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WO 2015/082012 Al 11 June 2015 (11.06.2015) W P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/082012 Al 11 June 2015 (11.06.2015) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A23L 1/236 (2006.01) C07J 17/00 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/EP2013/075724 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 5 December 2013 (05.12.2013) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (71) Applicant (for all designated States except US): ANA- ZW. LYTICON DISCOVERY GMBH [DE/DE]; Her- mannswerder Haus 17, 14473 Potsdam (DE). (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (72) Inventors; and GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicants (for US only): SIEMS, Karsten [DE/DE]; UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, FeuerbachstraBe 7, 14552 Michendorf (DE). KLUGE, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Grit [DE/DE]; Muhlenberg 608, 14959 Trebbin (DE). EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, JAKUPOVIC, Sven [DE/DE]; DilgesstraBe 24, 12249 MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Berlin (DE). HETTERLING, Gregor [DE/DE]; Steglitzer TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Damm 44, 121 69 Berlin (DE). TSCHIRINTZI, Fotini KM, ML, MR, NE, SN, TD, TG). [DE/DE]; Wurtembergische Strasse 3 1, 10707 Berlin (DE). Published: (74) Agent: FABRY, Bernd; IP2 Patentanwalts GmbH, — with international search report (Art. 21(3)) SchlossstraBe 523-525, 41238 Monchengladbach (DE). (54) Title: NOVEL TRITERPENE-GLYCOSIDES AS SWEETENERS OR SWEETENER ENHANCERS Figure 1: H-NM of compound Aa - (57) Abstract: Suggested are triterpene-glycoside compounds, which are obtainable by the extraction of Momordica grosvenorii © (Siraitia grosvenori) which are useful as a sweetener or sweetener enhancer in preparations and compositions, especially oral edible o compositions. NOVEL TRITERPENE-GLYCOSIDES AS SWEETENERS OR SWEETENER ENHANCERS FIELD OF INVENTION The invention relates t o novel triterpene-glycoside compounds, which are obtainable by the extraction of Momordica grosvenorii (Siraitia grosvenori) and its physiologically acceptable salts which are useful as a sweetener or sweetener enhancer in preparations and composi¬ tions, especially oral edible compositions. STATE OF THE ART Sweetness is one of the primary taste and cravings of both animals and humans. The univer¬ sal use of naturally occurring and synthetic sweeteners to satisfy this natural craving has not been met without its accompanying physiological disadvantages, e.g. obesity, nutritional imbalance and dental decay. To overcome these unwanted disadvantages considerable re- search efforts and expenditures have been made to develop alternative compounds, e.g. as substitute for the naturally occurring sweeteners or synthetic sweeteners which have no food value and are free of caloric input. While these artificial sweeteners enjoyed a wide use, and fulfilled the requirements of a sweet taste with no food value, and could be used without providing calories or damaging teeth, they were frequently found to possess inher- ent disadvantages that prevented their use for their intended purpose, e.g. because of their toxicity (p-ethoxyphenylurea) or chromosome damage and bladder trouble (sodium cycla- mate). Thus, these sweeteners could not be safely recommended for use as a sweetener and are apparently unacceptable for consumption. Saccharin compounds are also common¬ ly used as artificial sweeteners, since cyclamates have been come under governmental re- strictions. Although saccharin compounds possess sweetness characteristics, they are unde¬ sirable as the sole sweetening agent in most food and beverage compositions because of the lingering bitter aftertaste perceived by most users. While saccharin and the cyclamates have been in common use as artificial sweetening agents for a number of years, there has been more recently discovered a series of new artificial sweeteners. For example, Horowitz and Gentili, US 3,087,821, teach the use of various dihydrochalcones having sugar substituents (dihydrochalcones glycosides) as sweetening agents. All sweet dihydrochalkones have a licorice like aftertaste and linger in the mouth for some time. Siraitia grosvenori (Luo han guo), a member of the Cucurbitaceae family, is a plant native t o some regions of southern Asia and China. The sweet taste of fruits of luo han guo mainly comes from triterpene glycosides generally known as mogrosides. There are