JPS63112964A - High titer sweetener - Google Patents

Abstract

(57) [Abstract] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention is applicable to sweet food products. The present invention relates to novel flavoring agents for drinks, sugar confections, chewing gum, hygiene products, cosmetics, pharmaceutical and veterinary preparations and the like. It also relates to products and compositions containing such sweeteners. [Prior art] A chemical compound that exhibits sweetness properties, ``suosa
n) J and its derivatives have been extensively studied since their discovery by Betersen and Müller in 1948 and constitute a chemical series. (For example, “Human chemosensory organs (
"Relationship between structure and activity in chemical reception", "Beets", Ri. D336
-337. Applied Science Publications, London, 1978: Crosby and Wingard p. ieo. 1. Advances in Sweeteners, Applied Science Publications, London, 1979; Tinti, Norre and Pel.
/laVi no shidabensm. unders. Fo
rsch. , 175, 26flr268. (1982). These compounds have not been used commercially as lunar agents. The reason is (1) he
The substances that it consists of emit highly toxic molecules. (e.g. f: suosanJ yields P-nitroaniline). (2) Some of their constituents contain the frayed or first clade, which undergoes gradual hydrolysis in aqueous solution. (3) Other constituents have an undesirable bitter or licorice-like taste apart from the sweet taste. Generates an aftertaste.In connection with the present invention, Zarani Yuki and rnoue
(Journal of the Chemical Society of Japan Nα11, 2140-43 (19
74) Chemical Rua 7,1-Lact Vo1.82
No. 140061p (1975) discloses N-((4
-chlorophenylamino)iminomedyl)-S-alanine (Chemical Substance Index Vol. 7)
5-85. 1972-1976, p. 1067CS
) is described. This compound does not exhibit strong sweetener properties like the compounds of the present invention. Also related to the present invention are the inventor's disclosures, European patent application no.
Released on September 24, 1986, Corresponding French National
There is an application Nα85.04241. These applications are related to aspartame (aspartame).
) (L-aspartyl-L-phenylalanine methyl ester) (L-aspartyl-L-phenylalanine methyl ester).
a n derivatives are disclosed. That sweet SU
osan/dipeptide derivatives are also characterized by the substitution of oxygen in the urea structure by sulfur to form a diourochord and by nitrogen to form a guanidine structure by carbon to form an amidine structure. It is said that Such a compound is described as having a sweetness potency of 55.000 degrees of the sweetness of a 2% sucrose solution on a per day basis. On the other hand, limitations regarding solubility and/or instability are disadvantageous in the presence of high temperatures. MAIN SUMMARY OF THE INVENTION According to the present invention, substituted guanidino and ethanamidino sweeteners are represented by the following general formula. Here, 13. I4 and Xs are one selected from the group consisting of the following groups, and are the same or different. If, Br, CF3, CF2 CF3,
C11z CF3. Alkyl of CI -C4, CIl -NOCI+ 3
, CI-NOH. CHO, C1120C113, ClI20H, Cj,
CM, C0CF3. COCl - Alkyl of C3, CONH2. C0NHC+ -C3 alkyl, CON (CI
-C3 alkyl) 2. CQOCI-C2 Al4-R, C00I13, F, I, Nl+2
, NHC+ -C3 alkyl. N (CI-C3 alkyl) z , NHCll
0, NlIC0Ct13. NHCONllz, NH3O2CH3, NO2, O
C+ -C3 alkyl, 0COCtl 3 , 01
1. SC+' C3 alkyl. 30 CI -Cs alkyl, 5o2C, -C3 alkyl, SO2NH2, 5o□NlI C, -C
3 alkyl. 302 N (alkyl of CI-h)2. and 30
3 II: where A is one selected from the group consisting of N and C, where R+ is a hydrogen atom, or R1 is a saturated, unsaturated, acyclic, G1 formula from C1 to C4 or a group of mixed hydrocarbons or modified hydrocarbons, where the modified hydrocarbon group has 1 to 2 carbon atoms of N, O, S, Cl,
can be substituted by one to two of the same or different heteroatoms or different heteroatoms selected from the group consisting of Br, I, and can be substituted by one to three, where R2 is saturated, unsaturated, from C2 to Cl3; saturated, acyclic,
A cyclic, mixed or modified hydrocarbon group, where a modified hydrocarbon group is defined as a cyclic, mixed or modified hydrocarbon group in which from 1 to 4 carbon atoms are N
, 0. One or four of the same or different heteroatoms selected from the group consisting of S, CL Br, I can be substituted, and 1 to 5 hydrogen atoms can be replaced by 1 to 5 fluorine atoms. Here, R1 and R2 can be condensed, where R3 is one selected from uJ consisting of alkyl of 11 and CI -C3, and here R4 is one selected from the group consisting of ■ and CH3. However, X: J, xs, R3 and U R4
When I4 is CN or NO2, R1 and R2 are O
Not N or 0C113, I4 is H, CF3, CHO, CI, CN, CO
When Cl13, F or NO2, R+
is not NOz, 5OCH3 or 5OC2Hs,
R2 is NO2, SOR, 5o2ft, 502NHI
Rather than t or SO2N(R)2, R is an alkyl, cycloalkyl, or allyl group of up to 10 carbon atoms which can be substituted by one or two atoms of sulfur or oxygen. modified hydrocarbon q
What is intended by the term R2 is a modified hydrocarbon group of 02, where one atom of carbon can be substituted by one atom of nitrogen, so that part of the hydrocarbon of C2 is replaced by cyan of CN. can. Further, as an example, where R2 is a modified hydrocarbon group of 03, one carbon atom is replaced by a nitrogen atom, and two carbon atoms are replaced by two oxygen atoms, so a part of the hydrocarbon of 03 is -NO2 can be replaced by nitro. N, 0. S, CI, Sr. Other substitutions of hydrocarbon carbons by I'1ii- or different heteroatoms selected from the group consisting of (1) are likewise contemplated by the present invention. The restriction that R2 is a C2 to C,3 group was established as a result of limiting solubility. Although it is possible to make R2 longer than the 13 carbon limit mentioned above, it is expected that the C2 chain itself; be done. Preferably the sweetener is 8 is N and R4 is 11;
R3 is selected from the group 11 and C) 13, and R1
is selected from the group consisting of 11 and CI13. Sweeteners x3 and x5 are also tl, Sr, CF3, Cl
l3, C13, ``sweeteners are also preferred from the group consisting of ×4 H, CN, C00CHz
, F, and NO□. It is also preferred that the sweetener is selected from the group consisting of R2. Straight chain alk (en) (Yn) C2-Cp of Ml
s. Branched chain alk (en) C3 of Ml, -cr3°C
yclo alk (en) yl R3-C13, A
lk (en) yl cycloalk (en)
yl's C4-CH3゜Cyclo alk (en)
C4-co of yl alk (en) yl. Alk (all) yl cycloalk (en)
) yl alk (en) yl's cs -CH3゜Alk (en) yl bicyclo alk (
en) C7-C of yl. f! Cy of life bicyclo alk (en) yl
-Ca3. 8 Ik (en) yl condensation bicyclo alk
(en) Cs-co of yl. condensation bicycloalk (en) yl alk
(en) Cs-c mouth of yl. alkenyl condensation (7) bicycIoalk (O
n) C9-CD of ylalk (en) yl. C of condensation trtcyc+o alk (en) yl
,,-C,. Alk (en) yl condensation tricyclo
CIl -C1l of alk(en)yl. condensation tricyclo alk (en) yl a
lk(en)yl Co-Ca and Alk
(en) yl, condensed tricyclo alk
(en) yl alk (en) CH3° of yl These sweeteners in which R2 is particularly preferred are one selected from the group consisting of the following groups. n-C%'++, n-CgH+s, n-Cl
yH+5. Cl1(CHt3)(C1lz)2CH3. Cl1(Cth)(C112) 3 CH13゜(C
112) 3C1l (CH3) 2 . (CH2) 4 C8(CH3) 2 . (Ct(z) s Cal (Cfh) 21
(,H,,Cs-cycloalkyl of CIO, CH2
C6H5. C112-c-C6H・, CI ((:13)
C(+5. C1l (CH3) -c-C,H,,, (CH12
) 2 ctHf. (CH2) 2 -c-c, 811 , CH(CH3
) 'ClI2c, Hs. C1l (CHt31 C11z −+C(H1+
, C(H4(CHt3) -c6CIocycloalkyl(CH3).CHt2((H,+(CHt3), CH2-
c-CgH+o (C113). Cll (Ch) C(H4(CH3). (:ll ((:113) -C-C,Hro (
CHt3). (CHt2) 2 C11(c-C3H5) 2゜(
CHt2)3CH(C-C5Hs)2. Cll(CH3)(CHt)2C11(c-Cs
Hs) 2. Cll(C113)(CHt2)2Cl1(I
e-CB+5) 2. Naphthyl, 5.6.7.8-tetrahydronaphthyl, perhydronaphthyl, indenyl, indanyl. naphthyl (CHt3), 5.6.7.8-tetrahydronaphdi)Ll (C113), bar t:
Toos7chi/L/ (C113), -1'ndenyl (CHt3), intanyl (CH3), 7
End/L/, Cl12 f edge) Ii, C11
2-5,6,7,8-tetrahydronaphthyl, CH2
-Perhydronaphthyl. CH2-intenyl, Cl12-intenyl, C
112-naphthyl (CHt). CH2-5,6,7,8-tetrahydronaphthyl (CH
3). CH2-perhydronaphthyl (CH3). C112-indenyl (C)h). C)+2-indanyl (C)lz), adamantyl. CHtZ-adamantyl, CIl(CHt3)adamantyl. CH2-adamantyl (CH3), gokoi' e-
Preferred sweeteners also include those listed above, where R2 is a modified hydrocarbon group, where up to 4 carbon atoms are C or S for substitution of 0112, CI1, N to replace Ni+, CH
0 for substitution of 2 and Cj, c for substitution of CH3
s. Br, I can be replaced by the same or different heteroatoms selected from the group consisting of these heteroatoms. There, up to five hydrogen atoms can be replaced by fluorine atoms. Further, R2 is N(CHt3)CrHs. Pyridinyl, piperidyl, homopiperidyl, indolyl, indolinyl, isoindolinyl, quinolyl, isoquinolyl, pyrazinyl, pyrimidyl. Intazolyl, quinoxalinyl, quinonazolinyl, vinylinyl, 0CH2Qk'9- #pyranyl, benzofuranyl, methoxyphenyl, methyloxycarbonylphenyl, 3,4-methylenedioxyphenyl, morpholinyl, benzoxazolyl, ethanamidophenyl,
Nitrile, nitro, thiophenyl. Benzothiophenyl, 2.2.4.4-tetramethylthiacyclobut-3-■+, Thiozolyl, Isothiazol IJ, 5o2c, )l, , SOzCg
) In, 5O2CrrH+s. A sweetening agent selected from the group consisting of chlorophenyl, fluorophenyl, trifluoromethylphenyl is preferred. Other preferred compounds are those represented by the following general formula. Here, R1 is ■ or R1 is CI (3. Especially ×
3 and XS are 11, said X4 is CN, and X3 and Xs are CF, , CIl, , CI, F
One selected from the group consisting of, where x4 is H and CN
Preferably, the compound is one selected from the group consisting of: Particularly other preferred compounds are CH(CH3)Cj)(r, CH2C6H6,
CI (CH3)-C-Cc Hl, +1 l
'-C6H11,,c-CFH+>:,c
-CgFLs *'C-CIIH+7,;
C-C-1eHI111* SChCgH5*302
C7) (1) The most preferred compound is R1 is ■ and C113, where R3 and R4 are ■: ×3 and XS are ■, ×4 is CN, or ×3
and Xs is one selected from the group consisting of CF, , CH, , CI, F, X4 is one selected from the group consisting of II, CM; and where 82 is C1l (
CH2) QHr, CH2C6H La
. CI (CH3) -(-QHn, , +c-C4
)111, ,e-07)1+3. C-CzeR1shi, e-eqHiIF, ,
c-C1aH+qHlSO2CA Fl2, 5O
It is a compound selected from the group consisting of 2C7H+3. Particularly preferred compounds are N-

[Tocyclononylamino(4-cyanophenylimino)methyl]-2
-Aminoethane 1m (Rt and x3 and Xs!; t H
r$5su, X4 Get CM Te(T) '), R2
HaC-Cq'rA+ITt) Nido[tocyclooctylamino(4-cyanophenylimino)medyl]-2-aminoethane M(Rt and x3 and Xs HaHte, X+HaCNte, R2Gtc-cthL5
): N-[N-(S)-α-methylpentylamino(3,5
-dichlorophenylimino)methyl]-2-aminoethanoic acid (Rt)
