as) United States cz) Patent Application Publication co) pub. No.: US 2022/0304348 AL US 20220304348A1 FREROT et al. (43) Pub. Date: Sep. 29, 2022 (Sa) TRITERPENE GLUCURONIDES AND THEIR G0) Foreign Application Priority Data USE AS FLAVOR MODIFIERS, eb. 6, 2020 (EP) 201559508 (71) Applicant: Fiemenich SA, Satigzny (C1) (72) Inventors: Exe VERNE! REROT, Satigny (C1); Tim Satigny (CH); Isabelle CAYEUX, Satuny (CH); Christine SAINELEGER, Satizny (CH Dattatreya BANAVAR, Plinsboro NI US) (73) Assignee: Firmenich SA, Sotizay (CLD) QI) ApplNos — 1164072 (22) PCT Filed: Dee, 14,2020 (86) PCTNos — PCTTEP2020/086027 $371 XD). ()Date: | Mar. 4, 2022 Related US. Application Data (60) Provisional application No, 62/952,529, fled on Doe 23, 2010. Publication Class 6) mea. AZiL 2780 (2006.01) ca7t 6200 (200601) A231 2700 (2006.01) (2) US.cL cox A2BL 27/36 (201608). COTS 63/008 (2013.01); 4232 2724 (2016.08) 231.2786 (2016.08), 4231. 2788 (2016.08) on ABSTRACT The present disclosure generally provides tnitepene ght curonides, and the use of such compounds and related compounds as lavor modifies. In some sspevs, the dsc sure provide certain compositions that include such trier pene glucuronides, such as compositions that inelide such Trterpene vcaronides snd one of more othee sweeteners. In some other aspects, the dielosure provides methods of reducing the eslorie content of a sweetened antl, such a8 1 swcctened food oF beverge predict.Patent Application Publication Sep. 29, 2022 US 2022/0304348 AI FIG.1US 2022/0304348 AL ‘TRITERPENE GLUCURONIDES AND THEIR USE AS FLAVOR MODIFIERS ‘CROSS-REFERENCE TO RELATED APPLICATIONS, [0001] The present application claims the benefit of pri- borty of US. Provisional Application No. 62°952,529, filed Dee. 23, 2019, and Puropean Patent Application No. 20155050.8, fled Feb. 6, 2020, both of which are hereby Jncomporatecl by reference as though se forth herein in tir entireties, TECHNICAL FIELD [0002] The present disclosure generally provides tite: pene glicuronides, sich as monpglocuronitles and dighs furonides, and the ure of such compounds and related compounds a5 Ravor modifiers. In some aspects, the dscl- sure provides certain compositions that include soch tte pene glucuronides, such a8 compositions that include such 'sterpene glacaronides and one of more other sweeteners. some other aspects, the dislosure provides methods of reducing the calorie content of @ wostened article, stich 2 1 swectened food oF bevernge peo. DESCRIPTION OF RELATED ART [0003] The taste system provides sensory information about the chemical composition ofthe external world. Taste teansduction is one of the more sophisticated forms of chemically triggered sensation in animals. Signaling of taste {is found throughout the animal kingdom. fom simple met Zoans to the most complex of vertcrates, Mammals are believed 10 have five basie taste modalities: soo, biter, sour, sly, and mami [nnd], Sscetnss isthe taste most commonly perceived ‘when eating foods rich in sigars, Mammals generally per vive sweetness f0 be a pleasurable sensation, except in excess, Calorie sweeteners, such as sberose a fetose, are the prototypical examples of sweet substances, Although variety of no-clorie and los-calore substitutes exis, these caloric sweeteners are sill the predominant means by which tomestible products induce the perception of sweetness "upon consumption. [MONS]. Metaholic disorders and related conditions, such obesity, diabetes, and carliovascular disease, are. major pbc health eancerms throughout the world. And their provalence is increasing at alarming rates in almost every ‘developed county. Calorie sweeteners are a key contributor to this tend, a they are included in various packaged food tnd beverage products to make them more palatable 10 ‘consumers. In many cases, no-carie or low-calorie subst tutes can he wed in foods and beverages in place of sucrose or fructose. Even so, these compounds impart sweciness diferent from caloric sweeteners, and a numberof con: ‘mers fal to view thom as suitable alternatives. Moreover, Such compounds may be dient incorporate ino eentin products. In some instances, they may Be used as partial Fepliacements for ealorc sweeteners, bul their mere presence can cause many consumers to perceive unpleasant ofF-astes including, astringeney, bittemess, and metalic und licorice tastes. Thus, lowercalorie sweeteners fice certain chal lenges to their adaption. [0006] Swecotness enhancement provides an alternative Approach to overcoming some of adoption challenges faced Sep. 29, 2022 by lowercalorie sweeteners. Such compounds ca be used jn combination with sterose of fructose to ealiance their sweetness, thereby permiting the use of lower quantities of uch caloric swesteners in various food or beverage prod: ucts But in addition to enhancing the perccived swcctness bf the primary sweetener, such compounds nevenhoess alter the perceived taste ofthe sweetener. Thus, many consumers find that i less pleasurable to eonsume such sweetness- enhanced products in comparison (0 unentanced altema- tives having higher calories. Ths, there isa continuing nee to discover compouds that enhance the sweetness of ealoric swocteners without altering their perceived taste in a way that detrets fom the pleasure that consumers experience in eating or drinking proxies containing such sweeteners. SUMMARY {0007} ‘The present disclosure estes to the discovery that ceria compeunds exhibit desirable and surpsing set ness enhancing elect when combined with primary sweet ners at amouins elective to enhance swectness {0008} in first aspect, the disclosure provides flavor. modifying. compounds, which are Tiree monogh euoaides of dighcurnides. In some eatbodinests, the Toorce monoglvuroides or diglacurnides include Tieo- rice mondglaronids, whic reformed hy emoving one or mone alicuronide motes from licorice. poly cirnides #0 form orice monoglucuronides oF dight curds 10009} Ina second aspect, the disclosure provides avoe- ‘odiing compounds, which ae compounds of forma or sas there, wherein [0010] _R’ isa hydrogen stom, —OH, or —O—R; [0011] RM is Cy. alkyl, which is optionally substituted ‘one of more times by substituents selected from the group consisting of OH and Cg alkoxy: 10012] Ris a hydrogen stom, —OH, or -O-R* [0013] Ris C,, alkyl, which is optionally substituted ‘one of more times by substituents selevted from the group consisting of OH and Cy. alkoxy; oF R?* is —C(O} (Cy.calkyD or a glucosyl moiety: 10014} Risa hydrogen atom, a ghoeurony] moiety, 8C,.« alkyl ghucuronyl ester moiety, ora glocosy! moiety: 0015] one of Rand R is a methyl group, andthe other Is COOK;US 2022/0304348 AL [0016] Ris a hydrogen atom, aC,,. alkyl, @ plucuronyl moiety Cally glveuronyl ester moiety, ora lcos} et [0017] Risa hydrogen atom or C, «alkyl; and foots} X!is CH, or C—O. In some further embodiments thereof, the Havor-moditying compounds ate compounds of formula (a): or sls threo, wherein: [0019] "R’jsaliydogca atom, —OH, or ORY; [0020] R'is Cy al which is opinaly substied fone of more tics by sbstiwents selected Som the group Consisting of OH sod C,, alkoxy [0021] R-jsalydogen som, — O11, or ~O—R° and 10022] 2s Cy ay which is optionally substted one or more tines by substituents slete from the Boop consning of OH aod C, alkoxy 10023] In some emexliment ofthe foregoing. embodi- ‘ents, atleast one of Rand Ris nota droge atom. In Some sich embodiments, one of Rand Rei a hydrogen fom, and the teri ther no a hydogen to [0024] Ina thied aspect the disclosure proves uses of any favor modifying’ compounds of the’ fist or sesond pects. 10025] Ia fourth aspect, the disclosure provides uses of Say fhwvorsmodilving compounds of the fist oF second fpects to enkance the swtners ofan ingstible eomposi= don. In some embedincas thereof, the iagestible compo Sion comprises a calorie swestener In some other embed tons thor the ingesible composition comprises 4 nom Caloric stone. In some embodiment, the swectener a high-intensity swestener 10026] Tha thaspet, he disclosure provides ses f any Aavor-mosising compounds ofthe fistor second aspects 0 reduce the souress ofan ingestible composition. [W027] In inh aspect, the disclosure provides uses of any flavor-modiiving compounds of the fist or send spats o rade the iternes ofan ingestibie composition [0028] Ina seventh aspect, the disclosure provides uses of any flavorsmoditying compounds of the fist or second Aspects inthe manufacture ofan ingestible competion to enhance the sweetness of the ingestle composition. In Some embeoiments there. the ingestble composition come prises 8 caloric sncstencr. In some other eubodinnts thereof, the ingestble composition comprises a non-core sweetener In some embodiment the swestene high Sep. 29, 2022 Jnensity sweetener. In an ehh aspect, the disclosure provides uses of any favor-modifying compounds of the first or second aspects in the manufacture ofan ingestible composition to rede the soumess ofthe ingesile com position 10020] In a ind aspect, the disclosure provides uses of any Ahvormoditying compounds of the fist or second spect in the manufacture ofan ingestible composition 0 recioe the hitemess ofthe ingestible compos 10030] In a tenth aspect, the disclosure provides methods of enhancing the swectaess of an ingestible composition, comprising introducing an amount (uch as a sweetness enhaheing effective anount) of any compounds of the fist for second aspects tothe ingestible composition. Ina elev- eth aspect, the disclosure provides methods of reducing the sourness of an ingestible composition, comprising intodue- Jing! an amount (Guch as a. soumess-reducing. effective mount) of any compounds of the first or second aspects to the ingestible composition, 10031] In a twelfth aspect, the disclosure provides meth- cds of reducing the bitemess of an ingestible composition, comprising initoducing an amount (such as a bittemess reclaing effective amount) of any compounds ofthe fist or second aspects to the ingesible composition. 10032] Ina thirteen aspect, the disclosure provides com Positions comprising any compounds of the fst or second "specs. Ia some embodiments, the compounds ofthe fist or second aspects make up at least 20% by weight of the ‘compositions on a dry weight basis (eq. based on the total ‘weight of the composition excluding the weight of any liguid carrer) In a fourteenth aspect, the disclosure provides te compositions comprising any compounds of the first or second aspects, wherein the compounds of the fst or ‘up at least 20% by weight of the fe compositions, based on the total weight of com position {034 ‘ble compositions comprising any compounds ofthe fist or Ina fifteenth aspect, the disclosure provides ingest- sccond aspects, wherein fon ofthe compounds ofthe first or second aspacts in the ingestible compositions js mo more than 200 ppm. In some embodiments, the Jngestible composition is not a naturally occurring compo: [0035] In a sixteenth aspect, the disclosure provides ngestible compositions comprising any compounds of The first or second aspects and a sweetener. In some embodi- rms, the sweetener isa calorie sweetener, sich s sires, fructose, glucose, xylitol, erthrtel, or combinations thereof. In some embodiments, the sweetener is non caloric swectener, such asa steviel glycoside, a mogroside, aspartame, sveralose, aesulfame K. saccharin, of any com binations thereof. In. some embodiments, the ingestible composition comprises one or more high-intensity sweoten- 10036] In an seventeenth aspect, the disclosure provides @ concentrated sweetening composition comprising any con pounds of the fist or second aspects and & sweeten, 0037] In an eighteenth aspect, the diselosure provides Favored prodvets comprising any composition of the pre- coding five aspects, In some embodiment, the Mvored products are beverage products, such as soda, Mavored Irate, tea, and the like. In some other embodiments, the Favored products are food products, suchas yogurtUS 2022/0304348 AL {0038} In a nineteenth aspect, the disclosure provides ‘methods of making compounus of the fis or second aspects, ‘comprising: providing a licorice polyglacuronide, and com icting the licorice polyglacuranide with an enryme 10 romove one or more glucuronide moieties to form a from a licorice monoglacuronide. In some embodiments, futher funetionalization is caried us [0039] Further aspects, and embodiments thereof ae set orth below in the Detaled Description, the Drawings, the Abstract, and the Claims, BRIEP DESCRIPTION OF THE DRAWINGS [0030] |The following drawings ae provided for purposes bf illstrating various embodiments ofthe compenitions ad ‘methods diselosed herein, The drawings are provided for illustrative purposes only, and are not intended to describe any preferred compositions or preferred methods, ort serve fs.