaminopyridine (DMAP) were diluted in pyridine (10 mL). Acetic anhydride (1 mL) was added dropwise. The reaction was stirred for 15 minutes. Pyridine was evaporated and the reaction was added to 100 mL of EtOAc, washed with 5% KHSO4 and brine. It was dried over sodium sulfate and evaporated. The crude product was diluted in 10 mL of CH2Cl2 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 with 5% KHSO4 and water in turn. The aqueous phase was extracted twice with CH2Cl2. The combined organic phase was dried over sodium sulfate and evaporated. The crude product was purified by flash chromatography on Lichroprep RP-18 (45 g glass column) using a gradient of water / acetonitrile 0.1% formic acid (20%, 5 minutes, then 20-80% B, 20 minutes). The fractions containing the expected product were combined, evaporated and freeze-dried to give 53 mg of citronellal-3-O-acetate (59% yield). Optical rotation α D = +22.1° (c = 0.5 g / 100 mL, EtOH) showed that the product was (2R, 3R)-(+)-aurantifolia-3-O-acetate. 13 C(MeOD,500MHz):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).

[0282] Example 5 - Natural mixture testing

[0283] In some cases, it may be desirable to obtain Compound A01 from a natural source where it can be extracted as a mixture with other flavonoid compounds.

[0284] Hydrolysis of Engelhardtia Roxburghiana Extract

[0285] In a 500 mL three-necked round-bottom flask equipped with a mechanical stirrer and a condenser, 25 g of Engelhardtia Roxburghiana extract (80% astilbin, supplier 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, once with brine, dried over sodium sulfate, filtered and evaporated to give 14.4 g of crude Engelhardtia hydrolysate (88.3% yield).

[0286] Acetylation of Engelhardtia Hydrolysate by Reactive Distillation

[0287] In a 500mL three-necked round-bottom flask equipped with Vigreux 15cm, a distillation bridge and a magnetic stirrer, 10g of crude Engelhardtia hydrolyzate, 200mL AcOH and about 100mg vitamin E were refluxed for 50 hours. Acetic acid was subsequently distilled and the reaction mixture was diluted in about 200mL ethyl acetate. The organic phase was washed with 200mL 5% sodium bicarbonate, washed once with water, washed once with brine, dried over sodium sulfate, filtered and evaporated to obtain 10g yellow-brown powder (87.5% yield).

[0288] Quantification of flavonoid compounds

[0289] The UPLC instrument was a Waters Acquity I-Class UPLC system consisting of a binary pump, PDA detector, column manager (4 columns), fixed loop sample manager, and ELSD detector. The mass spectrometer was a QExactive Plus (Thermo). The instrument was calibrated no more than 2 weeks ago using Thermo infusion solution. The method 4-P-FS-Huangqi-MeOH was used (described above). For quantification, ion 305.0654 ( 1 )、289.0706( 2 )、347.0761( 3 )、331.0815(4 ) was used to give a secondary calibration curve. The UV range used was 270-320 nm to give a linear calibration curve. By dissolving exactly 10.88 mg of 1 , 10.15mg 3 , 10.13mg 2 and 10.05 mg 4 The sample was prepared by diluting the stock solution ten-fold in ethanol, which is the highest point of our calibration curve. The 100 ppm solution was then diluted to make six calibration points in the range of 100 ppm to 1 ppm (100:50:25:10:5:1). Approximately exactly 10.0 mg of the resulting mixture was diluted into 10.0 mL of ethanol. The solution was diluted 5-fold for quantification (approximately 200 ppm). Table 3 shows the composition of some flavonoids in the resulting mixture.

[0290] Table 3

[0291] Compound %UV <![CDATA[Dihydroquercetin 1 > 12.3％ <![CDATA[Nobiletin 2 > 7.5％ <![CDATA[Dihydroquercetin 3-OAc 3 > 41.5％ <![CDATA[Nobiletin 3-OAc 4 (Compound A01)]]> 20.0％

[0292]

[0293] Sensory evaluation

[0294] The resulting mixture was introduced into water containing 5% sucrose, and 50 ppm of the mixture was about as sweet as 20 ppm of pure compound A01.

[0295] Example 6 - Sweetness Enhancement

[0296] The test compound (2R,3R)-3-acetoxy-5,7,3'-trihydroxy-4'-methoxyflavanone (A02) was tested for sweetness enhancement and as a sweetener.

[0297] In one test, taste panelists were asked to choose between a beverage sweetened to 9Bx with sucrose and a beverage sweetened to 7Bx with sucrose and 2.5ppm of the test compound A02. The panelists rated the two beverages as being equally sweet. This demonstrates that the introduction of 2.5ppm of the test compound A02 can reduce the sucrose concentration by 2Bx.

[0298] 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 10 Bx. Panelists chose the former beverage as tasting sweeter and found that the combination of rebaudioside M and test compound A02 imparted a natural sweetness similar to that of the beverage sweetened with sucrose to 12 Bx.

Claims

1. Use of a flavor improving compound for enhancing the sweetness of an ingestible composition comprising a sweetener selected from sucrose, fructose, glucose, sucralose or any combination thereof, and the ingestible composition does not contain any steviol glycosides, Wherein the flavor improving compound is a compound of formula (Ib) or a salt thereof, Alternatively, the flavor improving compound is a compound of formula (Id) or a salt thereof.

2. The use according to claim 1, wherein the flavor improving compound is present in the ingestible composition at a concentration ranging from 1 ppm to 50 ppm based on the total weight of the ingestible composition.

3. An ingestible composition comprising a sweetener selected from sucrose, fructose, glucose, sucralose or any combination thereof, and the ingestible composition does not contain any steviol glycosides, is a non-naturally occurring composition and comprises a flavor improving compound at a concentration of not more than 200 ppm, Wherein the flavor improving compound is a compound of formula (Ib) or a salt thereof, Alternatively, the flavor improving compound is a compound of formula (Id) or a salt thereof.

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