Ite is present, R2 is (S)CIl(CIl3) CgF
(5) Nido[N-cyclooctylamino(3-chloro-4-cyanophenylimino)methyl 1-2-aminoethanoic acid (Rt
There is Nr, x4 is CN, and R2 is c-C6Ih5
) diN-[N-cyclooctylamino(4-cyano-3-methylphenylimino)methyl]-2-aminoethanoic acid (Rt
31' (T) Ri, X4 G;i; CN Teari, R2
G; t, C-C5HL5); N-[8-pendelamino(3,5-dichlorophenylimino)methyl]-2-7 minoethanoic acid (Rt and x4 are 11 Te,
Xs ト
to[phenylsulfonylimino(4-cyanophenylamino)methyl]-2-aminoethane M (Rt. X3, Xs Lt H1'2F+'l, XiG;
tcNr, R2 is SO2C6H5); N-(8-(S)-1-cyclohexylethylamino(
3,5-dichlorophenylimino)methyl]-2-aminoetha>'m (Rt tX4 G, t Hr present, X
s HaCj Teaari, R2 is (S)C1l(CH3)
-1'-CI6Hu);N-[N-(S)
-α-methylpentylamino(4-cyanophenylimino)methyl]-2-aminoethanoic acid (Rt, X3
ToXs HaHtei'), L HaCNT: AV), R
2 is (S)CIl(CIl3)C6ex):
N-[N-cyclohebutylamino(3,5-dichlorophenylimino)medyl]-2-amino acid (Rt and x4
is +1 te@su, x3 and Xs have c1 te, R2 is C-
It is CI1Hta. The preferred sweetener of the invention is J3Jl salt, sodium. Contains agents selected from the group of physiologically inhibited salts consisting of potassium, ammonium, calcium and magnesium salts. Flavored food products, beverages, confectionery, chewing gum, pharmaceuticals, veterinary preparations according to the invention. Methods for flavoring toilet, cosmetic and hygiene products and preparations are provided. Furthermore, the present invention provides a sweetener composition characterized in that it consists of a highly intense sweetener effective h1 and a physiologically acceptable carrier as a filler. Preferred carriers are polydextrose, starch, maltotegistrin. Cellulose, methylcellulose, carbomethylcellulose, hydromethylcellulose, microcrystalline cellulose, sodium alginate. Pectins, gums, lactose, maltose. glucose, leucine, glycerol, mannitol,
Sorbitol, sodium monocarbonate, phosphoric acid. selected from the group consisting of citric acid, tartaric acid, fumaric acid, benzoic acid, sorbic acid, propionic acid and its sodium, potassium, calcium salts and mixtures of all of the foregoing. According to the invention, the composition comprises (1) a sweetener according to the invention;
2) It is characterized by being composed of different sweeteners. Different sweeteners are sugar or highly potent sweeteners and sucrose, corn syrup, fructose,
Aspartame, alitame, neohesberidine dihydrochalcone, hydrogenated isomaltose. stevioside, L-sugars, glycyrrhidine, xylitol, acesulfame-K,
Saccharin (sodium, potassium or calcium
p), cyclamine fil (cyclamic a
cid) (sodium, potassium or calcium salts), trichlorogalactosucrose, monellin (m
onellin), thaumatin and mixtures thereof. The present invention appears to relate to improved derivatives of '5uosan', which in particular contain a guanidino group (
guanidino), guanidium group (guan
idinium) or ethanamidino (ethana
It is characterized by the substitution of urenoids or thioureido by midino) groups. The present invention shows that these new compounds not only preserve sweetness, but also preserve the sweetness of urenoids or thiourides, as they are up to 200,000 times more potent than sucrose in 2% sucrose solutions. shows an unexpected improvement in increasing the potency of sweeteners in terms of sweetness. The present invention utilizes glycyrrhizin and thaumati.
Similar to n, 5uosan makes possible the improvement of eliminating the bitter or licorice aftertaste possessed and characteristic of the corresponding urenoids or thioureido derivatives. Zarani T [flavoring agents have the disadvantage of having a dull metallic aftertaste of saccharin or aceyulfame-K. In fact, according to the present invention, the sweeteners of the V7F standard have d3 sensitive organ properties and are virtually indistinguishable from sucrose. The present invention also relates to a method for flavoring products (and for sweetened products) by adding an effective amount of a flavoring agent according to the invention. "Effective amount" means an amount that can be detected as sweetness by human physiological senses. The present invention relates to a composition containing a sweetening agent in cooperation with a compatible carrier or other sweetening agent. Mixtures of sweeteners of the present invention may also be used in practicing the present invention. DETAILED DESCRIPTION OF THE INVENTION The high potency sweeteners of the present invention are prepared by use of a number of synthetic techniques that have been disclosed in the literature. These techniques are summarized in a recent report by Maryanoff (C, Haryanoff, R,
C, 5tanzione. J.N., P.Iampin, and J.E., Hills.
, J, Org, Chem, 19th competition, 51.1882
-1884). The technique is roughly described in the following paper. J. Hed, Chem., 1978. No. 21
．． pp, 773-781: ChChem,
Be hotpot 100. pI), 591-604; J, f
ur Prakt, Ct+eIll, 1977, N
(1319,l)D, 149-157: The Ch
emistryof Am1dines and lm
1dates, S, Patai, cd,
MileV-TntOrSCienCe 1975
, I)l), 283-348. The first involves the production of an isothiourea intermediate and the second involves the transformation of a carbodiimide intermediate. According to the isothiourea method, intermediate carriers of groups or easily released and activated atoms use the letter L in subsequent reactants. The easily released and activated atomic group is preferably selected from compounds consisting of S-alkyl, 0-alkyl, 0302-furyl, SO3H, and halogen elements. As a general principle, the reaction takes place between intermediate reactants and appropriate interdependent amines, and the subsequent compounds come into contact with each other and react. X / upper 'D type te Xs, X4, X5, 8+
R2+R3+R4 is the same as the one already made by Sadatsuru,
L indicates an activated base. These reactions are carried out using water or the organic solvent ethanol. The reaction can be carried out in methanol, acetone, chloroform, carbon tetrachloride or pyridine at temperatures ranging from room temperature to the boiling point. The selection of solvent and temperature used is [
and the reactivity of the amine used. In reactions comprising reaction 2.3.4.5.6 above, it is preferred to first protect the carboxyl group of the alpha amino acid in the form of an ester, such as a methyl, ethyl, tert-butyl or benzyl-ester. . In this case, in order to obtain the compounds according to the invention, it is necessary to remove the Hosudake by the most suitable means, either by saponification with a sodium hydroxide solution or alternatively by hydrolysis with a hydrochloride solution. can be done. Several methods can be used to prepare the intermediate. Corresponding thiourea derivatives are generally prepared as follows. One of the preferred methods of synthesis used to obtain these thiourea derivatives is the reaction of an alkyl or allyl isothiocyanate with a suitable amine. The reaction is carried out at temperatures ranging from room temperature to the boiling point and, depending on the interreactivity of the two compounds, is carried out in an organic solvent such as ethanol, methanol, chloroform or acetone. The following reactions can be carried out in this way: A preferred process consists of converting the S-alkyl derivative into the thiourea derivative obtained in this way. A preferred activating group is 5=CI13u, for example R3 is H in the following compounds. These intermediates can be prepared by heating the corresponding thiourea derivatives with an alkylating agent such as methyl iodide or dimethyl sulfate in a melt bath such as acetone or 2-butanone at air temperature, depending on the reactivity of the material. It can be obtained by processing at temperatures ranging from to boiling point. Methylisothiourea J Q
The body is thus obtained in the form of iodide or sulphate salts. These salts are then treated in a solution of sodium hydroxide or hydroxide to give their base form MM. They then use the presence of a tertiary amine such as sodium hydroxide, potassium hydroxide or triethylamine in a mixture of alpha amino acids, ethanol and water, from air temperature to boiling point, depending on the reactivity of the substance. Condensation occurs over a temperature range. 1 → (Me) Summon NR3C0J & Toshu CH (Garden) CO
OiAccording to this general method, alkyl or allyl isodiocyanate (X3Y4Xs) PhNC5Lt
lINR+ React with the amine of R2 and '11fA in an organic solvent (X1XqX5) PhNC5NR
+ R2(7) yields urinary The temperature is varied from steady to 100°C depending on the reactivity of the thiourea, thus forming a crystalline isothiouronium salt [(X3奥X5) F'1I
N=C(N
I R2) 5C113 is obtained by methylene chloride extraction and recrystallization. This thioisourea is 1+ there
2 NCII (R4) React with C00II amino acid (foam XJ'::5) PhN=C(NRI
I'? 2) Obtain guanidine of NIIC)l(L)C00II. This reaction can be carried out in water or an organic solvent, at a temperature of tlz NCII (R4)C
The temperature is varied from air temperature to 100° C. depending on the properties of the OOH amino acid. The guanidine is then purified by recrystallization or quasi-methods. Pen'I'El exchange';
/7 Herring (X1XqX5), PhNRa C (NRI
R2)=NCH(R4) COO can be obtained in a commercial solvent by reaction of a tetra-substituted guanidine with an alkylating agent. A second general method is based on the use of carbodiimide intermediates. The carbodiimide intermediate can be obtained by the action of phosgene or by a mixture of peroxymolecules of triphenylphosphine, a tertiary amine and carbon tetrachloride in an organic solvent of dichloromethane or carbon tetrachloride in the temperature range from room temperature to the boiling temperature. It will be done. Second method 2 carbodiimy × 1-2 (× μ, [,)
PhNC3 R2NH2 (x3x4x5) Ph-NlIC5NII-Rz
Phz P-CC 4th → (〆3×UX5) Ph-N'C=N-R
zEh N/CH2C1z (carbodiimide) N2 MCII (C114) COOff (X3X4X
5) PhNII-C(-Nllz)NIICH
(Rs)COOII-(MeiX+X5)I'hNl
'b-C(NF2+l'!J=%Cf1(F!+)Co
oH According to this general method, (X1X4X5) Ph-NC8 of allyl isothiocyanate is R of the primary amine.
Condensation with 28H2 gives N'-disubstituted thiourea (,)
6X+%) to generate the ph-set IC3-NHR2. After purification by standard techniques such as recrystallization or chromatography, the thiourea is reacted with refluxing dichloromethane with one portion each of triphenylphosphine, carbon tetrachloride, and triethylamine to form carbodiimide (X
)X4X5) Convert to Ph-NCN-82. The carbodiimide is not separated, and the carbodiimide solution is directly converted into H2NCH(R4)C(1ON,!: Reaction N i!