# source of any limitations on the scope of the claimed inventions [0041] FIG. 1 shows a chemical formula that represents ‘non-limiting examples of eompounds (or salts thers) dis: ose herein, wherein: Risa hyogen stom, hydroxy or ‘an optionally substinved alkoxy; Reis a hydrogen atom, hydroxy, an optionally substituted alkoxy, an alkoxyearbo: ayloxy, ora glocosyloxy; R'is a hydrogen atom, a glucur: yl, a glucuronyl este, ora glucosyl: one of R* and R° is a methyl group, and the other is —C(O)-O—R™:R™ is a hydrogen atom, a Cy. alkyl @ glucuronyt moiety @ Cg alkyl alucuronyl ester moiety, ora glucosyl moiety: R® is 8 hydrogen atom or C, alkyl; and X" ig —CH,—or »C=0. DETAILED DESCRIPTION 10042] The following Detailed Description sts forth vati= ‘ts aspocts and embodiments provided herein, The descrip- fon iso be read fiom the perspective of the person of ‘ondinary skill inthe relevant af. Therefore, information that fs well known to such olinarily skilled artisans is not necessarily included Definitions 10043] The folowing tomas and phrases have the mesa ings indicated below, unless otherwise provided herein. This dlslosure may employ other terms and phrases not expressly defined herein. Soh other terms and phases have the meanings that they would possess within the context of this disclosure to those of ordinary skill inthe at. In some instances, aterm or phrase may be defined in the singular or plural In such instances, it i understood that any term i the Singular may include its plural counterpart and vice vers, tunless expressly indicated tothe contrary [0044] As usod herein, “solvate” means @ compound ormcd by the interaction of one or more solvent molecules ‘and one or more compounds described herein. In. some embodiments, the solvates are ingestibly acceptable sol vate, such as hydrates. [0045] As used herein, °C, 10 C,” oF °C,” in which “a” and” ae integers, refer to the numberof carbon atoms in the specified yroup, ‘That i, the group ean eontin fom “a” 10" inclusive, carbon atoms, Thus, for example, 8 °C, 10 C, ally” or *C,4 alll group refers to all alkyl groups having from 1 10-4 carbons, that is, CHy—. CH,CH,—, CHACHCH,—. (CH),cH—, CH,CH,CHLCH,— CHSCHCH(CH,)— and (CH). Sep. 29, 2022 0046] As used herein, “alkyl” means straight or branched hydrocarbon chin that is Tully sated (2, contains no double or triple bonds). In some embodiments, alkyl group has 1 to 20 carbon atoms (whenever it pears herein, «niierical range such asl to 20" refers 19 cach integer in the given range: ¢ "I to 20 carbon atoms” means tht the allyl group may consist of I earbon stom, 2 carbon atoms, 3 carbon afoms, ete, up to and ineluding 20 earbon atoms, although the present definition also cover the ‘eeurence ofthe tem “alk” where no numerical range it designated). ‘The alkyl group may also be a medium size alkyl having 1 to 9 carbon toms. The alkyl group could also bea lower aly! having 1 0 4 carbon atoms. The all may be designated as "C, ally” o similar designations By way of example only, “C14 alky” indicates tha there ae ‘ne To four eazboo atoms in the alkyl chain, ie, the alkyl chain selected from the group consisting of methyl, ethyl, propyl so-propy n-butyl, iso-buty, sec-butyl, and t-butyl ‘Typical alkyl groups include, but are in no way limited to, rnicthyl, ethyl, propyl. sopropsl, buts, isobutyl, tia butyl pentyl, hexyl, andthe lke. Unless indicated tothe contrary the term “aiky?” refers toa group that isnot further substrate, 10047] As used herein, “alkoxy” means a moiety of the formula OR wherein is an alkyl, as is defined above, suchas “C;.» alkoxy", including bt not limited to methoxy, ethoxy, n-propoxs, I-methylethoxy (isopeopony n-bulony, Jso-butoxy, see-buioxy, and tet-butoxy, and the like. 0048] As used herein, a “zlucosy! moiety” is « monova leat moiety in which one of he hydroxyl groups of glucose js replaced by a bond to another atom, functional soup, or moiety. Unless otherwise specified the ghicose can have any Suitable stereochemistry. 10049] Thus, the term incldes moieties having D stereo- chemisty, as well at moieties having [ stereochemisry. Further, the term ineludes moieties having a stereochemi- try. a5 Well a moictcs having steeochemisty. The carbon atoms of the glocosy! moiety follow the conventional mun bering, as shown below. The diagram is shown for [D> lucose, but applies in an analogous way to glucosyl moi- ‘ies having andor L stereochensistey” 0050] As wsed herein, a “ylucuronyl moiety” is a mon valent moiety ia which oe of the hydroxyl groups of lucuronic acid is replaced by a bond 10 another atom, fimetional group, or moiety. Unless otherwise specified, the slucuronic acid can have any suitable stereochemistry. Thus, the tem inclodes moieties having D stereochemistry, as well 8 mojtios having 1 sterochemistry. Further, the tom Includes moieties having a stewochemistry, as wel 2 moi- ies ving stereochemistry. The carbon atoms of the lurucoay! moiety follow the conventional numbering, as shown below, The diagram is shown for f-D glucuronic acid, but applies in an analogous way to glucurony moicties having «candor 1 stereochemistryUS 2022/0304348 AL The disclosure refers toa °Cy.g alkyl glucuroay! ester moiety." which refers toa glucuronyl moiety (as defined in this paragraph) in which the carboxylic acid group of fhucuronie acid has @ Cy, alkyl group in place of the hydrogen atom of te carboxylic acid proup. In any of the embodiments below, the C,.g alkyl moiety can have any suitable value, such as metiyl, ell, isopropyl, propyl, butyl, pentyl, and the lke. In some embodiments, the Cy. aly moiety ismethyL In some other embodiments, theC, ¢ ‘kyl moiety is eth. IMQS1] It isto be understood that certain radical naming conventions can inclede either a mono-odical or adic radial, depending on the context. For example, where ‘substituent requies 0 points of attachment fo the rest of| the molecule, itis understood that the substituent is. Airadial. For example, a substituent identi as ak that requires two points of attachment includes di-radicals such ae—CHl,, CHCl, —CH1,CH(CH, CH, and the Tike. [0052] Wherever a substiwent is depicted as diac Ge bas 040 points of attachment to the rest of the mol cule), itis t9 be understood thatthe substituent can be fttached in any directional configuration unless otherwise Indicated. Thus, for example, 2 substituent depicted as «AE se includes the substimont being oriented such that the A is attached at the lefimost attachment point ofthe molecule as well as the case in which Ais attached at the sighimost tachment point of the molecule. [o0s3] A “sweetener”, “swoet Havering favor eniy", or “sweet compound” herein refers 10 a ‘compound or ingestibly acceptable salt thereof that eis a detectable sweet avor in a subject, eg. a compound that fsctivates TIR2/TIRS receptor in vito [0084] As used herein, the singular forms “a.” “an.” and “the” include plural referents unless the context clearly dictates otherwise. For example, relerence to “a substituent” encompasses a single substituent as well as two oF more substituents, and the like. As used herein, "Yor example, “Toe instance,” “Such as." oF “ineluding” are meant to introduce examples that frther clarify more general subject matter, Unless otherwise expressly indicated, such examples are provided only as an aid for understanding embodiments illustrated inthe present disclosure, and are not meant to be Timiting in any fashion. Nor do these phrases indicate any Kind of preference for the diselosed embodiment. 1055] “As used herein, “comprise” or “comprises” or comprising” o "comprised of refer to groups that re open, Sep. 29, 2022 ‘meaning thatthe group can include addtional members in !udition those expressly recited. For example, the phrase, “comprises A” mens that A mst be presen, but that other members can be present too. The tems “include.” “have.” tnd “composed of” and their grammatieal variants have the ‘same meaning. In contrast, “consis of" or “consists of” or “oonsisting of” refer to groups that are closed. For example, the phrase “consists of A” means that A and only A is preset 10056] As used herein, “optionally” means that the subs sequently described event(s) may or may not occur. In some tembodiments, the optional event dees not occur ln some other embodiments, the optional event does occur one or 10057] As used herein, Yor” is to be given reasonable interpretation, and is not w be limited to an eitheror construction, Ths, the phrase “comprising Aor B” ‘cans that A can be present and not Bo that Bis present tnd not A ofthat and Bare both present. Further, fA, for example, delines # class that ean have multiple members, feg.,A, and A,, then one of more members of the elass can be present concurrent, 10058] As used herein, certain substituents or linking roups having only a single atom may be refered wo by the fname of the atom, For example, in some cases, the substitu- ent —H' may be rofered to a5 “hydrogen” or “a hydrogen stom,” the substituent "—P" may be refered to a “Hlvorine” fora Mworine atom,” an the linking group" -O-—" may be referred to a “oxygen!” or “an oxygen aon, 10059] Pins of attachment for groups are generally ind cated by a tenminal dash (—) or by an asterisk (*). For example, a group such as *—CH,—CH, of CH CH, both represent an ethyl group 10060] Chemical structures are often shown wsing the “aeleta” format, such that carbon atoms are not explicitly shown, and hydrogen atoms attached to carbon atoms are omitted entirely. For example, the structure broadest ~ represents butane (ie, a-butane). Furthermore, romatic roups, such as benzene are represented by showing one of the contributing resonance structures. For example, the sveture represents toluene 10061] Other tems sre defied in other portions of this description, even though not included in this subsection,US 2022/0304348 AL Licorice Glucuronides [0062] In a first aspect, the dislosure provides flavor ‘modifying compounds, which ate licorice glucuronides. As used herein, the term “licrice glucuronide” refers t© a lueuronide of ay ofthe tepene compounds (or derivatives thereof) fond in ticorice (Gipeyrrhica glabra). This ‘includes any such compounds that exist naturally a the plant 8 particular ghicuronides, as well as glicuronide deriva tives of terpenes that exist inthe plant in other forms (e2, 1s fee terpenes, or as diffren-order glucuronides of the same). Thus, the tenn “licorice