a number of mogrosides identified in luo han guo but generally mogroside V (CAS No: 88901-36-4) has the highest concentration compared t o others (Table 1). Mogrol glycosides have the same core molecule— mogrol or oxo-mogrol and differ from each other by number and type of glycosidic residues bonded t o mogrol or oxo-mogrol molecules (US 2012/0059071, Kasai et al. Agric.Biol.Chem. (1989), 3347-3349), Matsumoto et. al. Chem. Pharm. Bu.. (1990) 2030- 2032. Several mogrosides taste very sweet, often >100x sweeter than sucrose, including the major triterpen glycoside of Siraitia grosvenori, mogroside V, and its isomer iso-mogroside V (US2011/0027413), but all of them have a certain bitter aftertaste. Major mogrosides present in Luo han guo fruits are compiled in the following Table A. Table A Mogrosid Leaves of Stevia rebaudiana are well known for its sweet taste due t o its content of sweet diterpene glycosides. One of the major sweet compounds from stevia, Rebaudioside A, is approved as natural sweetener in US (since 2008) und EU (since 2011). Apart from its sweet taste, all sweeteners from stevia have a slower onset and longer duration than that of sugar, and a bitter or licorice-like aftertaste at high concentrations (Lemus-Mondaca et al. Food Chemistry 132 (2012) 1121-1132). Another example is Symrise AG, EP 2529633 Al, which relates t o triterpenes and triterpene glycosides and/or physiologically acceptable salts thereof. The triterpenes are, preferably naturally occurring triterpenes and triterpene glycosides from Mycetia balansae, for gener ating a sweet impression in an orally consumable formulation or for reinforcing the sweet impression of an orally consumable formulation. These triterpene-glycosides differ in struc- ture from the triterpenes claimed in the present invention. Accordingly, it is a primary object of the present invention t o provide novel sweetener co m pounds and its physiologically acceptable salts, which have a positive sweet benefit in food and oral compositions. In particular, the object was t o provide sweetener compounds which are capable t o provide sweetness t o consumable compositions in a way, that the balance between the degree of sweetness and the amount which has t o be administered t o obtain a sweet effect is comparable low, t o overcome the aforesaid disadvantages associated with the prior art sweetener. It is another object of the present invention t o provide sweetener compounds without astringent or bitter-taste aftertaste. The sweetener compounds t o be specified should be toxicologica lly safe, effective already at relative ly low concentrations, wel l tolerated by the digestion, sta ble (in particu la r in norma l cosmetic and/or pha rmaceut i ca l form ulations), and easy t o form ulate and economica l t o produce. In the cou rse of extensive studies on sweeteners, the present inventors succeeded in the isolation of novel sweetener com pou nds of form ula (I) and found that these sweetener com pounds of form ula ( I) show astonishingly good and strong sweetness when com pared with that of sucrose and mogroside V. Surprisingly, it has been further observed that the sweetener com pounds of form ula ( I) have significa ntly less negative aftertaste at all and have high sweete ning power. DESCRI PTION O F THE INVENTION The su b ect of the invention relates t o a sweetener com pound of form ula ( I) (I) whe rei n R1 R2, R3 are independently of one another and denote hydrogen, hydroxyl, car- bonyl or a suga r moiety selected from the group consisti ng of a monosaccha ride and/or o li gosaccha ride. Prefera bly in the sweetener com pound of form ula ( I) the monosaccha ride and/or the mono- saccha ride units of the oligosaccha ride are selected from the grou p consisting of fructose, glucose, sucrose, xylose, maltose, mannose, rha mnose, galactose, lactose, gentiobiose, sophorose, -Glucopyra nosyl-(l-2)-[p -Gl ucopyra nosyl-(l-6)]-p -gl ucopyra nose, cel lobiose, mannitol, sorbitol, xylitol or arabitol, glucuronic acid, quinovose, arabinopyra nose, arabino- fura nose, xylopyra nose, xylofu ranose and/or apiose (2,3,4-tri hydroxy-3-(hyd roxy- methyl)buta nal), and whe rei n the oligosaccha ride consists of 2 t o 5 monosaccha ride units. The term "monosaccha ride" mea ns the sim plest form of suga r. Monosaccha rides are the most basic units of biologica lly importa nt ca rbohydrates. Exa mples of monosaccha rides in clude glucose (dextrose), fructose (levulose), galactose, xylose and ribose.
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