Tet'J v1 exchange Kuanishi 7 (X3X4X'5)
PhNH-C(-NF12)NIICH(Ra)C
Obtain OO11. Tetra- and penta-substituted guanidines can further be obtained by alkylation of tri8m guanidines with alkyl halides. The sweeteners of the invention can exist as an equilibrium mixture of tautomeric forms. The sweetener is represented in the general formula as a tautomeric form with C=ARI 82 unsaturation. however,
This tautomeric form is R3=H and C=NCH(R4)00
011 Temult8ni (XvX'v,)G) PhN-
In equilibrium with respect to the tautomers of C, it becomes highly proformal. According to the invention, RI+ R2+ R3+A
Depending on the nature of the sweetener, the sweetener can be present in zwitterion or acid form. They can thus be converted into their salts by acids or by physiologically acceptable organic or inorganic bases. One of the best ways to prepare such salts is to concentrate a mixture of a compound according to the invention in aqueous solution with the appropriate acid or with an organic or inorganic base by drying in vacuo. Preferred salts according to the invention are basic acids or sodium, potassium, ammonium, calcium or magnesium salts. The 11 flavors of the present invention can take the form of balanced mixtures of tautomeric forms. Thus, the next tautomeric form is A
is obtained when is equal to N and R1 and R3 are equal to 11. If eight equals N, R1 equals C113 and R3 equals H: or if A equals H, R1 equals 11 and R3 equals CH3; A equals C and R equals 11 Sometimes the following formula applies, for example: This is why the sweeteners according to the invention are represented in the general formula by resonance hybrids or by one of the tautomeric forms in the descriptive part of the invention. The tautomeric form is similar to the pH: X3+XJ+XS+R+
, represents the knowledge that depending on the nature of L and R3, other tautomeric forms must necessarily be balanced. The sweeteners of the present invention are added to foodstuffs in which it is desired to have a sweet taste. The present sweeteners are added to such products in an effective manner to provide the desired level of sweetness. Optimal sweetener 8'! For example, the sweetness potency of special sweeteners, product storage and use conditions, I! Special Ingredients of J Products 9 It is highly dependent on a number of factors such as the flavor profile of the food product and the desired sweetness level. Those skilled in the art can readily determine the optimum R to be used in a particular formulation of the food product by routine experimentation. Typically, the present sweeteners are added to the foodstuff by weight from about 0.0005% to about 0.2%, advantageously from about 0.0005% to about 0.15%, by weight.
Preferably from about 0.001% to about 0.1% by weight is added. Of course, mfflt will be included in the high percentage of sweeteners (S). Suitable products sweetened with the sweeteners of the present invention are those comprising foodstuffs (human or animal ingestible products) where a sweet flavor component is desired. ), beverages (alcoholic, soft drinks, juices, carbonated drinks), sugar confectionery products (candies, chewing gum, baked goods, baked goods, breads, etc.), hygiene products, cosmetics, pharmaceutical preparations and veterinary products. The sweeteners of the present invention can be added in pure form to food products imparting a sweet flavor.However, due to the high H potency of the sweeteners of the present invention, they may be mixed with carriers or fillers. Suitable carriers or fillers include polydextrose, starch, maltodextrin, cellulose, methylcellulose, carboxymethylcellulose, hydroxymethylcellulose, microcrystalline cellulose, cellulose derivatives, sodium alginate,
Vectin gums, lactose, maltose. glucose, leucine, glycerol, mannitol,
Sorbitol, sodium bicarbonate and phosphoric acid. Citric acid, tartaric acid, fumaric acid, benzoic acid, anti-sorbic acid,
Propionic acids and their sodium salts. Potassium salts, calcium salts and mixtures of all of the above. The sweeteners of the present invention can also be used as the sole sweetener in food products. It can also be used in sweet food products as a mixture of one or more of the sweeteners of the invention. Additionally, the present sweeteners can be used in combination with other sweeteners such as sugars (sucrose and fructose). Plus, corn syrup. Dipeptide sweetener (aspartam)
e) and alitame ) and gl
ycyrrhizin, xylitol, sorbitol,
Mannitol. acesulfam-k,
thaumatin, monellin,
cylamates, saccharin. nd'hesperidin dihydrocha
lcone, hydrogenated isomaltrose, 5tcvi
It can be mixed with other sweeteners such as L-sugar, trichlorogalactosucrose, and mixtures thereof. The sweetness potency of the compound prepared in the following example is 6.
It is evaluated by one panel of two connected appraisal cups. The compound is compared with the first one in taste in aqueous solutions of scaled concentrations, and the object to be compared is with a prepared solution of sucrose, the concentration of which is 2% or 2%, 5% of the concentration corresponding to that commonly used. % and 10%. The sweetening potency of synthetic sweeteners varies depending on the concentration of the sucrose solution used as a reference. The sweetening potency of a compound tested with respect to sucrose thus corresponds to the Ifi) ratio at which there is equal sweetness intensity between the compound and sucrose. The sweetness between the compound solution being tested and the sucrose prepared solution corresponds to the weight a ratio at which the sweetness is considered by multiple connoisseurs to have the same sweetness intensity. The present invention is a compound having substituents on the phenyl group at the 3 and 5 positions of meta'11'lA. The presence of special substituents at these positions aids in the sweetness potency and thermal stability of the compound. C1 at the 3 and 5 positions of the meta-substitution of the benzene group
It is known that derivatives in which 13 or C2 are di-substituted are about 40 times sweeter on a weight basis than the same Fυ derivatives substituted only in the 4 position of the para substitution. Ortho-substitution of the phenyl group results in compounds that are not at all sweet or slightly sweet. The method and advantages of carrying out the invention will be readily understood from the following description of non-limiting examples. The compounds of the invention described in the following Examples and Tables are purified by standard methods such as recrystallization or chromatography. Its structure and 11! The accuracy was verified by conventional techniques such as thin layer chromatography, high performance liquid chromatography, IR absorption spectroscopy, nuclear magnetic resonance and centiful analysis. [Example] JJL-N-[N-(S)-α-methylbenzylamino(phenylimino)methyl 1-2-aminoethane! ! I: This compound contains glycine and N according to the experimental method described in Example 2.
-(S)-α-methylbenzyl)-N'-phenyl-8
-obtained from methylisothiourea. (Yield: 53%, melting point 209°C) The sweetening capacity of this compound is equivalent to 5000 times the sweetness of a 2% sucrose solution based on ff1ffi. Wenjinggol2=N-[N-(S)-α-methylbenzylamino(3-
Bromophenylimino)methyl]-2-aminoethane F
li:r 1st step: Method for producing N-(S)-α-methylbenzyl-N′-(3-bromophenyl)thiourea. 5 g (41111 mol) of (S)-α-methylbenzylamine and 89 (37 fnmol) of 3-bromophenyl isothiocyanate were mixed with 50 cm of 95% ethanol and stirred at 20°C for 4 hours. Vacuum and concentrate for drying. Hexane 200cd
After washing with
7%) with a melting point of 103°C. Second step Nido(S)-α-methybenzyl-N'-(3-bromophenyl)-8-methylisothiourea: 11,59 (3
4 mmol) of the obtained compound and 7 of methyl iodide.
．． A mixture of 24 g (51 mmol) was heated for 10 hours at 20
Stir in 100 cm 1 of 2-butanone at °C. After concentrating the mixture for drying in a vacuum, the residue was 200
Cd in ethyl ether and separated by 1 filtration. 15.1 g (92% yield) of S-methylisothiourea derivative is obtained in the form of hydroiodide salt. This salt is next 1N of sodium hydroxide? Dissolved in 200d of i liquid. The alkaline mixture obtained is extracted three times at 100 d with dichloromethane. After drying over anhydrous sodium sulfate, 9.5 g (yield 586%) of S-methylisothiourea derivative was obtained in the form of a colorless oil. 3rd step Production of aminoethanoic acid of nido(S)-α-methylbenzylamino(3-bromophenylimino)methyl]-2-: 39 (40.8 mmol) of glycine and 1.6 g
(40,8 mmol) of sodium hydroxide was mixed in 5 d of water, and 9.5 g (27,2 mmol >t(S)-α-methylbenzyl-N'-(3-bromophenyl)-8 - add 100 CI 11 of methylisothiourea to a 95% ethanol solution.
Heat at ℃. After cooling, the solution is concentrated to dryness. The residue is dissolved in 60 cm of water and the resulting solution is washed with dichloromethane (3 x 50 d) and then acidified to I)H by adding 1 lcf of 6N solution to 7. The desired guanidino derivative precipitates and is separated by filtration. 6.4g (
A compound with a yield of 162% was obtained (melting point: 212°C). The sweetening ability of this compound is 'I^i! It is equivalent to about 25,000 times the sweetness of a 2% sucrose solution. Marumi ■ Synthesis of UniN-[N-(S)-α-methylbenzylamino(3-trifluoromethylphenylimino)methyl 1-2-amineethanoic acid: C'3 This compound was described in Example 2. N-(S
)-α-methylbenzyl-N'-(3-trifluoromethylphenyl)-8-methylisothiourea and glycine (yield: 34%, melting point: 158°C). The sweetening capacity of this compound corresponds to approximately 7.500 times the sweetness of a 2% sucrose solution on a weight basis. Jogotan A: Synthesis of N-[N-(S)-α-methylbenzylamino(3-methylphenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2. −(
S)-α-Methylbenzyl-N'-(3-methylphenyl Is-Methylisothiourea obtained from glycine. (128% yield, melting point 205°C) The sweetening potential of this compound is based on weight. It corresponds to about 12,000 times the sweetness of a 2% sucrose solution. Fumikuu Goji: Synthesis of N-[N-(S)-α-methylbenzylamino(3-ethylphenylimino)methyl]-2-aminoethanoic acid: This compound was prepared using the experimental method described in Example 2.