glucuronide” does nt imply that such compounds are necessarily extactd from licorice, or that they are derived from compounds that are extracted ‘rom licorice, This, while such compounds can be extracted fiom licorice or derived from compounds extracted from Fieorce, they ean also be synthesized using typical organic reactions enzyme-catalyzed transformation, oF any combi- nation thereof For example in some embodiments, “licorice lucuronides” are synthesized by a process that comprises in vitro enzyme-ctalyzed reactions. [063] In some embodiments, the iarice glucuronides ae licorice monoglvcuronides. Such compounds may be extracted from licorice, or may be derived from by other means. For example, in some embodiments, licorice mono- Sep. 29, 2022 tlucuroaides are syathesized vi the hydrolysis of licorice Aiglucuronides (ex, through the removal of one ghi- ccuronide moiety trom plyeyrizin by hydrolysis). In some embodiments, the licorice monoghicuronides are Fcorice texpene monoglucuronides, such as monoglucuronides of terpene compounds present in Ticorice (oF derivatives ‘hereo, In some further embodiments, the Hieorice mono- alucuronides are Ticorice triterpene monoglucuronides, such as monoghicuronides of triterpene compounds present in Ficorice (or derivatives thereo, such 2s monoglucuronides of elyeybetinie acid, oF derivatives thereof 10064] Table 1 sets forth various examples of licorice slucuroaides. In some embodiments, the Hcorice ghi- curonides comprise Compound 101. In some embodiments, the licorice glucuronides comprise Compound 102. In some embodiments, the licorice glucuronides comprise Com- pound 103. In some embodiments, the licorice glucuronides comprise Compound 104, In some embodiments, the lic rice glucuronides comprise Compound 108. embodiments, the licorice glucuronides comprise Com- pound 106. In some embodiments, the licorice glucuronides comprise Compound 107. TABLEUS 2022/0304348 AI Sep. 29, 2022 TABLE t-continuedUS 2022/0304348 AI Sep. 29, 2022 TABLE t-continued , Ss ; esUS 2022/0304348 AI TABLE t-continued , Ss | Sep. 29, 2022US 2022/0304348 AI Sep. 29, 2022 TABLE t-continued 0m, Hn, 10" oH Obey an eteUS 2022/0304348 AL ‘TABLE t-continued eo my 8. 10" Yo heya ety eer [065] Ina second aspect, the disclosure provides Navor ‘modifying compounds, which are compounds of formula A or sas thereof wherein 10066] “Rs a ydogen atom, O11, or ORs [0067] Rs C, alk, Which is optionally sbstuted one or more tim by sbsttuents select nb the group consisting of OH al, alkoxy 10068] "RY sa ydogca fom, OH, or ~O—R°*; 10069] R248 Cy al which is optionally substited one oF more times by subsitents selected fom the group consisting of OH and Cy. alkoxy; of Ris C(O} {Casall} ora glucosyl maiey: [W070] Risa hydrogen stom, a plocwoasl moiety 8C. alkyl ghicuonyl ester moiety, or a glucosyl moiety: {007} one of R* and Risa methyl group, and the other 8 —CO)_0-R [0072] Ris hydrogen stom, Cc allyl a lucwras! soit C,. alkyl alvcuonyl ester oie or plveosl moi 10073] i074] R® isa hydrogen atom FC slkyl and X!is CH, — or 5-0, Sep. 29, 2022 10075] The variable R* can have any suitable value, sccording 1 the embodiments set forth above, In some embodiments, Risa hydrogen atom. Insome other embodi- ments, R'is an OH] moiety In some other embodiments, R'js-O—R™. When Ris not hydrogen atom, the point of attachment is a slereoventer, and the Mat connection Jndiates that R" may be connected in a way’ such that the configuration around te stereocenter is either an R or an S configuration. In some such embodiments, R'is connected jn.a way such tht the configuration around the sereoceater an R configuration. la some other such embodiments, js connected in away such that the configuration around the ‘Meroocenter ian S configuration, R can have any suitable value secording the embodiments set forth above. In some embodiments, R'is an unsubstituted C,., alkyl, such a8 methyl ethyl, or isopropyl. In some further such embodi- sens, R'is methyl 10076] The variable R? can have any suitable value, sccording 10 the embodiments set forth above. In some embodiments of any of the above embodiments, R° is hydrogen atom. ln some other embodiments of any of the above embodiments, Ris an —OH moiety. In some other embodiments of aay’ of the above embodiments, R? is —O—R™, R* can have any suitable value according tthe embodiments set forth above. In some embodiment, R= is fan unsubstituted C,,, alkyl, such as methyl, ethyl, 0 iso- propyl. In some further such embodiment, Ris methyl 10077]. The variable R® can have any’ suitable valve, sccording 1 the embodiments set forth above, In some embodiments of any of the above embodiments, R° is 8 hydrogen atom. In some other embodiments of any of the above embodiments, R° is a glucuronyl moiety. In some ‘uch embodiments, the glueurony! moiety of R connects via fn ether Tinkage, with the attachment to the ghicuronyl ‘moiety of R® occurring atthe I-postion earbon, the 20- sivon carbon, the 3-position carbon, or the 4-position carbon of said moiety. in some further such embodiments, the plucuroay! moiety of R* connects via an ether linkage, with the attachment fo the glacurony] moiety of R° occurring atUS 2022/0304348 AL uw the I-position carbon, In some other embodiments of any of the above embodiments, R'is a Cy. glucuronyl ester moi cy, In some such embodiments, the C;,g glucurony! ester moiety of R? connects via linkage glycosidic bond, with the atachment w the C,. ghucuroayl ester moiety of R* occur fing at the I-postion carbon, the 2-posiion carbon, the 5 position carbon, othe 4-position earn of ssid moiety. In some Further such embodiments, the C,.. glueuronyl ester riety of R? connects via linkage glycoside band, with the attachment to the C,.C—0 (a carbonyl x0up). [0081] In some embodiments oF any ofthe above embod ‘ments, the Havor- modifying compounds are compounds of | formula (la 0082] or salts thereof, wherein: 0083] Ris a hydrogen stom, OH, or ORM: T0084] R'is C4 alkyl, which is optionally substituted ‘ne ot more times by substituents selected from the group consisting of —OH and C,. alkoxy: 0085] isa hydrogen stom, —OH, or —O—R™ and 10086] Ris C,, ally, which is optionally substicaed ‘ne ot more times by substituents selected from the group consisting of OH and C,.. alkoxy. In. some further embodiments thereof, R'is "OH and R? is a hydrogen stom. In some other embodiments thereof, R's a hydrogen fiom and R° is OI. In some other embodiments thera, R'is Ol and R” is OIL. [0087] Where the compounds disclosed herein ave at least one chiral center, they may exist a individual enan- tomers und diastereomers ors mixtures of ch isomers. In some embodiments in connection with the second aspect, the sweet-enhaneing compound his substantial enantiomeric purity 10088] Scparstion of the individual isomers or scloctive synthesis of the individual isomers is accomplished. by application of various methods which ate well Known 10 Practitioners in the art. Unless otherwise indicated (eg, where the stereochemistry of a chiral center is explicitly showin), all sich isomers and mixtures thereof sre ince in the seope of the compounds disclosed herein. Purther ‘more, compounds disclosed herein may exis in one or more talline or amorphous forms. Unless otherwise indicated, such forms are inluded in the seope of the compounds disclosed herein including any polymompie forms. In ad tion, some of the compounds disclosed herein may’ foam solvates with water (ie, hydrates) or common organic folvenls, Unless otherwise indicated, such solvates are Jnchaded in the scope of the compounds disclosed hercin 0089] The skilled arsan will recognize tha some src= tures deseribed herein may’ be resonance forms oF aomers of compounds that_may be faiiy represented by other chemical stuctures, even when kinetically the asa ree- ‘opnizes that such structures may only represen «very stallUS 2022/0304348 AL 12 portion of sample of such compound(s). Such compounds fre considered witin the scope ofthe structures depicted, though such resonance forms or taulomers are not repre sented herein. 10090] "Isotopes may he present in the compounds ‘described. Hach chemical clement as represented ina com pound structure may inchide any isotope of sai element. For example, 3 compound sutures hydrogen atom my be explicitly disclosed or understood to be present in the compound. At ny position af the compound tat a hydrogen ‘tom may be present, the hydrogen atom can be any isotope of hydrogen including but not limited 19 hydrogen-I (pro- jum) and bydroges-2 (deuterium). Ths, reference herein 10 ‘compound encompasses all potential isotope forms unless the context clearly dictates otherwise, [0091] Ia some embodiments. the compounds disclosed herein are capable of forming acd andor base salts by vie of the presence of amino andor carboxy! groups or groups Similar thereto, Physiologically accepiable acid adicon salts can be formed with inorganie acids und onzanic acids. Inonuanie acids from which salts can be derived include, for ‘example, hydrochloric acid, hydrebromic acid, sulfurie acid, nitric eed, phosphoric aid, and the like, [0092] Onsunie acide trom which salts can be derived Include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid oxalic acid, maleic acid, malonic acid, Suocinic aid, fumarie acid, tartaric acd, etic acid, benzoic acid, cinnamic acid, mandslc acid, methanesulfonie acid, ‘ethanesulfonie acid, pioluenesilonic acid, salicylic acid, and the like, Physiologically aeeeptabe sls ean be formed Using inorganic and onzanic bases. Inowanie bases from ‘which salts can be derived include, for example, bases that ‘contain sodium, potassium, lithium, ammonium, calcium, ‘magnesium, ion, zine, copper, manganese, aluminum, and the like, particularly preferred are the ammonium, potas sium, sodium, caleium and. magnesium salts. In. some ‘embodiments, treatment ofthe compounds dislosad herein with an inorganic base results in Toss of a labile hydrogen from the compound to afford the sat form including an jnorganic eation such as Li*, Na", K*, Mge* and C the like. Onzanic hases from which salts can be derived include, for example, primary, sccondary, and tertiary ami- nes, substituted amines ineluding naturally occurring sub- stituted amines, eyelic amines, basic ion exchange resins, ‘andthe like, specially such as isopropylamine, rimeth- ylamine, diethylamine, wiethylamine, tripropylamine, and ‘ethanolamine. In some embodiment, the sills are comest bly acceptable salts, which arc salts suitable for inclusion i comesible food andlor beverage products, Uses and Methods [0093] In another aspect, the disclosure provides uses of Any Mavor-modifying compounds of the foregoing aspects, including any embodiments or combination of embodiments thersof. as set forth above. In certain related aspects, the disclosure provides uses of any favor modifying com pounds of the foregoing aspects, including any embodiments ‘r combination of embodiments thereof, asset forth above, to enfiance the sweetness of an ingestible compeniton, In some embodiments thereof, the ingestible eompostioncon- prises a sweetener, sch a a calorie sweetener. In certain other related aspects, the disclosure provides uses of any avor-modifving compounds of the foregoing aspects, inchding any embodiments or combination of embodiments Sep. 29, 2022 thereof, 28 set forth above, o reduce the soumess of an Jngesible composition. In another related aspect, the dis- closure provides uses of any favor-melfying compounds of the foregoing aspects, including any embodiments or com- bination of embodiments thereof, as set forth above, 19 recive the hitters ofan ingestible composition Incenain thor related aspects, the disclosure provides uses of any’ Aavormodifying. compounds of the foregoing aspects, Jnchiding any embodiments oF combination of embodiments thereof, asset Forth above, in the manufacture of an ingest ‘ble componiton to enhance the sweetness oF the ingesible fon. In some embodiments thereof, the ingestible tion comprises a calorie swestener. In another related aspect, the disclosure provides uses of any’ flavor ‘modifying compounds of foregoing aspects, including ay embodiments or eambination of embodiments thereof, s set forth above in the manufacture ofan ingestible composition to reduce the soumess of the ingestible composition. In smother related aspect, the disclosure provides uses of any favor-modifying ‘compounds of the foregoing aspects, inching any embodiments or combination of embodiments threof, asset forth above in the manufacture ofan ingest- ible composition to reduce the htteness ofthe ingstible 10094] The disclosure also provides methods that core- spond to each ofthe foregoing uses. Thus, in certain elated aspects, the disclosure provides methods of enhancing the sweetness of an ingestible composition, comprising intr: ducing an amount such asa sweeiness-enbancing ellective mount) of any Havor-modifying compounds of foregoing fspocts,inciiding any embodiments ‘or combination of embodiments thereof, as set forth above, to the ingestible composition. In some other related aspects, the disclosure provides methods of reducing the sourness ofan ingesible ‘composition, comprising intrducing an amount (such as @ soumess-relucing effective amount) of any Mavor-modi ing compounds of foregoing aspects, including any embodi- ricns oF combination of embodiments there, as st forth above, 1 the ingestible composition In some other related fspocts, the disclosure provides methods of reducing the binemess of an ingestible competion, comprising inro- ducing an amount (such as a biterness-reducing effective amount) of any favor-modifying compounds of foregoing pects, including any embodiments or combination of tmbodiments thereof, as set forth above, tothe ingestible composition 10095] The foregoing uses and methods generally involve the use of the flavoremodifying componnds in composition containing one oF more additional ingredients For example, Jina last one aspect, the disclosure provides compositions comprising ay flvormoditying compounds of the forego= ing aspects, including any embodiments or combination of embodiments there, asset Tort above, wherein the Mavor- ‘modifying compounds make up atleast SO% by weight of the compositions on a dry weight basis (eg. based on the total weight of the composition excluding the weight of any a solid-state compositions comprising any favor-modi Compounds of the forepoing espe inciaing any embod ‘ments of combination of embodiments there, as st forth wherein the favor modifying compounds make up at 50% by weight of the solid-state compositions, based ‘onthe total weight of composition. In another related aspect, the disclosure provides ingestible compositions comprisingUS 2022/0304348 AL Aavor-modifying, compounds of the foregoing aspects, including any embodiments or combination of embodiments thereof, as set forth above, wherein the concentration of the ‘lavor-modifying compounds in the ingestible compositions fis no more than 200 ppm. In another related aspect, the dlislosure provides ingestible compositions comprising any favor-modifying. compounds of the foregoing aspects, ‘ncluding any embodiments oF combination of embodiments thereof, as set Forth above, wherein the ingestble composi- jons comprise a calorie sweetener, suchas suerse, fructose, Avlitol, etythstol, or combinations therwot. In another ‘elated aspoc, the disclosure providers concentrated sweet- ning composition comprising any Asvorsmodifying com pounds ofthe foregoing aspects, inluding any embodiments ‘or combination of embodiments thereof, asset Forth above, and sweetence 10096] -Incerin embodiments oF any aspeets and embodi- ‘ments se fot herein that refer to an ingestible composition, the ingesible composition is non-naturlly-occuering product, such 2s a composition specifically manufactured for the production ef a flavored product, such as food or beverage product 10097] In generat, compounds as disclosed and described herein, individually or in combination, canbe provid in a composition, such 28 an ingestible composition. tn one embodiment, compounds as disclosed and desribed herein, individually oa combination, a impart a more sugae-lke ‘temporal profile or favor profile oa sweetener composition by combining one or more of the compounds as dislosed tnd described herein with one or more sweetners in the ‘woetener composition. In another embadiment, compounds as disclosed and described herein, individually or in com bination, ean inerease or enhance the sweet taste of ‘composition by contacting the composition thereof with the compounds as disclosed and described herein to form a ‘modified composition [0098] Thus, ia some embodiments, the compositions set Toth in any ofthe foregoing aspects (including in any uses for methods), comprise a favor-modifying compound and a ‘sweetener. In some embodiments, the composition further ‘comprises a vehicle. In some embodiments, the vehicle is water. In some embodiments, the flavorsmodifying cone pound s present at a eoncenteation at ar below ils sweetness recognition threshold [0099] For example, in some embodiments, the sweetener fs pretent i an amount from about 0.1% to about 12% by ‘weight In some embodiments the swoctencr x preset in at mount from about 0.2% to about 10% by weight. In some fbodimens, the sweetener is present in an amount from about 0.3% to about 8% by weight. In some embodiments, the sweetener is present jn an amount from about 0.9% 10 about 6% by weight, In some embodiments, the sweetener is reveal in an amount om about 0.5% to about 5% by ‘Weight In some embeidiments the swceteners preset inant amount from about 1% 10 about 2% by weight. In some tmbodimens, the sicetner is present in an amount from about 0.1% t0 about 5% by weigh. In some embodiments, the sweetener is present in an amount from about 0.196 10 about 4% by weight In some embodiments, the sweetener is present in an amount rom about 0.1% to about 3% by ‘weight Insome embodiments the sweeteners preset in at fsmount from about 0.1% to about 2% by weight, In some fmmbodiments, the sector is present in an amount from about 0.1% t0 about 1% by weight. In some embodiments, Sep. 29, 2022 the sweetener is present in an amount from about 0.1% 19 about 0.5% by weight. In some embodiments, the sweetener js present in an amount from about 0.5% to about 10% by ‘weight In some embodiments, the sweeteners present in an mount from about 2% to about 8% by weight In some further embodiments of the embodiments set fonh inthis paragraph, the sweetener is sucrose, fructose, glucose, xy tol, erythtol, or combinations thereof. {10100} In some other embodiments, the sweetener is pros ent in_an amount from 10-ppm t> 1000 ppm. In some ‘embodiments, the sweeteners present inn amount fom 20 Ph to 800 ppm. In some embodiments, the sweetener is present in an amount from 30 ppm 10 600 ppm. In some tmibodimens, the swectencris present inn amount fom 40 pm to 500 ppm. In some embodiments, the swectencr is present in an amount from 0 ppm to 400 ppm. In some fmbodimens, the sweeteners present nan amount fom 50 ‘hm to 300 ppm. In some embodiment, the sweetener is present in a anount from 50 pp +0 200 ppm. Ta some ‘embodiments the sweeteners present in an amount fom $0 pm to 150 ppm. In some further embodiments of the embodiments st fort in this pargroph, the sweetener is a steviol glycoside, a mogrosie, a derivative of ether of the oregoing such as glycoside derivatives (eg, glucosyates), or any combination thereof {0101} The compositions ean include any suitable sweet ‘ners or combination of sweeteners. In some embodiments, the sweetener is common saccharide swoeteners, such 38 suenost, fucose, glucose, and sweetener compositions comprising natural sugars, such as corn syrup (nel high fructose cor syrup) oF other syrups or sweetener concentrates derived” trom naral uit and. vegetable sources. In some embodiments, the sweetener is sucrose, fractose, or a combination theteo. In some embodiments, the sweetener is sucrose. In some other embodiments Ihe sweetener i selected from rare natural sugars inelud Daallose, D-psicose, Lsibose, Daagatse, L-glveose L-f- cose, Learhinose, D-uranose, ad D-leverose, Ia some tembdiments, te sweetener is selected from semi-syathetic “augar alobol” sweeteners such as erthritl, jsomalt, ae- titol, mannitol, sorbitol, xylitol, maltodextrin, and the ike In some embodiments, the sweetener is selected fom art ficial sweeteners such as aspartame, saeharin, agesuliame- K, cyclamate, sucrose, andalitame. In some embodiments, the sweetener is selected from the group consisting of eyelamic acid, mogrosde, tapatose, maltose, palatose, rumnose, sucrose, fructose, lactose, neolame apd other aspartame derivatives, glucose, Detryptophin, glycine, tmalitol, lstitol, isomalt, hydrogenated. ghicose syrup (HGS), hydrogenated sarc hydrolyzate (HSH, stevioside, rebaudioside A, other sweet Stevia-hased glycosides, chemi- cally modified steviol glycosides (such as. plucosylted steviol glycosides), mogrosides, chemically modified rmoprosides (such a6 glucosylated mogrosides), carrelame tnd other guanidine-based sweeteners. In some embodi- ‘ments, the sweetener isa combination of two or more ofthe sweeteners set forth in this paragraph. In some embod tents the sweetener may combinations of two, thre, four or five sweeteners as disclosed herein, In some embodi- ‘ments, the sweetener may be sugar In some embodiments, the sweetener may be a combination of one or more sugars nd other natural and arficial swectenrs. In some embodi- rmenls, the sweetener isa sugar. Ia some embodiments, the ‘sugar is cane sugar. In seme embodiments, the sugar is bootUS 2022/0304348 AL sugar In some embodiments, the sugar may be suerose, fructose, glucose or combinations thereof In some embodi- sens, the sugar may be sucrose, In some embodiments, the ‘gar may he a combination of Irictose and glucose [0102] The sweetener can also include, for example, sweetener comporitons comprising one or more natural oF symthotic carbabydrat, such as corm syrup, high Inecose cor syrup, high maltose eam syrup, glacose syrup, sural ‘ose syrup, hydrogenated ghucose syrup (HGS), hydeoge: nated starch hydrolyzate (FISH, or ober syrups ar sweet fener concentrates derived from natural frit and vegetable sourees, or semi-eyntbete “sugar alcohol” sweeteners such as polyols. Non-limiting examples of polyols in some embodiments include erythiol, maltitol, mannitol, sorbitel, Iacttl,xylital,isomalt propylene glycol, elycerl (glye- in), treitol, galatitl,palatnose, reduced somali osaccharides, reduced xylo-ligosaccharides, reduced gen Uovligostocharides, reduced maltose syrup, redieed ilvcose syrup, isomaltose, maltodextrin, and the like, and Sugar alcohols or any other carbohydrates or combinations thereof capuble of being reduced which do not adversely alec taste [0103] The sweetener may be a matural or symthetie set. ener that includes, but is aot limited to, agave inn ave ‘agave syrup, amavake, brazzein, brown rice syrup, coconut crystals, coconut sugars, coconbt syrup, date sugar fractans (aso reiered to a inulin fiber, fruto-oligosaccha- rides, or oligofructose), preen stevia powder, stevia