)-α-methylbenzyl-N'-(3-ethylphenyl)-8-methylisothiourea and glycine. (Yield 42%, melting point 205°C) The sweetening capacity of this compound corresponds to approximately 4500 times the sweetness of a 2% sucrose solution on a weight basis. Synthesis of N-[N-(S)-α-methylbenzylamino(3-chlorophenylimino)methyl]-2-aminoethanoic acid: This compound was prepared according to the experimental method described in Example 2. N-(
S)-MebolbenzyruN'-(3-chlorophenyl)-3-methylisothiourea and glycine. (Yield 22%, melting point 178°C) The sweetening potency of this compound is approximately 30,000 times as sweet as a 2% sucrose solution on a weight n) basis. Synthesis of N-[N-(S)-α-methylbenzylamino(3-cyanophenylimino)methyl]-2-aminoethanoic acid. -(S
)-α-methylbenzyl-N'-(3-cyanophenyl)-S-methylisothiourea and glycine. (63% convergence, melting point 190°C) The sweetening potency of this compound corresponds to approximately 5500 times the sweetness of a 2% sucrose solution on a weight basis. Godan Maruoka: Synthesis of N-[N-(S)-α-methylbenzylamino(3-dithophenylimino)methyl]-2-aminoethanoic acid: This compound was prepared according to the experimental method described in Example 2. G (S)
-Methylbenzyl-N'-(3-nitrophenyl)-8
-obtained from methylisothiourea and glycine (Yield 13
9%, melting point 195°C). What is the sweetening power of this compound? 1! This corresponds to about 6000 times the sweetness of a 2% sucrose solution based on the sweetness. Synthesis of N-[8-(S)-α-methylbenzylamino(3-methoxyphenylimino)methyl]-2-aminoethanoic acid: Cll3υ This compound was prepared according to the experimental method described in Example 2. N-(
Obtained from S)-methylbenzyl-N'-(3-methoxyphenyl)-8-methylisothiourea and glycine (yield 178%, melting point 191°C), the sweetening ability of this compound is based on It is approximately 4500 times sweeter than a 2% sucrose solution. Synthesis of N-[N-(S)-α-methylbenzylamino(3-methylcaptophenylimino)methyl]-2-aminoethanoic acid: lhS This compound was prepared according to the experimental method described in Example 2. N-(
S)-α-Methylbenzyl-N'-(3-methylmercaptophenyl)-3-methylisothiourea and glycine (yield 59%, melting point 186°C). The sweetening potency of these compounds corresponds to approximately 5500 times the sweetness of a 2% sucrose solution on a weight basis. Synthesis of N-[N-(S)-α-methylbenzylamino(4-trifluoromethylphenylimino)methyl 1-2-7 minoethanoic acid: This compound is described in Example 2 According to the experimental method
)-α-methylbenzyl-N'-(4-trifluoromethylphenyl)-3-methylisothiourea and glycine (yield 9%, melting point 168°C). The sweetening potential of these compounds is
The sweetness corresponds to approximately 500 times the sweetness of a 2% sucrose solution.・ Back bottom ■ Uni: Synthesis of N-[8-(S)-α-methylbenzylamino(4-methylphenylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2. (S)
)-α-methylbenzyl-N'-(4-methylphenyl)-8-methylisothiourea and glycine (
yield: 126%, melting point: 137°C). What are the sweetening powers of these compounds? Based on 12ffi, it corresponds to approximately 800 times the sweetness of a 2% sucrose solution. Synthesis of 1-5-unit N-[N-(S)-α-methylbenzylamino(4-chlorophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized as N-(
S)-α-Memethybenzyl-N'-(4-chlorophenyl)-3-methylisothiourea and glycine (yield 42%, melting point 146°C). The sweetening capacity of these compounds is 2% based on Kawa R.
It corresponds to about 3,000 times the sweetness of sucrose solution. Synthesis of N-[N-(S)-0-methylbenzylamino(4-cyanophenylimino)methyl]-2-aminoethanoic acid: This compound was prepared according to the experimental method described in Example 2. (S)
)-α-methylbenzyl-N'-(4-cyanophenyl)-8-methylisothiourea and glycine (yield 35%: (α)o”+112°5° (C-1
, 0, May H(J); melting point 206°C). The sweetening capacity of this compound is approximately 28,000 times the sweetness of sucrose for a 2% sucrose solution on a weight 8 basis.
20,000 times for the 5% sucrose solution and approximately 10,000 times for the 10% sucrose solution. Synthesis of N-[N-(S)-α-methylbenzylamino(4-acetylphenylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by the experimental method of Example 2. S)-α-
Memethybenzyl-N'-(4-acetylphenyl)-8
-obtained from methylisothiourea and glycine (yield 24%, melting point 173°C). The sweetening capacity of this compound is approximately 800 times the 11 taste by weight of a 2% sucrose solution. Synthesis of N-[N-(S)-α-methylbenzylamino(4-meth4-dicarbonylphenylimino)methyl]-2-adannoethanoic acid: This compound was synthesized according to Example 2. N-(S)-α- by experimental method
Obtained from methylbenzyl-ruphenyl)-S-methylisothiourea and glycine (yield: 28%, melting point: 163°C). The sweetening potency of this compound corresponds to approximately 700 times the sweetness of a 2% sucrose solution on an ffiffi basis. Synthesis of N-[N-(S)-α-methylbenzylamino(4-fluorophenylimino)methyl]-2-7minoethanoic acid: This compound was synthesized by the experimental method of Example 2. (S)-α-
Methylbenzyl-N'-(4-fluorophenyl)-
11f from S-methylisothiourea and glycine (
Yield: 15%, melting point: 166°C). The sweetening potency of this compound corresponds to approximately 4000 times the sweetness of a 2% sucrose solution based on ilj 5i. Synthesis of N-[N-(S)-α-methylbenzylamino(4-nitrophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized according to the experimental method described in Example 2. (S)
)-α-methylbenzyl-N'-(4-nitrophenyl)-3-methylisothiourea and glycine (
yield ff 185%, melting point 198°C). The sweetening capacity of this compound is based on heavy h1, 2%
It is approximately 7000 times sweeter than a sucrose solution. Synthesis of N-[N-(S)-α-methylbenzylamino(4-methoxyphenylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by the experimental method of Example 2. )−α−
Methylbenzyl-N'-(4-methoxyphenyl)-8
-obtained from methylisothiourea and glycine (absorbed ff
122%, melting point 195°C). The sweetening potency of this compound corresponds to approximately 2100 times the sweetness of a 2% sucrose solution on a ff1ffi basis. 1151: Synthesis of N-[N-(S)-α-methylbenzylamino(4-hydroxyphenylimino)methyl]-2-7minoethanoic acid: HCH(C113)Cabs (S) This compound is an example (S)-α-methylbenzyl-N′-(4-hydroxyphenyl)-8- by the experimental method described in 2.
Obtained from methylisothio l72M and glycine (yield f
f123%, melting point 160°C). The sweetening potency of this compound corresponds to approximately 400 times the sweetness of a 2% sucrose solution on a 11 basis. 1111: Synthesis of N-[N-(S)-α-methylbenzylamino(4-methylmercaptophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by N-(S) according to the experimental method of Example 2. )−α−
Obtained from methylbenzyl-N'-(4-methylmercaptophenyl)-8-methylisothio urea and glycine (yield 77%, melting point 171°C). The sweetening potency of this compound corresponds to approximately 1200 times the U taste of a 2% sucrose solution on a 1-to-6 basis. Thick itm: Synthesis of N-[N-(S)-α-methylbenzylamino(4-cyano-3-methylphenylimino)methyl]-2-aminoethanoic acid: This compound is N-(S)-α-methyl Benzyl-N'-
Obtained from (4-cyano-3-methylphenyl)-S-methylisothiourea and glycine (yield 46%, melting point 172°C). The sweetening potential of this compound is f[! It corresponds to about 50,000 times the sweetness of a 2% sucrose solution on a fin basis. Tomo1M2UniN-[8-(S)-α-methylbenzylamino(3,4
-dichlorophenylimino)methyl]-2-7minoethanoic acid: (I) This compound was prepared according to the experimental procedure described in Example 2.
Obtained from (S)-α-methylbenzyl-N'-(3,4-dichlorophenyl)-3-methylisothiourea and glycine (yield 20%, melting point 195°C). The sweetening capacity of this compound corresponds to approximately 17,0 OCI of the sweetness of a 2% sucrose solution on a 1@M basis. 1 Blood JL14: Synthesis of N-[N-(S)-α-methylbenzylamino(3-trifluoromethyl-5-methoxyphenylimino)methyl]-2-aminoethanoic acid: This compound was described in Example 2. N-(S
)-α-methylbenzyl-N'-(3-trifluoromethyl-5-methoxyphenyl)-8-methylisothiourea and glycine (yield ω71%, melting point 19
2℃). The 11 flavoring capacity of this compound corresponds to approximately 7,000 times the sweetness of a 2% sucrose solution based on one company. 1: N-(N-(S)-α-methylbenzylamino(3,5
-dimethylphenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2.
S)-α-Methylbenzyl-N′-(3,5-dimethylphenyl)-3-methylisothiourea and glycine (yield 167%, V& point 225°C). The sweetening power of this compound is approximately 30,000 times the taste of a 2% sucrose solution on a weight basis. Tomoko: N-[8-(S)-α-methylbenzylamino(3,5
Synthesis of N-(-dichlorophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2.
S)-α-Memethybenzyl-N'-(3,5-dichlorophenyl)-8-methylisothiourea and glycine (yield 46%, )ii point 202°C). The sweetening capacity of this compound is about 120,000 times the sweetness of a 2% sucrose solution, about 90,000 times the sweetness of a 5% sucrose solution, and about 50 times the sweetness of a 10% sucrose solution on a m1 basis. ,000 times. Shoniwa Blood Uni N-[N-(S)-α-methylbenzylamino(3,5
-Dichloro)Tnylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2.
)-α-Methylbenzyl-N′-(3,5-difluorophenyl)-8-methylisothiourea and glycine (yield 66%, melting point 212°C). The sweetening potency of this compound corresponds to approximately 15,000 times the sweetness of a 2% sucrose solution on a heavy M basis. LLdan: N-(N-(S)-α-methylbenzylamino(3,4
,5-Trichlorophenylimino)methyl 1-2-aminoethanoic acid: j This compound was synthesized using the experimental method described in Example 2.
(S)-α-methylbenzyl-N'-(3,4,5-
Obtained from (trichlorophenyl)-8-methylisothiourea and glycine (yield 69%, melting point 208°C). The sweetening capacity of this compound corresponds to approximately 35.000 times the sweetness of a 2% sucrose solution on a mm basis. Synthesis of apical pentauninide [2-nitro(3,5-dichlorophenylamino)ethynyl]-2-aminoethanoic acid: 1-nitro-2,2-( of CI 5J (301a+01)
methylthio)edene and 4.01 g (30 m mol
) of 3.5=dichloroaniline is mixed with 50 cd of 95% ethanol. The solution is heated with fast flow for 6 hours. After cooling, the formed precipitate was filtered and diluted with ethyl ether (3
Wash with X20cd). 5.3 g of 1-nitro2.
2-(Methylthio)-edene (yield 163%, melting point 114°C) was obtained. CI' 1.34 g (17,91 mol > glycerin, 39
(17,9 imol) of 1-nitro-2-(3
, 5-diphenylamino)-2-(methylthio)edene in 50 cm of a 5:1 solution of water to ethanol.
car (17,91101) of triethylamine. Mix in 2 hours! Drain and heat. After concentration in vacuo, the residue is dissolved in 1N sodium hydroxide 60C11'. The resulting solution was washed with ethyl acetate (4 x 20 cd) and acidified in 5 Nll (J solution to pH 7. The resulting solid was filtered, washed with water (2 x 2 m),
Dry in vacuum. 1.4 g of to[2-nitro(3,5
-dichlorophenylamino)ethynyl]-2-aminoethanoic acid (yield Ei 26%) is obtained with a melting point of 207°C. The sweetening potency of this compound corresponds to approximately 400 times the sweetness of a 2% sucrose solution on a ff1ffi basis. Support: Synthesis of N-[2,2-dicyano(3,5-phenylhumino)ethynyl 1-2-aminoethanoic acid: 1.64
A 50% dispersion of sodium hydride in liquid paraffin No. 9 was cooled to 0°C and 25 ci of dimethylborumamide was added.
2.2647 of malondinitrile dissolved in f (34
m n + ol ) is cooled to 0° C. and added in several portions. The solution is then held at 10°C for 10 minutes. 7 (34+ mol) of 3°5-dichlorophenylisocyanate is dissolved in 20 m dimethylbormamide and added to the solution. The reaction mixture is kept at 20° C. for 15 minutes and then concentrated to dryness. After heating and grinding, the residue is dried under vacuum. 69 solids are obtained in this way, dissolved in 200 d of dimethyl sulfate in 95% ethanol and left in contact for 2 hours at 20°C. After distilling off the ethanol, the remaining solids were washed with 4×50 ct+I water. 4.3g of 1.1-dia2-(3
,5-dichlorophenylamino)-2-(methylthio)
- Eden (yield 74%) is obtained after drying. 1.584? (21,111 mol) of glycine and 49 (21,1 mmol) were added to 2.7 g (21
1 mmol) dissolved in 200 d of ethanol. The mixture is kept at 70°C for 24 hours. Concentrate using vacuum. The residue was dissolved in 2% aqueous sodium carbonate solution.