rebau- diana, rebaudioside A, rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside F, rebaudioside F, rebauion fide I, rebandioside H, rebaudioside L, rebaidioside K, rebaudioside J, rchudioside N, rebatdioside O, reba stevioside extracts, honey, Jerusalem artichoke syrup, ico fice root, fue han guo (iit, powder, oF exacts), hucuma (init, powder, or extracts), maple sap including, for ‘exanple, sp extracted from Acee Saccharum, leer migra, ‘Aoer rubrum, Acer saccharinun, Acer platanaides, Acer inegundo, Acer macrophylium, Acer grandidentatin, Acer ‘labrum, Acer mono), maple syrup, maple sugar, walt sap (including, for example, sap extracted ftom Juglans cinerea, uglans nigra, Juglans ailaiola, Juglans regia) birch sp (Gneluding, for example, sap extracted from Betula papyrif era, Betula alleghaniensis, Bemla lent, Betula migra Betula populifolia, Betula pendula, syeamore sap (such as, for example, sap extracted from Plavanus occidentalis), ironwood sap (such 3s, for example, sap extracted from Oserya virginiana), mascobade, molasses (such as, for ‘example, Blckstrap molasses), molasses sugar, monatin, rmonelin, cane sugar (also referred to as natura sug unrefined eane sugar, or sverose), pal sugar, panocha, piloneillo, padura, raw sugar, rice syrup, sorghum, so hum syrup, cassava syrup (also referred to as tapioca ‘ynup) thaumati, yacon oo, mal up, barley mall syrup, barley malt powder. beet sugar, cane sugar, crystalline juice crystals, caramel, carbtel, carob syrup, castor sugar, hydro- ‘enated starch hydrates, hydrolyzed ean juice, hydrolyzed Starch, invert sugar, anethole, arabinogalacian, arrope, syrup, P4000, acesulfame potassium (also referred 0 as acesulfame K orace-K),alitame (also referred to as alae), fadvaniame, aspartame, buiyunoside, neotame, benzamide derivatives, bemadame, candere,carelame and other gua nidine-based sweeteners, vepotable fiber, com sugar, cou- pling sugars, cureuli, eyclamates,eyclocaroside I, demee Sep. 29, 2022 ara, dextran, dextin, distatie malt, dulcin, sverol, valzn, Auleoside A, duleosie B, emul saccharin, estragole, etbyl maltol, glucin, pluconic acid, lucone-lactone, glicosamine, glucoronie acid, glycerol, lyein, glyeyphilln,elyeyrhizin, glycyreetic acid mono: plucuroaide, golden sugar, yellow sugar. golden syrup, franulated sugar, ynostemma, hernandlein, isomerized Tiguid sugars, jallab, chicory oot dietary fiber, Kynurenine derivatives (inchading "N-formyl-kynurenine, N-acetyl- kymurenine, 6-chloro-kymurenine), galactitol,Hitesse, li cine, yeasin, lgduname, guanidine, falemum, mabinin I, raabinlis IL, maltol, makisors, maltodextrin, malowiol, ‘mannossmine, mireculin, mizuame, mogrosides (nchiding, for example, mogroside TV, mogroside V, and neomogr side), mukuroioside, nano sugar, naringin dihydroctaleane, reohesperidine dihydrochalcone, nib sugar, nigero-olio- saccharide, norbu, ongeat syrup, osladin, pekmez, pentadin, periandrin I, perlaldehyd, perilartine, peiphyllum, phe- nylalanine, “phlomisoside I. phlorodizn, phyllodulin, Polyglyeitol syrups, polypodoside A, picrocaryoside A, Plerocaryoside B,reblams, refiners syrup, rub syaup, rubs foside, solligueain A, siamonoside I, sitiia geosvenori, soybean oligosaccharide, Spends, SRI oxime Y, steviol lyeoside, steviolbioside,stevioside,strogins 1, 2, and 4, Sucronie aed, suerononat, sugar, susan, phloridzin, super: aspartame, tetrasccharde, thretol, treacle, trlobatin, ‘ryptophan and derivatives (6-tflucromethy|-rypophan, Gechlore-Detrypiophan), vanilla sugar. volemitol, itch symp, aspartame-acesuifime, asugrin,aromedendin-3-0- acetate, dihydotamarixain-3-O-aetate, and combinations or blends of any two or more thereo In stl other embodi- ments, the sweetener can be a chemically of enzymatically ‘modified natural high poteney sweetener. Modified natural high potency sweeteners include glycosylated natural high poteney sweetener such as glucosy- galactosy- or facto- f+ derivatives containing 1-50 glycoside residues. Glyeo- ‘lated natural high poteney sweeteners may be prepared by enzymatic tansglycosyltion rection catalyzed by various enzymes possessing transglyeosylating activity. Th. some embodiments, the modified sweetener can be substituted or ‘unsubstituted. 10104] Additional sweeteners also include combinations ‘ofany two oF more of any othe aforementioned sweeteners Tn scine embodiments, the sweetener may comprise combi- nations of two, three, four or five sweeteners as dislosed heroin. ln some embodiments, the sweetener may be a supa. Insome embodiments, the swectener may be a combination of one or more sugars and other natural and artificial sweeteners, In some embodiments, the sweetener is caloric sweetener, seh as sucrose, fctose, xylitol, eryhrtel, oF combinations threo. In some embdiments, the ingestible ‘compositions ae free (or, in some embodiments) substan fice of steviaderived sweeteners, such as stevil lyeosides, glucosyated steviol glycosides, or rebaudi- Sides. For example, in some embodiments, the ingestible compositions are ether fre of sevia-erived sweeteners or onprise slevi-derived sweetener in a concentation of 0 ‘more than 1000 ppm, or no more than S00 ppm, oF no more than 200 ppm, or no more than 100 ppm, or no more than $0 Phi, of no more than 20 ppm or no more than 10 ppm, oF hho more than S ppm, orno more than 3 ppm or no more than ppm. 10105] The favor-modifying compounds ean be present in the ingestible compositions in any suitable amount In someUS 2022/0304348 AL embodiments, the favor-modifying compounds are present inn amount suficient wo enbanee te taste (eg, enbsnce the sweetness, reduce the stimess, of reduce the biternes) of the compositions, Thus, in some embodiments, the ingest ‘ble composition comprises the favor modifying compound in a concentration no greater than 200 ppm, or no greater ‘han 150 ppm, oF no greater than 100 ppm, oF no greater than 50 ppm, or no greater than 40 ppm, or no greater than 30 Ppp, oF no greater than 20 ppm. In some embodiments, the Navoemodilying compound. is present ina minimum mount, such as 1 ppm or $ ppm. Thus, in some embod mens, the ingestible composition comprises the flavor ‘modifying compound ina concentration ranging fom | ppm ‘© 200 ppm, o from 1 ppm to 130 ppm, of from 1 ppm to 100 pp, or fm I ppt 50 ppm, or from I ppm wo 4D ppm, or from 1 ppat © 30 ppm, or from 1 ppm 0 20 ppm, br from $ ppm to 200 ppm. or from 5 ppm to 150 ppm, oF trom 5 ppm to 100 ppm oF from 5 ppm to 90 ppm, or from 5 ppm to 80 ppm, of from 5 ppm to 70 ppm of from § ppm ‘© 60 ppm, of from 5 ppm wo 50 ppm, oF fom 5 ppm to 40 pm, or from 5 ppa to 30 ppa, or fom 5 ppm 20 pp. In embodiments whore a sweetener, such 8 Sucrose OF Iractose are preset, the weight -to-weight ratio of sweetener ‘othe favor-niodifying compound in the ingstble compo- sition ranges from 1000-1 to $0000-1, or from 1000: 10 100001, oF frm 2000: to $0001 10106] ‘The fvor-modifying compounds can be combined ‘nay suitable way. For example, in some embodiments, the ingesible composition ar swectener concentate contains @ single flavoremodifying compound ofthe embodiments set forth above, such as any one of the compounds identfiod above as Compound 101, Ci 102, Compound 108, Compound 10, Compound 105, Compound 105, Com pound 107, Compound 108, Compound 109, Compound 110, Compound 111, or Compound 112. In some other cmbodiments, the ingestible composition or sweetener com tentrate contains mixtures of two or more favor modifying ‘compounds of the embodiments set forth above, Limiting examples of such mixture ined a mixture of Compound 109 sind Compound 110. Such mixtures ean include 160 oF ‘ore flavor-modifying compounds ofthe embodiments set Toth above ia aay suitable rao, For example, in embodi- ments where the ingestible composition or sweetener con centrate contains « mixture of Compound 109 and Con pound 110, the two compounds can be preseat in any Suitable ratio relative to each other, such as wi ratio fanging fom 1:10 0 10:1, oF Ft 5:1, oF fom 1:3 10 3:1 ‘The ingestible compositions or sweetener concentate, it cerain embodiments, also comprise any ational ingredi- ens or combination of ingredients as are commonly used in ood and boverage prods including, but aot limited to [0107] acids, including, for example citric acid, phos phoric acid, ascorbic acid, sodium acid sulfate lactic aid, or tartaric acid, [0108] bitter ingrediats, including. for example eafeine, quinine, green te, catechins, polyphenols, green robusta coffee extract, green colfee extract, potassium chloride, menthol, or proteins (uel as proteins and protein isolates derived ftom plants, algae, or fungi): [0109], coloring agents, including, for example caramel color, Red 40, Yellow iS, Yellow #6, Blue P, Red 13, purple carot, black carrot juice, purple sweet pollo, veg” ‘able juice fut juice bei carotene, tuner curcumin, oF niu dioxide; Sep. 29, 2022 [0110] preservatives, including, for example sodium ben- ~zoate, potassium benzoate, potassium sorbate, sodium meta- bisullte, sorbic acid, or benzoic acids 10111] antioxidants including, for example ascorbic acid, calcium disodium EDTA, alpha tocopherols, mixed tocoph fers, rosemary extret, grape seed extice, resveratrol OF sodium hexametaphosphate: 0112] vitamins or functional ingredicats including, for example resveratrol, Co-Q0, omeza 3 fatty acids, theanine, choline chloride (itocotine),fbersol, inolin (chicory root), taurine, panax ginseng extrc guanana extrac, ginger extract, Lsphenylalanin, L-camitine, L-tartrate, D>zlveoe- ‘onolaeione, inositol, biollavonoid, Echinacea, ginko biloba, Yerba mate, flax seed oil, parcnia cambogia rind extract, White tea extract, ribose, milk thistle extract, grape seed extract pyrodixine HCI (vitamin BO), eyanoobalamin (¥ita- ‘min B12), niscinamide (vitamin BS), biotin, calcium lactate, calcium pantothenate (paneihenie acid), calcium phosphate calcium carbonate, chromium chloride, chromium polyni- cotinste, cup sUlfte, folie acd, ferric pytophoxphate, jroo, magnesium lactate, magsesium carbonate, magnesium sulfite, monopotassinm phosphate, monosodium phosphate, phosptors, potassium todide, potassium phosphate, ribo: avin, sodium suet, sodium gluconate, sodium polyps: phate, sodium bicarbonate, thiamine mononitate, vitamin 13, vitamin A palmitate, zine guconste, zine latte, or zine sulphate, [0113] clouding agents, including, for example ester gun, brominated vegetable oil (BYO) oF sucrose acetate isobu tyre (SAIB); 0114] butfers, including, for example sodium citrate, Potassium citrate, oF salt [0115] flavors, including, for example propylene glycol, eiliyl alcohol, glycerine, yum Arabic (gum acacia), malto~ dextrin, modified cornstarch, dextrose, natural or, nat fal favor with other natural flavors (natural flavor WONE), ‘natural and anifcial Havas, artificial favor, silicon dioxide, ‘magnesium carbonate, or Wicaleium phosphate; of [0116] starches and stabilizers, including. for example pectin, xanthan gum, carboxylmethyleellalose (CMC), pol orbate 60, polysorbate 80, medium chain triglycerides, cellulose gel cellulose gum, sodium exscinate, modified food starch, gum Arabic (gum acacia), inulin, o carr een. [0117] The ingestible compositions or sweetener concen: teats can have any suitable pH. In some embodiments, the flavor-modifying compounds enbinoe the sweetness of a sweetener under abroad range of pl, eg from lower pi 19 neutral pH. The lower and neutral pH includes, but is not ited to, a pH from about 2 to about 8.5; fom about 3.0 to about 80 from about 3.5 about 7 5:and from about 40 1o about 7. In certain embodiments, compounds as disclose and described herein, individually or in combination, can enhance the perceived swectness ofa fixed concentmtion of ‘woetener in taste tess at a compound concentration of bout 50M, 40 iM, 30 4M, 20 iM, of 10 1M at both law to neu pli value. In certain embodiments, the enhance- ‘ment faci of the componnds as disclosed and describe herein, individually or in combination, a the lower pH is substantially similar to the eshancemeat factor of the com- pounds at neutral pil. Such consistent swoet enhancing property under # bread range of pH allow a broad use in aUS 2022/0304348 AL wide variety of foods and beverages of the compounds as Aislosed and described herein, individually oF in combina [0118] ‘The ingestible compositions set forth according to ny of the foregoing embodiments also incude, in eentain fmbediments, one of more additional Aavormodifying ‘compounds, such as compounds thst enhance sweetness (eg, besperetin, naringenin, glucosylated steviol glyeo- sides, ele), compounds that block bitterness, compounds that enhance umami, compounds that reduce sourness or licorice taste, compounds that enhance saltiness, compounds that enfance a cooling eee, or any combinations of the oregoing. Plavored Products and Concentrates [0119] In contain aspoots, the disclosure provides Navored routs comprising any composition ofthe preceding five fspects, In some embodiment, the Tavored products are beverage products, suchas soda, Davored water, te, and the like, In some other embodiments, the Bavored products are {ood products, such as yogurt [0120] Ia embodiments where the Mavored product is a beverage, the beverage may be selected from the group consisting of eahapeed sparkling beverages, coas, lemon Time favored spukling beverages, orange favored sparking beverages, grape favored sparkling beverages, strawberry flavored sparkling beverages, pineapple favored sparking beverages, ginger-ales, root boors, fui juces, ritavored juice, juice drinks, nectars, vegetable juices, vegetble- Favored juices, sports drinks, energy drinks, eabanced water drinks, enhanced water with vitamins, near water drinks, coconut water. tea type drinks, coflees, cocoa drinks, beverages containing milk components, beverages contain ing cereal extracts and smoothies. In some embodiments, the beverage may be a soft drink [0121] Incertsin embodiments of any sspocts and embod ‘ments set font herein that refer an flavored proc, the ‘avored predict is @ noa-naturlly-occutrng peoduet, sch ‘8 4 packaged food or beverage product. [0122] Further non-limiting examples of food and bever- age products oF formulations inchode sweet coatings, frost- ings or ples for sueh products or any entity included inthe Soup category, the Dried Processed Food category, the Beverage category, the Ready Meal category, the Canned or Preserved Food category, the Frozen Processed Food cat gory. the Chilled Processed Food category the Snack Food fategory, the Baked. Goods category, the Confectionery fategory, the Dairy Preduct category, the Tee Cream cat ‘evory, the Meal Replacement eatepory the Pasta and Noodle category and the Sauees, Dressings, Condiments category, the Baby Food category, andor the Spreads category. [0123] In general, the Soup extepory refers to canned’ preserved, dehydrated, instant, chilled, UHT and. frozen Soup. Forte purpose of this definition soup(s) means food prepared from meat, pouty. fish, vegetables, prains, fut fn other ingodients, cooked ina igo which may clade Visible pieces of some oral ofthese ingredients. t may be clear (asa broth) o thick (as chowder), smooth, pureed or ‘honky, redyto-serve, semi-condensed or condensed and ‘may’ be served hot of cold, a fist course ora the main course of a meal or as.a beoween meal snack (sipped ike a beverage). Soup may be used at an ingredient fr preparing other meal components and may range fom bros (con Ssommé) 1 sauoes (ream or choese-based soups) Sep. 29, 2022 {0124} The Detydrated and Culinary Food Category ws ally means") Cooking aid products soch a: powders, trials, pastes, concentrated liquid procs, including Concentrated bel, boll nd blank prot a presied cubes, lots or powder or gana ona, which Dr sold separately axa finshed proviet ora an ingredient within a produc, sauces and recipe mines (tepals of technology) (3) Meal solutions produits sich a dehy dated and feeze dried oops, isting dehyde soup mies, dehydrated instant soups, dehydrated read-to-cook Soups, dehydrate or ambient preparations of ready-made ines, mals and single serve cneos ncinding pasta, potuto and rice dishes, and (ii) Meal embellishment pr tes such a condiment; mainades, saa desing salad toppings, dips readin, ater mise, sel sable spreads, Barbecsatesfiqid espe ines concentrates, sees oF sauee mines, ieloing reeipe mixes for sala, sok ss a finished) prodoet or as an ingredient Within a product, weer det, tigi oe zen 10125] ‘The Beverage category usually means beveges, beverage mixes and consents, inching bit aot nied to carbonate al non-carbonstel Beverages alcbolie ant tons alcobic beverage, ey Io drink Beverages, Hid concent formulations for preparing beverages such #8 Sodas, and dry powdered beverage precursor axes. The Beverage category also includes the’ alcohol dias, the softs, sports inks, tonic beverages, and hot dik The alcool drinks incloe, bu are ot lined to box. cilcjpeny FAB, wine and spirits. The sof drinks ace, bt are not mite to carbonates, uch as cols and non-ola carbonates: fit juice, such as juice, nectar, jue drinks and nit Navored drinks; boted water, which includes Sparkling water sping wate ad portable Water, Ke= onal drinks, which can he carbonate oe sl an clade sport, ene’ oe elise drinks: conceattes, sch a id and powder concentrates in ead to drink measure. The his, ether hot or col, inte, but are not Tinted 1 coffe or ie coffee, such afresh instant, and combine tev orice a, sch ss lack, geen, white oolong. ad favored tea: and ier diaks including Tao male 07 plantbased posers, pranules, blocks or bles mixed With hk o water 0126] The Snack Food category yenerlly refers to any food that ca be light informal mal Sncaing. bot not limited to Sweet and. savery stacks and. stack bar. Examples of snack ood ac, bt are not limited oi snacks, chipslrisps, exteded snacks, ortll‘cor chips, peopeorm, prevels, nis and ather sweet and savory snack. amples of snack bars igelude, but ae sot linited trols ars, reaklst har, enor bar, rit brs Sn tee snack ars [0127] The Baked Goods category zencaly refers waxy tile product the prs of preparing Which svolves exposure to hext or excesive sight. Fxarmples of ake onde inlods, but are nat mite to Bread, buts, cooks, Iu, cereal, toaster pasties, pastes, wales, tris, biscuit, pes, egestas, quiches, cake any baked fds, and a ombinaton there 10128] The fee Cream category generally refers to frozen dessert containing ream and sar and favoring. Fxamples oF fee cream ilide, Butte 8 Hite to pulse fee ream take-home ice cca fozen yoghurt aod artisanal see creas, ot bean ro bean and mung bean) and Fic-based ie erasUS 2022/0304348 AL [0129] The Confectionery category generally refers to ‘edible product that is sweet to the taste, Examples of ‘confectionery include, but are not limited to canis, gel in, chocolate confectionery, sugar confectionery, gum, and the lies and eny combination product 10130] "The Meal Replacement category gencrlly refers to ny food intended to replace the normal meals, particularly Tor people having health or fitness concerns. Examples of ‘meal replacement include, but are not limited to slimming products and convalescence products. [0131] The Ready Meal category generally refers to any food that can be served as meal without extensive prepara tion or processing. The reedy meal includes prodcts that have had recipe “skills” adda to them by the manufacturer, resulting in 4 high degree of readiness, completion and soavenience, Exaniples of ready meal include, But sre act limited 19 canned/preserved, frozen, dred, chilled ready meals; dinner mixes; frozen pizza; chilled pizza; and pec pred salads, [0132] The Pasta and Noodle category includes any pastas sandr aoodles including, but act limited to canned, dred ‘and chilled fresh past; and plain, instant, chilled, frozen and sack noodles, [0133] The Canned! Preserved Pood category includes, but Js not limited w canned preserved meat and meat products, fishsoafood, vegetable, tomatoes, beans, fut ready meals, soup, pista, and other eannedpreserva fons [0134] The Frozen Processed Food category includes, but Js not limited to frozen processed red meat, processed poulUy, processed fish/seafood, processed vegetables, meat Substtes, processed potatoes, bakery products, dessers, ready meals, piza, soup, noodies, and viber frozen food. [0135]. The Dried Processed Food category’ includes, buts ‘ot limited to roe, dessert mixes, dried ready meals, dehy rated soup, instant soup, dried pasta, pain noodles, and fnstint noodles. The Chill Processed Tood category includes, but is not limited to chilled processed. meats, processod fish/scafood products, lunch kis, fresh cut fruits, ready meals, pi7za, prepared salads, soup, fresh pasta and ‘ocd. [0136] "The Sauces, Dressings and Condiments category includes, bu isnot limited to tomato pastes and purees, ouillonstock cubes, herbs and spices, monosodium gluta mate (MSG), lable saves, soy bisa sees, pasta SAUCES, wevevoking savees, dry ‘swuoewpowder mixes, Ketchup, ‘mayonnaise, mustard, salad dressings, Vinwigrtes, dips, Pickled products, and other sauces, dressings and condi- [0137] The Baby Food eateyory includes, but i not lim sted to milk- or soyhean-based formula: and prepared, ded and other baby food, [0138] The Spreads category includes, buts not Kmite to jams and preserves, honey, chocolate spreads, nut based spreads, and yeast ased spreads. [0139] The Dairy Prodct category generally refers to tdible product produced from marumal's milk. Examples of| ‘liry product inchude, but are not limited to drinking mill products, cheese, yoghurt and sour milk drinks, and ether {airy products [0140] -Addivionsl examples for Bavored products, ption- Jaely food and beverage products or formulations, re pr: vided as follows. Excmplary”ingestible compositions include one of more canfectioneres, chocolate confection ery, tablets, countines, bagged sellinessoflines, boxed Sep. 29, 2022 sssortments, standard boxed assortments, vist wrapped Iiniatures, seasonal chocolate, chocolate with toys, all jores, other chocolate confectionery, mins, standard mints, power mints, boiled sweets, pastilles, gums, jellies and chews, toffee, caramels and nougat, macated eonfeetion- ey, lellipaps, liquorice, other sugar eonieetionery, bread, packagedindusrial bread, unpackagearisanal brea, pas tres, cakes, pekaged/industrial cakes, unpackaged/artisaal cakes, cookies, chocolate ested biscuits, sandwich bis, filled biscuits, savory biscuits and crackers, bread substi- tutes breakfost cecal, re cereals, family breakfast cereals, Fakes, mel, other cereals, children’s breakfast cereal, hot corals, ice cream, impulse ice eream, single portion dairy jee cream, single portion water iee cream, mult-pack day fee eran, mulicpack water icecream, take-home icecream, take-home dairy iee cream, ice eam dessens, bulk ice cream, iake-home water icecream, frozen yoghurt artseal Jee cream, dairy products, mil, reshipasteurized milk, fall Fat fresh/pasteunzed milk, semi skimmed fresh/pasteurized rik, Fongfife/uht milk, fall fat Tong Tife/uht milk, semi skimmed Tong fifeluht mik, fat-free kang Tift mil, goat nik, condensedievsported milk, plain condensed/evipo- rated milk, Navored, fictional and other condensed