Dissolve rR in 00cnl. The solution is washed with 3×50 d of ethyl ether and acidified with 3 NIICj solution. iii) The dough-like precipitate is separated by decantation. After purification by chromatography, 0.47 of N-[2,2diano(3,5-dichlorophenylamino)ethynyl]-2-aminoethane was purified by (10
3°C melting point). The sweetening potential of this compound is based on fnffi 2
% sucrose solution. Synthesis of Mitate Edanuni N-[N-methyl-N-benzylamino(3,5-dichlorowainylimino)methyl 1-2-aminoethanoic acid: C! This compound is obtained from N-methyl-N-benzyl-N'-3,5-dichlorophenyl-3-methylisothiourea and glycine by the experimental method described in Example 2.
yield 1110%, melting point 153°C). The sweetening potential of this compound is based on fflgt2
It corresponds to about 20.000 times the sweetness of the % sucrose solution. Inudate M Yu1: N-[N-methyl-N-1-methylethylamino(4-
Synthesis of N-methyl-N-cyanophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by the experimental method of Example 2.
1-Methylethyl-It'-(4-cyanophenyl)-
Obtained from S-methylisothiourea and glycine (yield 5%, melting point 120°C). The sweetening power of this compound (equivalent to approximately 80 times the sweetness of a 2% sucrose solution on a 1-year basis). Synthesis of imino)methyl]-2-aminoethanoic acid:
This compound is obtained from N-nobu-N-benzyl-N'-(4-cyanophenyl)-S-methylisothiourea and glycine by the experimental method described in Example 2.
Aggregation: 22%, melting point: 133°C). The sweetening properties of this compound are approximately 3,000 times as sweet as a 2% sucrose solution, approximately 1,800 times as sweet as a 5% sucrose solution, and 1:1 as sweet as a 10% sucrose solution on a weight basis. It is equivalent to about 1,200 times the taste. Shakutate block A: Synthesis of N-[N-ethyl-N-benzylamino(4-cyanophenylimino)methyl]-2-aminoethanoic acid:
This compound was prepared using N-ethyl-N-
Obtained from benzyl-N'-(4-cyanophenyl)-methylisothiourea and glycine (yield 5%, freshwater fish 1
47℃). The sweetening potency of this compound is approximately 3,000 times as sweet as a 2% sucrose solution on a fJfffl basis. Supporter: N-[N-ethylamino (4-cyanophenylimino)
Synthesis of methyl 1-2-aminoethanoic acid: This compound was synthesized as N-ethyl-N'-(4-
Cyanophenyl>-S-methylinch A 19 is prepared from urea and glycine (yield: 118%, melting point: 185°C). The sweetening potency of this compound corresponds to approximately 350 times the sweetness of a 2% sucrose solution on an IB basis. Synthesis of N-I N-hexylamino(4-cyanophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized from N-hexyl-N by the experimental method described in Example 2.
'-(4-cyanophenyl>-obtained from S-methylisothiourea and glycine (yield: 17%, melting point: 159℃)
). The sweetening capacity of this compound is approximately 6,000 times as sweet as a 2% sucrose solution, approximately 4,300 times as sweet as a 5% sucrose solution, and approximately 1 times as sweet as a 10% sucrose solution on a weight basis. ,400 times. Synthesis of N-(N-(3-methylbutyl)amino(4-cyanophenylimino)methyl 1-2-aminoethanoic acid:
This compound is obtained from (3-methylbutyl)-N'-(4-cyanophenyl)-8-methylisothiourea and glycine according to the experimental method of Example 2 (yield 116%, melting point 192 DEG C.). The sweetening capacity of this compound is approximately 200 times as sweet on a weight basis as a 2% sucrose solution. Accident: N-[N-(1,1-dimethylpropyl)amino(4-
Synthesis of N-(1,1-dimethylpropyl)-N'-(4-cyanophenyl) according to the experimental method of Example 2.
IJ is produced from -S-methyisodiourea and glycine (yield: 116%, melting point: 210°C). The sweetening capacity of this compound is approximately 300 times as sweet on a weight basis as a 2% sucrose solution. Synthesis of 1-difference (1 UniN-(N-(1,1,3,3-tetramethylbutyl)amino(4-cyanophenylimino)methyl 1-2-aminoethanoic acid: h, ,C(CsλCH2CCC ?(3)3 This compound was prepared as N-(1,1,3
, 3-Tetramethylbutyl) -N'-(4-cyanophenyl>-S-Methylisothiourea) obtained from glycine (yield 43%, melting point 189°C). The sweetening potency of this compound is 1!: 2% based on m@m
It is approximately 1,200 times sweeter than a sucrose solution. Matatego A Emperor: N-[N-phenylamino(phenylimino)methyl 1
-2-aminoethanoic acid combination@: This compound was synthesized by N, according to the experimental example described in Example 2.
Obtained from N'-diphenyl-8-methylisothiourea and glycine (yield: 141%, 9m point, 214°C). The sweetening capacity of this compound is 2% when lff1 is 11.
It corresponds to about 500 sweetness of sucrose solution. Synthesis of to[tophenylamino(4-cyanophenylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2 tocyclononyl-N'-
Obtained from (4-cyanophenyl)-8-methylisothiourea and glycine (yield: 133%, melting point: 142°C)
). The sweetening capacity of this compound is equivalent to approximately 4,00018 of the sweetness of a 2% sucrose solution on a weight basis;
This corresponds to approximately 650 times with respect to sucrose solution. Synthesis of uni-N-[N-cyclohexylamino(phenylimino)methyl]-2-aminoethanoic acid: 1st step 2N-cyclohexyl-N'-phenylcarbodiimide 2.09
(8.55 mmol) of N-cyclohexylphenylthiourea, 2.9 g (11°1 mmol) of triphenylbosphine and 1.16 at (12+n mol)
) in methylene chloride 12Crn' was mixed with triethylamine 1°19d (8.55m
mol). The solution is heated for 2 hours, the precipitate that forms is removed by filtration, and the solution is concentrated to dryness. The obtained residue was extracted with hexane,
Therefore, filter it. Therefore, the desired carbodiimide is obtained in the form of an oil by concentrating the solution for drying. 2nd step: Synthesis of N-[8-cyclohexylamino(phenylimino)methyl]-2-aminoethanoic acid: 1,6
g (8 mmol) of the already obtained compound and 1.3
A suspension of 4 g (81 mol) of glycine t-butyl ester hydrochloride in 20 d of acenitrile is centrifugally heated for 12 hours. The resulting solution is then concentrated to dryness in vacuo and the residue is triturated in ethyl ether. Solid t-butyl N-[N
-cyclohexylamino(]1nylimino)methyl 1-
2-aminoethanoic acid ester is obtained. A stirred solution of 2 g (5,45 mmol) of the compound already obtained in 8 cni acetic acid was added to dioxane to form 6.988 cm' of H (7.8 cm' (54,4 mmol) of J).
. 1) was reacted for 1 hour at 20°C. Concentrate in vacuum for drying. The residue is triturated with ethyl ether. Desired compound 1.69 in the form of Salt M salt (yield 19
4%, point a 160-165°C). The sweetening capacity of this compound is 2% based on mff1.
It is approximately 100 times sweeter than a sucrose solution. Synthesis of uni-N-[N-cyclohexylamino(4-cyanophenylimino)methyl 1-2-aminoethanoic acid: 11(
- Negative H'l+ This compound is obtained from N-cyclohexyl-N'-(4-cyanophenyl-S-methylisothiourea and glycine by the experimental method described in Example 2.
58%, melting point 214°C). The sweetening capacity of this compound is approximately 12,000 times the sweetness of sucrose for a 2% sucrose solution on a heavy electric basis.
10.500 times for the 5% sucrose solution and 8,500 times for the 10% sucrose solution. Mitate #iA: Synthesis of N-[N-cyclohebutylamino(3,5-dichlorophenylimino)methyl]-2-aminoethanoic acid:
This compound was prepared as N-cyclohebutyl-N'-(3,5-dichlorophenyl) by the experimental method described in Example 2.
Obtained from -8-methylisothiourea and glycine (
yield ff 187%, melting point 202°C). The U law ability of this compound is 2% based on ff1l.
Approximately 1 in 20,000 of the sweetness of a sucrose solution. Shinodan A ball: Synthesis of N-(N-cyclohebutylamino(4-cyanophenylimino)methyl)-2-aminoethanoic acid: The sweetness of this compound was determined by the experimental method described in Example 2. The capacity of the material is equivalent to approximately 60,000 of the sweetness of a 2% sucrose solution based on mold opening.

[Synthesis of octylamino(3,5-dichlorophenylimino)methyl 1-2-aminoethanoic acid: I This compound was synthesized by the experimental method described in Example 2. )
Obtained from -8-methylisothiourea and glycine (
Condensation: 61%, @ point: 199°C). The ability of this compound chemical law is based on ff1fa and is 2
% of the sweetness of the sucrose solution. 3t! Synthesis of fLLuni-N-[N-cyclooctylamino(4-cyanophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2 tosicOoctyl-N'-(4- Obtained from cyanophenyl)-8-methylisothiourea and glycine (yield frt 80%,
melting point 228°C). The sodium or potassium salt of a compound is one of the compounds
g is dissolved in 3 cmff of 1N sodium hydroxide solution and concentrated for drying. The sweetening capacity of this compound is equivalent to approximately 170,000 of the sweetness of a 2% sucrose solution on a weight 8 basis;
This corresponds to a factor of 130,000 for the sucrose solution and a factor of 100.000 for the 10% sucrose solution. Synthesis of A1 nido[tocyclooctylamino(4-cyano-3-methylphenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized as N-cyclooctylaminoN'- by the experimental method described in Example 2. Obtained from (4-cyano-3-methylphenyl)-8-methylisothiourea and glycine (yield: 130%, F11 point: 155°C). The sweetening capacity of this compound is equivalent to approximately 80,000 11 tastes of a 2% sucrose solution on a m0 basis. On Firedust A: N-[N-cyclooctylamino(3-chloro-4-cyanophenylimino)methyl 1-2-aminoethanoic acid This compound was synthesized from N-cyclooctyl-N by the experimental method described in Example 2. '-(3-chloro-4-cyanophenyl)
Obtained from -8-methylisothiourea and glycine (
yield ff 168%, melting point 156°C). The sweetening potency of this compound is approximately 100,000 times greater than the 2% suc C]-su11 (7) sweetness +7) based on @M. Synthesis of N-[tocyclononylamino(4-cyanophenylimino)methyl]-2-7minoethanoic acid: This compound was synthesized as tocyclononyl-N'-(4 -cyanophenyl)-8-methylisothiourea and glycine 1! ? (yield 70%, melting point 1
95℃). The sweetening potency of this compound is approximately 200,000 times as sweet as a 2% sucrose solution on a per unit basis. Synthesis of Nido[tobenzylamino(3,5-dichlorophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2.
'-(3,5-dichlorophenyl)-8-methylisothiourea and glycine (yield 35% 1m point 1
82℃). The sweetening power of this compound is based on 2ffi, 2
% sucrose solution, about 80,000 times as much. Synthesis of N-[N-benzylamino(4-cyanophenylimino)mebul 1-2-aminoethanoic acid: HC1bQ
H5 This compound was prepared by the experimental method described in Example 2.
19 is prepared from benzyl-N'-(4-cyanophenyl)-8-methylisothiourea and glycine (yield 31%).
, melting point 149°C). The sweetening potency of this compound is approximately 30,000 times sweeter on a weight basis compared to the sweetness of a 2% sucrose solution;
27,000 times the sweetness of a 10% sucrose solution, and approximately 22,00 times the sweetness of a 10% sucrose solution.
Corresponds to 0 times. Synthesis of Tomokagoritachi Uni N-(N-phenylethylamino(4-cyanophenylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by N-phenylethyl-N' by the experimental method described in Example 2. -(4-cyanophenyl) -19 produced from -S-methylisothiourea and glycine (yield: 52
%, melting point 129°C). The sweetening capacity of this compound is approximately 8.50% of the sweetness of sucrose on a 2% sucrose solution on a weight basis.
equivalent to approximately 6,100 times for a 5% sucrose solution.
times, corresponding to approximately 4,200 times with respect to the 10% sucrose solution. Mitate Alliance A: N-[N-(R)-α-methylbenzylamino(4-
Synthesis of cyanophenylimino)methyl]-2-aminoethanoic acid: It CH(CH3)C6Hs (R) This compound was synthesized as N-(R) by the experimental method described in Example 2.
-α-Methylbenzyl-N'-(4-cyanophenyl)-3-methylisothiourea and glycine [recovery 71%; (α) D''-112,5'
(C=1, 0.5N H(J), melting point 189°C]. The sweetening capacity of this compound is approximately 9,000 times the sweetness of sucrose for a 2% sucrose solution on a weight-by-weight basis.
equivalent to approximately 6.600 times for a 5% sucrose solution
times, which corresponds to approximately 2.500 times for a 10% sucrose solution. Synthesis of N-[N-cyclohexylmethylamino(phenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized as N-cyclohexylmethyl-N by the experimental method described in Example 2. Obtained from '-phenyl-5-methylisothiourea and glycine (yield 133%, melting point 185
℃). The sweetening potency of this compound is approximately 3.30% of the sweetness of sucrose for a 2% sucrose solution on a single basis.
equivalent to approximately 2,500 times for a 5% sucrose solution.
times, corresponding to approximately 2.000 times with respect to the 10% sucrose solution. Tip ■5: Synthesis of N-[N-cyclohexylmethylamino(3-cyanophenylimino)methyl 1-2-aminoethanoic acid: It , CH2CbHr') \, l C 1st step: N-(3 -cyanophenyl) -N'-t-
Butyoxycarbonyldiourea: 2,8 cnr (20111 mol) of triethylamine and 3,2 g (20 mmol) of 3-cyanophenyl isocyanate were mixed in 150 d of dichloromethane at 0° C. with 3.35 g of glycine t-butyl ester ( 2
Add 0mn+ol) to the solution. The mixture is stirred at 20° C. for 12 hours before being concentrated in vacuo. Extract with a mixture of water and ethyl needle (300:300). The ether phase is separated and washed with 1N hydrochloric acid solution (200 Cd). Then, it is washed with a saturated saline solution. After drying with magnesium sulfate, it is subjected to rA condensation under reduced pressure. melting aGj131-132℃F5,179 (
A yellow solid of 89% yield is obtained. Second step Nido[N-cyclohexylmethylamino(3-
Synthesis of cyanophenylimino)methyl 1-2-aminoethanoic acid: 2.23 tJ (10,82 mmol) of dicyclohexylcarbodiimide and 1.4 cd (1,1 mol) of cyclohexylmethylamine in 70 crt of ethyl ether. of the above thiourea (10,3ma+ol
) to the solution. The mixture is heated centrifugally in a nitrogen atmosphere for 72 hours. It is then concentrated to 20Cr&. The resulting solids are cooled and removed by filtration, and the liquid is concentrated under vacuum. The oil obtained is purified by chromatography on silica gel. (Eluent: 5:95 methanol:ethyl acetate) 2.0
7 g (54% yield) of pale yellow oil are obtained. The thus obtained 0.4 g (1.08 i mol
) was dissolved in 1.6cd of pure acetic acid and 1,6cd of 6.82H hydrogen chloride in dioxane.
d (10.81 mmol) was added dropwise to the processed tc solution and allowed to react. After holding at 1 m for 2 hours, the solution was concentrated in vacuo and the resulting oil was dissolved in ethyl ether with 100 c? 1
24 hours and released. After 1 filtration, 0.31
g (82% yield, melting point 80-83°C) of the desired compound is obtained in the form of the hydrochloride salt. The sweetening capacity of this compound is equivalent to approximately 5.000 times the sweetness of a 2% sucrose solution on a weight basis. Synthesis of real [: N-[It-cyclohexylmethylamino(3,5-dichlorophenylimino)methyl]-2-aminoethane: (! This compound was synthesized as N-cyclohexylmethyl by the experimental method described in Example 2. -N'-(3,5-:)-O-lovinyl>-S-Methylisothiourea and glycine (50% condensation, melting point 186°C).The sweetening ability of this compound is On a basis, it corresponds to about 35,000 times as much as a 2% sucrose solution.Synthesis of N-[N-cyclohexylmethylamino(4-chlorophenylimino)methyl]-2-aminoethanoic acid: 11 Cll 2 QJ(++ This compound was prepared as N-cyclohexylmethyl-N'-(4-chlorophenyl) by the experimental method described in Example 2.
Obtained from -8-methylisothiourea and glycine (
Yield 33%, melting point 183°C). The sweetening potency of this compound is approximately 3 times as sweet as sucrose for a 2% sucrose solution, based on nFtl.
, 500 times, and about 2 for a 5% sucrose solution.
,700 times, about 1,5 with respect to 10% 0% sulfur
This corresponds to 00 times. Backyard ■ Synthesis of five uni N-[,N-cyclohexylmethylamino(4-cyanophenylimino)methyl J-2-aminoethanoic acid: This compound was prepared as N-cyclohexyl according to the experimental method described in Example 2. Methyl-N'-(4-cyanophenyl)
Obtained from -3-methylisothiourea and glycine (
yield ff 148%, melting point 180°C). The sweetening capacity of this compound is approximately 35,000% of the sweetness of sucrose on a 2% sucrose solution on a weight basis.
0 times, approximately 28.0 for 5% sucrose solution
00x, approximately 17.00 for a 10% sucrose solution
Corresponds to 0 times. χTachi M Engineering: Synthesis of N-[N-cyclohexylmethylamino(4-methoxycarbonylphenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized as N-cyclohexyl by the experimental method described in Example 2. Obtained from ethyl-N'-(4-methoxycarbonylphenyl)-8-methylisothiourea and glycine (yield f [157%, melting point 182°C), the sweetening capacity of this compound is 2% on a weight basis. This corresponds to approximately 1.300 times the 11 taste of sucrose for a sucrose solution, approximately 900 times the taste of sucrose for a 5% sucrose solution, and 10
% sucrose solution. Synthesis of Tomogogouni N-[N-cyclohexylmethylamino(4-carboxyphenylimino)methyl J-2-aminoethanoic acid: This compound was synthesized in 1N sodium hydroxide solution with a melting point of 163°C. Saponification of tocyclohexylmethylamino(4-carboxyphenylimino)methyl 1-2-7minoethanoic acid (79% yield, F! & 16 points)
4℃). The former is obtained from N-cyclohexylmethyl-N'-(4-methoxycarbonylphenyl)-8-methylisothiourea and glycine by the experimental method described in Example 2. The sweetening potency of this compound is approximately 50 times the sweetness of a 2% sucrose solution on a weight basis. Bakuo ■11: Synthesis of N-[N-cyclohexylmethylamino(4-nitrophenylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized as N-cyclohexylmethyl- by the experimental method described in Example 2. N'-(4-nitrophenyl)
Obtained from -8-methylisothiourea and glycine (
Yield 39%, melting point 203°C). The sweetening potency of this compound is approximately 8.000 times the sweetness of sucrose for a 2% sucrose solution, based on
equivalent to approximately 7.500 times for a 5% sucrose solution
times, corresponding to approximately 4,000 times for the 10% sucrose solution. 11 Gotouni N-[N-(S)-1-cyclohexylethylamino (
Synthesis of 3°5-dichlorophenylimino)methyl 1-2-aminoethanoic acid:
S)-1-cyclohexylethyl-N'-(3,5-
Obtained from dichlorophenyl)-8-methylisothiourea and glycine. (Yield 1 m 80%, melting point 150°C) The sweetening capacity of this compound corresponds, on a weight basis, to approximately 70.000 times the sweetness of a 2% sucrose solution. Backyard Dish IA: Synthesis of N-(N-(2-methylphenyl)amino(4-cyanophenylmethyl)-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2. methylphenyl) -N' -(4-cyanophenyl)-8
- Obtained from methylisothiourea and glycine. (Yield 69%, melting point 165°C). The sweetening capacity of this compound is 2% on a weight basis.
It corresponds to about 5,000 times the sweetness of sucrose solution. Synthesis of N-[N-(3-methylphenyl)amino(4-sialaf1nylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2. −
methylphenyl) -N' -(4-cyanophenyl)
Obtained from -8-methylisothiourea and glycine. (Yield 69%, melting point 220°C). What is the sweetening power of this compound? 4! Based on the 2
% sucrose solution is approximately 9,000 times sweeter. Synthesis of N-(N'-(4-methylphenyl)amino(4-cyanophenylimino)methyl)-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2. (
4-methylphenyl), -N'-(4-cyanophenyl)-8-methylisothiourea and glycine. (Yield 145%, point a 216°C). The sweetening capacity of this compound is 2% based on ill.
It is approximately 7,000 times sweeter than a sucrose solution. Synthesis of N-[N-(1-methylcyclohexylethyl)amino(4-cyanophenylimino)methyl]-2-aminoethanoic acid: 1st step: N-(1-methylcyclohexyl)-N '
-(4-Cyanophenyl)thiourea: A solution of 10.269 (64,0511101) 4-cyanophenyldioisocyanate in 250 d of ethyl acetate was cooled to 0°C, and 1-methylcyclohexyl 7.59 g (67.1 mmo
l). The solution is stirred at room temperature overnight. The precipitate formed is filtered and washed in ethyl ether. There, the liquid is vacuumed and concentrated for drying. The residue is triturated with 50 crl of ethyl ether to obtain a second portion of thiourea. 14.439 (yield ff 182.5%) of the desired thiourea are obtained in total. 2nd step: N-(N-(1-methylcyclohexyl)
Synthesis of amino(4-cyanophenylimino)methyl]-2-aminoethanoic acid 1.399 (5,08 m5ol) of nido(1-methylcyclohexyl)-N'-(4-cyanophenyl)thiourea
), glycine [-butylnisder 1g (7゜5311
101) and 0.05 cm (0,34
mmol) in 10C1I of ethyl ether and stirred at room temperature for 4 hours. The dicyclohexylthiourea produced is removed by filtration, and the liquid is concentrated for drying. The resulting residue was chromatographed [1]. Using a tower with a diameter of 50 m, 0.6%
C112C1x-CI1301 containing NH4011
It eluted with 1955/C112C1z. Therefore, it is recrystallized using hexane. 1.43g (Yield 1
76%) of butylt[t(1-methylcyclohexyl)]
Amino(4-cyanophenylimino)medel]-2-aminoethanoic acid is obtained. 6.98N in 3.807 acetic acid and diquaternary nitrogen
(13 mmol) 1.9 of a solution with 1Icf
0.5y (1,35m
mo! ) mixed with The solution was stirred for 40 min,
The reaction is continued by adding 0 d of ethyl ether to promote the formation of a crystallized oil after several hours of stirring. solid)
Filter and wash with ethyl ether. After drying, 0.4259 (several times 90%) of the desired compound was obtained. 3rd step: Synthesis of N-[N-(1-methylcyclohexyl)amino(4-cyanophenylimino)methyl 1-2-aminoethane wave: in the water-methanol (25-5) mixture in the Tate step. 0.508g (1°451
1111101) in 0°4 of sodium hydroxide.