alk, flavored milk drinks, diry only favored milk drinks, Dae vored milk drinks with fruit juice, soy milk, sour milk drinks, fermented dairy drinks, coffee whiter, powder nil, flavored powder milk drinks, cream, cheese, processed cheese, spreadable processed cheese, unspreadable pro- tested cheese, unprocessed cheese, spreadable unprocessed cheese, hard cheese, packaged bard cheese, unpackaged hard cheese, yoghurt, plaininatural yoghurt, Mavored yoghurt, fiuted “yoghurt, probiotic yoghurt, drinking Yoghurt regular drinking yoghurt, probiotic. drinking Yoghurt, chilled and shelfstable desserts, dairy-based dos forts, soy-based dossers, chilled snacks, fromage Tras and quark, plan fromage frais and quark, favored fromage fais and quark, savory fromage rasan quark, sveet and savory snacks, frit snoeks, chipslrisps, extruded snacks, orl’ com chips, popcom, pres, nul, other sweet and savory snacks, snack bars, granola bars, breakfast bars, encrzy bars, Frat hars, other snack bars, mal replacement products, slimming’ products, convalescence drinks, ready meals, anne ready meals, frozen ready meas, dred ready meals, chilled rexdy meals, dinner mixes, Irozen pizza, chilled pizza, soup, canned soup, dehydrated soup, instant soup, hulled soup, hot soup, frozen soup, pasta, canned past, dried pasta, chilled fresh pasta, noodles, plain noodles, instant noodles, cupsthow instant noodles, pouch instant oodles, chilled noodles, snuck noodles, canned food, ‘anne meat and meat produts, canned fish/safood, canned vegetables, canned tomatoes, canned beans, canned fit, canned ready meals, canned soup, canned pasta, other tzanned foods, frozen Tood, frozen processed red meat, frozen processed. poultry, frozen processed. tish/seafvod, frozen processed vegetables, frozen meat substitutes, frozen potatoes, oven baked potato chips, other oven baked potato prelucs,non-oven frozen potatoes, frozen bakery products, frozen desserts, trozen ready meals, frozen pi77a, frozen soup, frozen noodles, other frozen Tood, dried food, dessert mixes, dried ready meals, dehydrated soup, instant soup, dried posta, plain oodles, instant noodles, cups/bow instant noodles, pouch instant noodles, chilled Tood, chilled pro- cested micas, chilled fshiscafood prodvcts, chilled pro- fess fish, chilled coated fish, chilled smoked fish, chilledUS 2022/0304348 AL 18 lunch Kit, chilled ready meal, chilled pizz, chilled soup, chilledesh past, chilled noodles, ois and fats, olive ol, vegetable and seed oil, cooking Tas, butler, margarine, prendable oils and fats, fnctional spreadable ols and fas, sauces, dressings and condimons, tomato pastes and purces, bouillostock cubes, stock cues, gravy granules, liuid stocks and fonds, hers and spices, fermented sauces, soy based sacs, pasta sauces, wet stoes, dry sauces/powder mixes, ketchup, mayonnaise, regular mayonnaise, mustard, salad dressings, regular sla dressings, low ft salad dress ings, vinaigretes, dips, pickled products, her sauces, dressings and condiments, baby food, mil formula, stan- dda milk formila, follow-on mille fomnla, toddler mill Foemula, hyposllenenic milk formula, prepared baby food, Arid baby food, other baby food, spreads, jams and pre- serves, honey, chocolate spreals, nut-based spreads, and yeastbased spreads, Exemplary ingestible compositions also include confectioneies, bakery products, ice creams, dairy products, sweet and savory snacks, snack bars, meal replacement products, ready meas, soups, pastas, noodles, fanned foods frozen foods, dried foods, chilled fos, oils and fits, baby foods, of spreads or a mixture thereof Exemplary ingestible compositions also inelude breakfast cereals, sweet beverages oF solid or liquid concentrate ‘compositions. for preparing beverages, ideally $0.28 10 tenable the reduction in concentration of previously known saccharide sweeteners, or anificial sweeteners [0141] Some embodiments provide a chewable composi tion that may or may not be intended to be swallowed. In some embodiments, he chewable composition may be sum, chewing gum, sugarized gum, sugar-free gum, funtional tom, bubble gum ineluding componnds as disclosed and ‘describes herein, ividually or in combination [0142] Typically at least a sweet rovepior modulating ‘amount, a sweet ecepior ligand modulating amount, a sweet avor modulating smount,a sweet Mavoring agent sou, fa sweet favor enhancing amount o a therapeutically effce- ve amount of one oF more ofthe present compounds will be adkled to the ingestible composition, optionally in the presence of sweeteners 50 thatthe sweet lavor modified ngesible composition has an increased sweet taste as ‘compared tothe ingstible composition prepared without the compounds of the present invention, as judged by human beings or animals in general, or in the case of formulations testing, as judged by a majority of «panel of atleast eight Fnman tse tester, via procedures commonly known in the field [0143] In some embodiments, compounds as disclosed and deseribod herein, individually orn combination, modu- Tate the sweet taste or other taste properties of other natura or syathetie sweet tastanls, and ingestible compositions ‘made therefrom. In one embodiment, the compounds as disclosed and deseribed herein, individually or in combina tion, may be used or provided in its ligand eahancing concentation(s). For example, the compounds as disclosed and dascribed horein, individually or in combination, may be present in an amount of from 0.001 ppm 10 100 ppm, or rarrower alternative ranges from 0.1 pa so SO ppt, from 0.01 ppm to 40 ppm. from 0.05 ppm to 30 ppm, fom 0.01, pm fo 25 ppm, or from 0.1 ppm to 30 ppm, oF from 0.1 ppm {025 ppm, or from | ppim to 30 ppm, or fom 1 ppm to25 ri [0144] Ia some embodiments, favor-modifying com pounds as disclosed and dosribod herein, individually or in Sep. 29, 2022 combination, may be provided in a Mavoring conceatrate formulation, e., suitable for subsequent processing 10 produce a eady-foase (Le, ready-to-serve) product. By “a Aavoring concentrate formulation”, its meant a formulation which should be reconstiuted with one or more difuting medium fo become a ready-to-tse compesition, The tem “ready-to-use componition” is used herein interchangcably with “ingestible composition” whieh denotes any substance that, either alone of together with another substance, can be takea by mouth whether intended for consumption oF not. In fone embodiment, the ready-to-use composition inches a ‘composition that ean be direlly consumed by a human or fnimal. The flavoring concentrate formulation is typically used by mixing with or diluted by one or more diluting medium, eg. any consumable or ingestible ingredient or Prxluct, to impart or modily one oF more Mayors (© the diluting medium. Such a use process is often referred to as reconstitution. The reconsiition ean be conducted in a household seting or an industrial seting. For example, Jrozen fat juice concentrate can be reconstituted with water fr other aqueous medium by a consumer in a kitchen 19 obtain the ready-to-use fruit juice beverage. In another example, a soft drink syrup concentrate can be reconstituted swith water or other aquerts mem by a mannfactarr in large industrial scales to produce the ready-to-nse soft drinks. Since the flavoring concentrate formulation has the Favoring agent or favor modilying agent in # concentration higher than the ready-to-use’ composition, the Mavoring oncentate formulation is typically nat stable for being consumed direly without constitution. There are many benefits of using and producing a favoring conceatmte formulation. For example, one benefit is the reduetion in ‘weight and volume for transportation asthe favoring con cenfrate formulation can be reconstitued at the time of ‘usage by the addition of suitable solvent, solid or igi 10145] The favored products set Forth according 0 ay of the foregoing embadimens, also incl, in certsin embod rmenls, one or more kitonal fwor-modifving compounds, such as compounds that enhance sweetness (., hesperctin, haringenin, glucosylated.steviol glycosides, ete), com Pounds that block bitemess, compounds that eahanee “ums, compounds that reduce sourness,componnds that enhance saltiness, compounds that enhance a cooling elect, or any combinations ofthe orepoing 0146] Incertain embodiments of ay aspects snd embod sents sot forth herein that refer toa sweetening or Aavoring concentrate the swestening or Navoring concentrate is a ron-natraly-ooeurting product, such 282 composition sp cifically manufactured for the’ production of a favored luc, such as Food oe beverage prot, 10147] In one embodiment, the favoring eoncenteate foe ‘mulation ‘competes i) “compounds es disclosed and described herein, individually or in combination; i) 8 car Fier, and it) optionally at feast one adjuvant. The teem “carier” denotes a sully inactive accessory substance, such as solvents, binders, or other inert medium, which is ‘sed in combination withthe present compound and one or ‘more optional adjuvants. 10 form the formulation, For example, water or starch cin be a cartier for & Mavoring concentrate formulation. In some embodiments, the carrier js the same as the diluting medium for reconstituting the favoring, concentrate formulation; and in other embodUS 2022/0304348 AL 19. ‘ments, the cacrers diferent from the diluting medium, The ‘erm “earriet” as used herein inludes, but isnot limited to, ingestibly acceptable carier [0148] The term “adjuvant” denotes an additive which supplements, stabilizes, maintains, or enances the intended function or efectivencss oft ative ingredient, sch a the compound ofthe preseatinveaton. In one embodiment, the at Teast one adjuvant comprises one or more favoring ‘gents. The favoring agent may be of any flavor known 0 ‘one skilled in the aft oF constimers stch as the Haver of | chocolate coffee, tea, mocha, French vanilla, peanut butte, ‘hii, or combinations thereo. In another embodiment, the Jeast one adjuvant comprises one or more swecteners. The fone or more sweeteners can be any of the sweeteners ‘described inthis application In another embodiment, the at least one adjuvant comprises one or more. ingredients selected from the group consisting of emulsifier, Sabie Tizer an antimicrobial preservative, an antioxidant, vitamins, minerals, fats, starches, proven concentrates and isolates, salls, and combinations thereof. Examples of emulsifiers, Stabilizers, antimicrobial preservatives, antioxidants, vita ‘mins, minerals, fats, starches, protein concentrates and is lates, and salts are doseibod in US. Pat. No. 6.68.57, the content of which is hereby incorpeated by reference in its catty forall porposes [0149] Inne embociment, the present flavoring concen teate formulation ean be in form selected from the group consisting of liquid including solution and suspension, solid, oamy material, paste. gl, eream, and a combination thers, such asa liquid containing certain amount of solid contents. In one embodiment, the favoring, concentrate emulation isin form ofa Tguid inching aqueeus-based and nonagueous-based. In some embodiment, the present Tavoring concentrate formulation can be carkonsied oF non-carbonatd [0150] The favoring concentrate Formulation may further comprise a freezing point depressant, nucleating agent, or both as the atleast one adjuvant. The irezing point depres- sant if an ingestibly acceptable compound or agent which fa depress the freeing point ofa iguid or solvent to which the compound or agent is added. That isa Tguid or solution ‘containing ie freezing point depressant has lower freezing point than the gud oF solvent without the foezing