Mix with 75 g (11,91+1101 > of the solution) and filter the methanol in vacuo. The solution was made p! by adding 10% hydrogen chloride solution. Neutralize to 17. After that - after stirring at night, one house is served. 0.31 g (68% yield) of the desired product was obtained (7%). The sweetening capacity of this compound corresponds to about 100 times the 14 taste of a 2% sucrose solution on a !S basis. N-I N-1-naphthylamino (3,5-dichlorophenylamino) This compound was used in the experimental procedure described in Example 2.
1-S7%ruN'-(3,5-SchiffD07enyl)-S'-Methylthiourea and glycine. (Yield 78%, melting point 210°C). The sweetening potency of this compound is approximately 30,000 times sweeter than a 2% sucrose solution, based on ff1ffi. Synthesis of N-[N-1-naphthylamino(4-cyanophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized using the experimental method described in Example 2. Obtained from naphthyl-N'-(4-cyanophenyl)-8-methylisothiourea and glycine. (Yield 44% 1m point 178°C). The sweetening capacity of this compound corresponds, on a weight basis, to approximately 60.000 times the sweetness of a 2% sucrose solution. Synthesis of N-[8-(1-indanyl)amino(4-cyanophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2.
-indanyl) -N' -(4-cyanophenyl)-
Obtained from 8-methylisothiourea and glycine. (
Yield (n62%, melting point 176°C). The sweetening capacity of this compound is approximately 5,000 times as sweet on a weight basis as a 2% sucrose solution. Synthesis of Omotesuki IL Uni-N-(8-(1-adamantyl)amino(4-cyanophenylimino)methyl)-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2.
adamantyl)-N'-(4-cyanophenyl)-5-
Obtained from methylisothiourea and glycine (yield 5
5%, melting point 232°C). The sweetening ability of this compound is based on lff1, 2
% sucrose solution is approximately 3,500 times sweeter. Synthesis of N-[8-(1-7 damantylmethyl)amino(4-cyanophenylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2. −
Obtained from 7-damantylmethyl)-N'-(4-cyanophenyl)-8-methylisothiourea and glycine (yield 62%, melting point 169°C). The sweetening capacity of this compound is equivalent to approximately 23,000 times the sweetness of a 2% sucrose solution on a mm basis. Tip 1 ■ Synthesis of uninide [cyanoimino(3-chlorophenylamino)methyl 1-2-aminoethanoic acid: 0M 109 (59i+mol) of 3-chlorophenylisothiocyanate and 4.159 (65++ mol)
) of monosodium cyanamide is mixed with 100 cm of absolute ethanol and boiled for 2 hours. After the solvent was distilled off, the solid residue formed was washed with 100 cm of ethyl ether. The compound was prepared by adding 4.8 cd (771101) of methyl iodide to 50.5 cd of ethanol. Suspend in a solution of CD. The mixture is then heated at room temperature for 20 hours, and the ri precipitate is filtered and washed with water (2X 50 car) and ethanol (2X 50 cd). Vacuum and dry. 10.19 of tri(3-O-lophenyl)-N'-cyano-8-methylthiourea having a melting point of 167°C. N 3g (39,9a + mol) of glycine and 1.55F
(37,211101) of sodium hydroxide and water of 1
Mixed with 0CIII, 6g (26,5a+a+ol
) of (3-chlorophenyl)-N'-cyano-8-
Add to a solution of methylisothiourea in 40 cd of 95% ethanol. The mixture is centrifugally heated for 1 hour. After cooling, the precipitate formed is filtered and washed there with 2×50 d of ethyl ether. 1N of the generated solid
Dissolve in 50 cuts of sodium hydroxide solution. This solution was washed with 3×10c11 dichloromethane,
Acidify with 3N 11CI until p■ approaches 2. The resulting white solid is filtered, washed with 2×10 cm of water and dried in vacuo. 6 g of tho[cyanoimino(3-ri00phenylamino)methyl]-2-aminoethanoic acid having a melting point of 109°C (yield: 189
%) is obtained. The sweetening capacity of this compound is based on fli, 2%
It is approximately 80 times sweeter than a sucrose solution. Synthesis of N-[tho(N-methyltophenylamino)(4-cyanophenylimino)methyl]-2-7minoethanoic acid: This compound was synthesized by the experimental method described in Example 2. −(
N-methyl-N-phenylamino) -N' -(4-
Obtained from cyanophenyl)-8-methylisothiourea and glycine (yield: 113%, melting point: 202°C), the sweetening capacity of this compound is approximately 18,000 times as sweet as a 2% sucrose solution on a l basis. do. Synthesis of N-[N-(3,4-methylenedioxyphenyl)amine(4-cyanophenylimino)methyl]-2-amineethanoic acid: This compound was described in Example 2. N-( by experimental method
Obtained from 3,4-methylenedioxyphenyl)-N'-(4-cyanophenylimino)-3-methylisothiourea and glycine (yield 110%, melting point 166°C)
. The sweetening capacity of this compound is equivalent to approximately 5,000 (8) of the sweetness of a 2% sucrose solution on a weight basis. This compound was prepared by the experimental method described in Example 2.
-obtained from methylisothiourea and glycine (yield 20%, melting point 215°C). The sweetening capacity of this compound is based on El (selected, 2%
It is approximately 500 times sweeter than a sucrose solution. Pigeon JLLヱ: N-[N-morpholinoamino(4-cyanophenyl) This compound was prepared from tomorpholino N'-(4-cyanophenyl)-S-methyisodiourea and glycine by the experimental method described in Example 2. obtained (Il 119
(+, FX'i point 205°C). The sweetening capacity of this compound is equivalent to approximately 950 moles of the sweetness of a 2% sucrose solution on a weight basis. Synthesis of N-[N-(2,2,4,4,tetramethylcyclobut-3-yl)amino(4-cyanophenylimino)methyl 1-2-7minoethanoic acid: This compound is N-(
2,2,4,4,tetramethylcyclobutol-3-yl)
-N'-(4-cyanophenyl)-8-methylisothiourea and glycine (yield 50%, melting point 2
37℃). The sweetening capacity of this compound is equivalent to approximately 700 times the sweetness of a 2% sucrose solution on a mm basis. Yosha JLL Dan: Synthesis of N-[phenylsulfonylimino(3-chlorophenylamino)methyl]-2-aminoethanoic acid: 5OZ
C61 (5 x 64? (35,4 mmol) of 3-chlorophenylisodiocyanate and 6.1 G (38,9 mmol)
ol) benzenesulfamide and dissolved in 50d acetone. 1.559 (38.9 mmol) of sodium hydroxide is dissolved in 3 Cvi of water and the two solutions are mixed together. The mixture is kept at room temperature for 2 hours. The formed precipitate was filtered and mixed with acetone and ethyl ether (
2.times.20Cr+f) to give 11.3 g of residue (100% yield). This residue was dissolved in 2.88 cnr of methyl iodide (46 I) in 5 Oct/95% ethanol.
Dissolve in a solution containing 1 mol). After standing at room temperature for 24 hours, the solution is exposed to black light to dry. The residue is then washed with ethyl ether (3×20d) and dried under vacuum. 8.75 g of tho(3-chlorophenyl)-N'-phenylsulfonyl-8-methylisothiourea having a melting point of 116 DEG C. are obtained. I 2.3 g parts (30.7 mmol) of glycine and 1
, 157 (28,6 mmof) of sodium hydroxide dissolved in 10 Ctl' of water and 6.4 g (2
0°5 mmol) of N-(3-chlorophenyl)-N'
-phenylsulfonyl-8-methylisothiourea and 5
Mix in 0d of 95% ethanol. mix 9
Time rapid flow heating. The residue obtained in this way is dissolved in 50 ad of 1N sodium hydroxide solution. The solution was mixed with dichloromethane (3X20cd) and ethyl acetate (2X
20ci+? ) and acidified by adding 6N hydrogen chloride solution to pH 3. After cooling, the precipitate formed is filtered and washed with 2×5 Crt water. Next, vacuum dry. 5.6 g of trifersulfonylimino (melting point 218°C)
3-chlorophenylimino)methyl]-2-aminoethanoic acid is obtained (75% yield). The sweetening power of this compound is approximately 17,000 times the sweetness of a 2% sucrose solution on a single needle basis. Xi Shidanko: Synthesis of N-[N-(3-chlorophenyl)amine(4-cyanophenylimino)methyl]-2-aminoethanoic acid: N-(3
-chlorophenyl)-N'-(4-cya/7enylimino)-8-methylisothiourea and glycine (yield: 189%, #11 point: 198°C). The sweetening capacity of this compound is approximately 10,000 times the sweetening power of a 2% sucrose solution on a mm basis. MarutatemeidanuniN-[N-3,5-dichlorophenylamino(3,5-
Synthesis of dichlorophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2.
' -bis(3,5-dichlorophenyl) -3-
It is prepared from methylisothiourea and glycine (yield 35%, melting point 177°C). The sweetening capacity of this compound corresponds to approximately 1.000 times the sweetness of a 2% sucrose solution on a m1 basis. Dog i ■ 1λ: N-[N,N-(tetramethylene)amino(4-cyanophenylimino)methyl]-2-aminoethanoic acid first
Step Synthesis of nido(4-cyanophenylimino)-N'-t-butyloxylponylmethylurea: 10.79 (
821mof) glycine t-butyl ester and 13
g (82 mmol) of 4-cyanophenyl isodithiocyanate are added to a solution of 100 d of acetonyl. After stirring for 12 hours, the formed precipitate was separated and washed with ethyl ether to remove 1 of the desired thiourea.
Obtain 8.7 g (78% yield). 2nd step: Production of N-4-cyanophenyl-N'-t-butyloxyluponylmedy-S-methylthiourea: 2.6 g (8.9 mmol) of the above thiourea and 5
1.6 g of methyl iodide in 0 cm11' of acetone
A mixture of (11,1 mlof) is stirred at 20°C for 12 hours. The mixture is dried and the residue is filtered and triturated in ethyl ether. The iodide obtained is dissolved in 1N sodium hydroxide solution and the mixture is extracted with dichloromethane. After drying with anhydrous sodium hydroxide and concentrating for drying, 2.3f
f (Yield ff 182%) The desired compound is obtained. Third step: N-[8,N-(tetramethylene)amino(
Preparation of hydrochloride of 4-cyanophenylimino)methyl-2-aminoethanoic acid: 6.5 g (21 mmol) of the above compound and 2.62
cd (31m mol) throat lolidine 100cm
of the same amount dissolved in absolute ethanol and heated to 0° C. for 24 hours. Add 1.3 cm (15 mmol) of throat lolidine again and continue to heat for an additional 1/IIF. The reaction mixture is concentrated to dryness in vacuo and the residue is chromatographed using a column of silica gel (eluent: 92° 5:0.5 methanol:dichloromethane:ammonium hydroxide). 2.8g
(Yield: 40%) [-butyl ester of N-[N,N-(tetramethylene)-amino(4-cyanophenylimino)methyl]-2-aminoethanoic acid is obtained. 1 g (3.13 mmo) of the above ester to 11 cd of acetic acid
A solution of 4°5d of 1Icj of 6.98H in dioxane is stirred for 1 hour. The reaction mixture is poured into 1 liter of ethyl ether. The produced precipitate is separated by furnace, dissolved in water, and 1 g of the solution is freeze-dried. 0.669 (yield: 66%) of the desired compound is obtained with the addition of basic acid. The sweetening potency of this compound is approximately 100 times the sweetness of a 2% sucrose solution on an m mother basis. YoIL Midan: 2. of N-[N,N-(pentamethylene)amino(4-cyanophenylimino)methyl]-2-aminoethanoic acid.