point ‘depressant. In addition to depress the onset freezing point, the freezing point depressant may also lower the Water sctivity of the flavering concentrate formulation. The ‘examples of the freezing point depressant include, but are not limited to, carbohydrstts, ois, thy alcohol polyol eg lycoro, and combinations thereof. The nucleating, agent ‘denotes an ingesibly acceptable compound or agent which is able to facilitate nucleation. The presence of nucleating ‘agent in the Bavoring concentrate fomlation ean mmprove the mouthfeel ofthe frozen Blushes of a frozen sash and 10 help maintain the physical properties and performance ofthe slush ot frsering temperatires by increasing the number of Aesirable ie crystallization centers. Examples of nucleating agents include, but are not limited to, calcium silicate, faleium carbonate, titanium dioxide, and combinations thenot, [0151] Inge embodiment, the Ravoring concentrate foe- ‘ulation is formated to bave a low water activity for extended shelf life, Water activity isthe ratio ofthe vapor pressure of water in a formulation to the vapor pressure of ure water athe same temperature. In one embodiment, the Sep. 29, 2022 Aavoring concentrate formulation has a wate activity ofless than about O85. In another embodiment, the Mavoring concentate Formulation has a water activity of les than bout 80, In another embodiment, the favoring enncen- teat formation has a water activity of les han about 0.75 10152] In one embodiment, the favoring concentrate foe ‘lation hes the present enmpound in a concentration that js at least 2 times of the concentration ofthe compound in a realy-to-use composition. In one embodiment, the favor jing concentrate formulation has the present compound in concentration that i at lest 5 times of the eoneentration of the compound ina ready-to-use composition. In one embodiment, the favoring concentrate formulation has the present compound in concentration tat i at last 10 times Of the concentration of the compound in a ready-to-se Composition. In one embodiment, the flavoring concentrate formulation has the present compound in a concentration that iat eas 15 mes ofthe concenteation ofthe componnd in a ready-to-use composition. In one embodiment, the Flavoring concentrate formulation has the present compond ‘concentration that atleast 20 times ofthe concenra- tion of the compound in a ready-to-use composition. In one embodiment, the lavoring concentrate formulation has The present compound in a concentration that i at last 30 times ff the concentration of the compound ina ready-toase composition. In one embodiment, the flavoring concentrate ‘ormblation has the present compound in a concentration thats at east 40 times of the concentration ofthe compotnd jn a ready-to-use composition, In one embodiment, The flavoring concentrate formulation has the present compound fina concentration that sat last 50 times of the concentea- tion ofthe compound in a ready-to-use composition. In one embodiment, the flavoring concentrate formulation his The present compen in eoncenteatin tat i at least 60 times Of the concentration of the compound in a ready-to-use ‘composition. In one embdinent, the havering concentrate ormolation has the present compound in a concentration that i upto 100 times of the concentration of dae compotnd ina ready-to-use composition, 10153] The sweetening or favoring concentrates set forth sccording to any of the foregoing embodiments, aso Include, in cerain embodiment, one of more adalitional ‘avormodifying compounds, sch as compounds. that enhance sseeetness (ee, hespeetin, naringenin, glucosy Tate stevol glycosides, et), compounds that block bitter ness (eg. eriodictyol, homoeriodityo, sterubi, and sls or glyeoside derivatives thereof, as well as vanily ignans, fe, milairesinol and other compounds set forth in PC Publicstion No. WO 2012/146S84), compounds that enhance mami (e., rlbemamine, rabescensmine, (E)-3- (G.4-dimethoxypheny})-N-4-mesboxyphenethylaerylam- ‘Me, and the ike), compounds that rxluce sourness andor Ticorce taste, compounds that enkance saltiness, compounds that enhance a evoling elec, or any combinations of the foregoing. Methods of Preparation 10154] The compounds disclosed herein may be synihe- Sizwd by methods deseribed below, or by modification of these methods, Ways of modifying the methodology include, among others, temperature, solvent, reagents etc, known 19 those skilled in the art. In general, during any of the processes for preparation of the compounds lielosedUS 2022/0304348 AL herein, it may be necessary or desirable to protect sensitive br reactive groups on any ofthe molecules concerned. [0158] "In certain aspects, the disclosure provides metods tof making faver-modifying compounds of the foregoing fsspects via an enzyme-catalyaed process. For example, i ‘eriain embodiments, the methods include providing pre= cursor, such a elyeyehizin, ora derivative thereof. In some ‘embodiments, the plyeyehizn is symhesizd through enzy- Imatie procestes characteristic of those for enzymatically catyzed syntheses ofterpene compounds. The glyeyhizin fan be further desivatized in any suitable manner For fexample, in. some embodiments, the monoglucuronate Adrivative of glyeyrshirin ie synthesized by catalytically hydrolyzing the eter linkage between the two glacurony ‘moieties w remove the distal of the 880 moieties. Furher derivatives can be made, soch as sding an OF moiety at the positions identiied by R! and R® inthe compound of formula (1) or formula (a), by conventional synthetic EXAMPLES. [0156] To further ilustate this inveation, the following ‘amples ar included. The examples should not, of couse, be constracd specifically limiting the invention Var: tions ofthese examples within the senpe of the claims are within the purview of one skilled in the art and are consid- ered to fall within the scope ofthe invention 3s described, ‘and claimed herein. The reader will recognize that the shilled artisan, armed with the present disclosure, and skill fn the artis able to prepare and use the invention without exhatstive examples Example 1 ‘Sweetness Enancement [0157] A test compounds were tested for its sweetness enhancement of 58% (Wis) aqueous solution of sucrose. Taste panelists were asked to taste the fllowing 5% sucrose solutions in Heaniex watee and rate theie sweatness on a scale from 010 10, and to rate the presence af any licorice taste inthe sample on a scale from 0 to 10, Results are set forth in Table 2 TABLE 2 Congo es ‘Swewtn (O0) se Tae (10) Example 2 ‘Compound 108 Preparation by Biotrunsformation [0188], The description below sets Forth a non-tiniting hod by which the compound 10] was oblained [0159]. f-Giyeymizin (Fluka, 1g) was died in SO mL of water under gentle heating t prevent gelation. Then, 1 ‘mL of Poctinex Ultra SPL (Novozymes) was added and the ection was sired for2 days at APC. in an orbital shaker. ‘The conversion rate was 30%. Then, 20 ml. of water was added to compensate for the evaporation and the reaction ‘was stined for an additional 7 days. At that point, the Sep. 29, 2022 conversion rate wat 45%, and not much gleyrhetnie aid twas formed. The rection was Stopped by inactivating the rye t 98°C. for 10 minates, Woler was added (S00) tnd the reaction was filleed over # glass Sher dine and Iroczoiod at yok! shout 1 g (100%) of white powder Compound 108 was pried by preparative HPLC in abowt 100 consecutive injection over 4 C18 column eluted using 64% seston (0.1% formic acid), ANematvl i could aiko be prepared by lh chromography over RP-S Scape cuted with 9 gradient of Water and woctonitle {Gm 35% 10 35% ACN}.""C NMI (150 MI, Py 8168, 17.0.) 176 (0, 188 (9, 23.6 (a) 2656 ©, 268 (0), 26:9 (9,283 (@), 28.7 (@) 284 (31.6 @), 323 (329 0,373.6), 385(),395 (0, 0040), 41.70, 8.56), 801 (5), 45.6 (), 48.7 (4), 553 (0, 621 (0), 735 (, 75060, 779 (a), 782 (), 88S (d), 1073 (0), 1287 (8), 169.6), 17286), 1792 (9, 1998). Example 3 Compeninds 109/110 Preparation by Biotransformation and Chemical Synthesis 10160] The description below sets forth «non-limiting ‘method by: which the Compounds 109 and 110 were obtained, [0161]. The same protocol as for the proparation of 108 ‘was followed except the mixture of 108/110 was obtained som a fash chromatography over RP-18 silicagel eluted with «gradient of water atl acotonitile (35 wo 85% ACN). The mixture contained 80% of 109 and 20% of 110. "C NMR (150 MHz Pyr: 316.8 (g), 18.1 (). 18.6 @). 234 (), 235 (266 (0), 26.8 (0), 26.9 (), 28.7 (q), 2838 (g), 31.6 (9,322 6), 332 (), 37066), 384 (0, 393 (0, 41.7 (0,485 (9) 44.1 (6), 448 (), 45.5 (6), 48.7 (@, 558 (@), 61.9 (@, 633), 735 (@), 75 (78.2 @), 888 (4), 106.5 (2), 128.7 (@), 169.7 (9), 1726 (9, 1792), 199.4 6). 1. A muthod of enhancing a swoot taste of an ingestible composition, the method comprising introducing a favor ‘modifying compound to the ingestible composition at concentration ranging from $ ppt to 200 ppm, based on the ‘otal weight of the ingestible composition, wherein the ‘lavor-modifying compound is a compound of formula (I »US 2022/0304348 AL or a salt thereof, where RY isa hydrogen atom, — OH, or OR; R'is C, alkyl, which is optionally substituted one oF more times by substituents selected from the grup consisting of OH and Cy alkoxy: is. a hydrogen atom, — Off or —O—R™, Ca allyl, which is optionally substiuted one or more times by substituents selected from the pron eonsist- ing of —OH and C, alkoxy: or R™ is —CO}—Cg alkyd) or a lucosyt moiety RY is a hydrogen atom, a plucumnyl moiety, a Chg lucuroayl ester moiety or a glucosy! moiety fone of RY and RF is a methyl group, and the other is ~C(O)-O-R ‘A is a hydrogen atom, a glucuronyl moiety, plucuroayl ester moiety, oF alucoss moiety’ Risa hydrogen atom or C,.g alkyl and Xtis CHL, or 50, 2. The method of claim 1, wherein RY is a methyl group and R® js —C(O)-O-_R*. "3. The method of claim 2, whe som. ‘4 The method of elim 1, wherein X* is >C=0. 5, The method of any ove of claims Ito 4, wherein R* is « hydrogen atom, 6. The method of any one of claims 1 to 8, wherein R'is 1 hydrogen atm, 7. The method of any one of claims 110 8, wherein Ris ort 8. The method of any ove of elaims 1107, wherein R? is ‘hydrogen atom, 9, The method of any one of claims 1107, wherein R? is O11, 10, The method of claim 1, wherein the Aavor-modifying compound i 8 compound of formbla (13): Cs RM is a hydmgen or a salt thereof 11. (anced) 12. The method of any one oFelaims 110 11, wherein the use sto enhance the sweet laste ofan ingestible composi 13. The method of any one of claims Ito 12, wherein the ingestible composition comprises a sweetener. 14. (cancel) 15. An ingestible composition, which is a non-naturaly ‘ecurring, composition and comprises a Aavor-moditying Sep. 29, 2022 compound at a concentration ranging from $ ppm to 200 ppm, basedon the total weight ofthe ingestible composition, and wherein the lavor-modifying compound is a compound of forma (0) or a sat thereof, wherein: R'is a hydrogen atom, —OH, or OR; R'is Cyne alkyl, which is optionally substituted one oF more times by substinens selected fom the g200p ‘consisting of OH and C, alkoxy: i hydrogen stom, OH, or —O-R™ Ris C,- alkyl, which is optionally substituted one or more times by substituents selected fom the group ‘consisting of —OH and. Cy alkoxy; or Ris ‘C(O}-(C, alkyl of glucosyl moiety: RY is a hydrogen atom, a glucurony! moiety, a Cal ‘euronyl ester miiety. or gluoosy moiety ‘one of R* and Ris 8 methyl group, and the other is CO)-0--R, R* isa hydrogen atom, a glucuroay! moiety, a C.ht-

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