91 g (10 mmol) of N-(4-cyanophenyl)-N'-butyroxycarbonylmethylthiourea,
A mixture of 2.3 g (11 ml 1101) of dichlorohexylcarbodiimide in 50 crl of ethyl ether and 2 cn/(20 mmol) of piperidine is heated at 50° C. for 24 hours. After cold JJI, the dicyclohexylthiourea is removed and the solution is concentrated to dryness under reduced pressure. 4 g of colored oil was purified on a column of silica gel (7.5:92.5 methanol:dichloromethane) and then purified with 1 g (33% yield) of N
The t-butyl ester of -[N,N-(pentamethylene)amino(4-cyanophenylimino)methyl]-2-aminoethanoic acid is obtained. After removing the t-butyl protecting group by the method previously described, 0.71! of the desired compound in the form of the hydrochloride!
? (yield ff195%). The sweetening power of this compound is approximately 200 times the sweetness of a 2% sucrose solution, based on its richness. Song Yu IEL: Synthesis of N-E pendelimino(tomethyl-N-phenylamino)methyl]-2-aminoethanoic acid: Cl12C6
t(5) This compound is prepared from N-benzyl-N-methyl-N-phenyl-3-methylisothiourea and glycine by the experimental method described in Example 2 (yield: 813%, melting point: 138°C). The sweetening capacity of the compound is equivalent to approximately 200 times the sweetness of a 2% sucrose solution on a mm basis. ) Synthesis of methyl]-2-aminoethanoic acid: This compound is obtained from tocyclohexyl-N'-(4-cyanophenyl)-8-methylisothiourea and 0-alanine by the experimental method described in Example 2. (Yield 1
5%, melting point 177°C). The sweetening capacity of this compound is approximately 100 times the sweetness of a 2% sucrose solution on a weight basis. Song 11 (1 interaction: Synthesis of (R)-N-[8-(S)-α-methylbenzylamino(3゜5-dichlorophenylimino)methyl 1-2-aminopropionic acid: This compound was described in Example 2. (S) according to the experimental method described
Obtained from -α-methylbenzyl-N'-(3,5-dichlorophenyl)-8-methylisothiourea and D-alanine (yield 1177%, melting point 177°C). The sweetening capacity of this compound corresponds, on a weight basis, to approximately 120 units of the sweetness of a 2% sucrose solution. Actual date 1. Synthesis of (R)-to[tocyclooctylamine(4-cyanophenylimino)methyl]-2-aminoethanoic acid: This compound was synthesized by tocyclooctyl-N'-(4 -cyanophenyl)-S-methylisothiourea and D-alanine
170%, FJII point 144°C). The sweetening power of this compound is approximately 900 times the sweetness of a 2% sucrose solution on a weight basis. Base 1: Synthesis of N-[8-methyl-N-benzylamino(3,5-dimethylphenylimino)methyl 1-2-aminoethanoic acid: This compound was synthesized by the experimental method described in Example 2. Obtained from dilutebenzyl-N'-(3,5-dimethylphenyl)-8-methylisothiourea and glycine (yield: 122%, melting point: 141°C). The sweetening power of this compound is based on 1ffi, 2
% sucrose solution is approximately 5.000 times sweeter. Table 1 lists the compounds synthesized in Examples 1 to 88 and shows equivalent sweetness potency compared to a 2% sucrose solution. It has been found that these sweeteners of the invention have increased thermal stability when R1 is CH3 instead of a hydrogen atom. As an illustration, the stability of three Lt flavors according to the invention was evaluated at 70° C. and 1 mH of phosphate buffer at p113. The unaffected sweetener concentration was determined by IIPLc. After 6 days under these conditions Example 14 (X4-CN, X3.Xs, R+, R3, R4=Il; A=N
In contrast, after 7 days under the same conditions 50% of the sweetener of Example 31 (X3.
Xa, 113. R4=tl
;A=N: It, = C113 and R2=
At CC11zc) 88% of the sweetener remained unchanged. Similarly, Example 33 (X4=CN, X3.
X5. R3, L=II: A=N and R
, = CH3 and R2 = CIIzCcRs) after 7 days 86% of the sweetener remained unchanged. Furthermore, it is expected that the flavoring agents of the present invention will have improved stability properties when R3 is selected from the group consisting of c, -c3 alkyl groups. The presence of other moieties than H at the R3 position would sterically hinder the cyclization of the molecule and avoid the formation of intermediates that would inactivate the molecule's potential as a sweetener. Numerous flavor and sweetener compositions are contemplated by the present invention, and the invention is not limited to the particular embodiments described herein. Applicant Université Claude Bernard Lyon 1 Procedural amendment (0 phantom July 10, 1988 Patent Application No. 88572 2, Title of invention High potency sweetener 3, Relationship with the case of the person making the amendment Patent application Contents of amendment in each column 6 of "Detailed Description of the Invention" - Amend the "Claims" of the specification as shown in the attached sheet. - Line break after r C+sJ in line IO on page 20 of the specification. Engraving (no change in content) Claim 15 A sweetener represented by the following general formula and containing its tautomeric forms and physiologically acceptable salts thereof: where Xa, X- and X, are the same or different and are selected from the group consisting of the groups shown below, H, Br, CFs, CFtCFs, CHtCFs. alkyl of c, -c, C) I=NOCI-1,
Cl-10, CH” No H, CI (*OCHa
, CHtOH. CQ, CN, COCFs, coct-ci alkyl,
CONl (w, CON HC+ alkyl of C1. C0N (alkyl of C, -03) t, COOC+
-Cs alkyl, C0OH, F, 1, NH,, N
HCl-C5 alkyl, N (Ct-C3 alkyl),. NHCHO,NHCOC1■,,NHCONH,. N HSO* CH*, N O! , OC+
Cs alkyl. OCOC113, OH, S CIC3 alkyl. SOC, -C3 nofuruki Jl/, 5ot(, -C3 nofurukik, SOI N I- [t, S Ot
N HC1C3 alkyl, SO! N(CI C3
alkyl)2, and 03tl A is one selected from the group consisting of N and C, ltl is a hydrogen atom, or R1 is a Cl to C4 saturated, unsaturated, acyclic, cyclic, mixed hydrocarbon, A modified hydrocarbon group, where the modified hydrocarbon group is one to two carbon atoms h<N, O, S, CQ, +3r. (1) is substituted with 1 to 2 atoms of the same or different heteroatoms selected from the group consisting of (2), and 1 to 3 hydrogen atoms are substituted with 1 to 3 fluorine atoms: R7 is C! From cps saturated, unsaturated, acyclic, cyclic,
A group of mixed hydrocarbons and modified hydrocarbons, where the modified hydrocarbon group is a group in which 1 to 4 carbon atoms are N, O, S, CQ, B.
r, is substituted by 1 to 4 identical or different heteroatoms selected from the group consisting of I, and 1 to 5 hydrogen atoms are substituted by 1 to 5 fluorine atoms; R, and R7 may not be fused; , R3 is one selected from the group consisting of H and ClC5 alkyl, R4 is one selected from the group consisting of H and CI (, provided that Xs+ Xs, Its, and R4 are hydrogen atoms When, and then x4 is CN or N Ot, R1 and n are CN or OCI (not 3, x4 is H,
CF,,Cll0. When CQ, CN, COCH3, F or NOl, R1 is NOt, SOCH
*or S OCtHs, R5 is No, 5or
t,SO,SO,NHR or 5OfN(R), where R is an alkyl, cycloalkyl, or allyl group of up to 10 carbon atoms which can be substituted with one or two atoms of sulfur or oxygen. 2. The sweetener according to claim 1, wherein said A is N. 3. The sweetener according to claim 1, characterized in that R4 is ■.・1. Said R5 Rikizuki! The sweetener according to claim 1, characterized in that the sweetener is selected from the group consisting of 5. Previous 3rd person 1. The sweetener according to claim 1, characterized in that the sweetener is selected from the group consisting of h (H and C11). 6. The sweetener according to claim 1, wherein x3 and
Q. Sweetener according to any one of claims 1 to 5, characterized in that it is selected from the group consisting of F. 7. The above X4 is H, CN, COOCtl 3, N
1↑ Flavoring agent selected from the group consisting of O2゜r. 8, r4iJ 3iL rt tka linear alk (e
n) Ct-C of (yn)yl, . C3-C13 of branched chain alk(en)yl, f;, yc
loalk(en)yl's Go C+3°Alk(e
n)yl cycloalk(en)yl C4Chf
f. Cycloalk(en)yl C, -C, of alk(en)yl. Alk(en)yl cycloalk(en)yl
alk(en)yl C−C+3゜Alk(en)yl
)yl bicycloalk(en)yl C7C1
Ct of 3゜condensation bicycloalk(en)yl
Cps. Alk(en)yl condensation bicycloalk(en)
C, -C, of yl. Condensation of bicycloalk(en)ylalk(en)
)yl Cs C13゜Alkenyl condensation bic
ycloalk(en)yl alk(en)ylc
e −C+3゜condensation bicycloalk(en)y
lalk(en)yl's C+o-C+31^1k(en
)yl condensation bicycloalk(en)ylalk
(en)yl C,, -C,,. Condensation of bicycloalk(en)ylalk(en)
)yl alk(en)yl CIl-C11Alk(
Lr1cycloalk(en)yl of en)yl condensation
Sweetener according to any one of claims 1 to 5, characterized in that it is selected from the group consisting of C1, J of alk(en)yl. 9, R2 is n C5t (+1. n CeI-Its, n
C7+1111°CH (CH30CHritc 1.
,+3. CII (Ci(*XCHz)*CH3
゜(CHy)sc +1 (CHz)t, (CI-1
Ri4CH (CH3)! . (CIIJsCI((Ctli)*, C5Hs, Ca
Cycloalkyl of Clo, CIlsC・lls, C
tl t c Cs1l ll+C11(C1la
) CsHs, Ctl(C1la) (!-CalIt
+. (CII,)*Cs1ls, (C11m)*c
Ca1l++. CII(CHt)CII*Ca1-1s, CI((
C+13) CHt-C-CaHll+C*I'L(CI
ls), Cm Cl. Cycloalkyl CIItC
slla(CHs), CHs c CaII13,
(Clls), ・C H (C 11 3
) C aH 4 (C tl i),
IC H (C H 2) C
C aH +o(C H s). (CIL)zCIr(C C30s)t, (CI(t
)scH(e CsHs)*, '4CH(CHa
) CHsCH (e CsHs). C H (C I (s) (C I-1 *)tc H
(e C !ll s)*. naphthyl, 5.6.7.8-tetrahydronaphthyl. Perhydronaphthyl, indenyl, indanyl. Naphthyl (C I4 2), 5.6.7.8-Tetrahydronaphthyl (CIls), Perhydronaphthyl (C
Hs), indenyl (CH.), indanyl (C +
-t S), fentyl, , C H t-naphthyl, C H t 5.6.7.8-tetrahydronaphthyl, cH*-perhydronaph j1 thyl, CIls-indenyl, CHt-indanyl. CH,-naphthyl (C H s), C I-1 t-
Perhydronaphthyl (Cl-13), CI-1 or indenyl (CH3). CH. -indanyl (CI(3), adamantyl, CH
, -adamandel, C I-1 (C H s) adamantyl. Selected from the group consisting of CH, -adamantyl (CHa);!
A sweetener according to claim 8, characterized in that: 0, said R is a modified hydrocarbon in which up to 4 carbon atoms are replaced by the same or different heteroaryl groups selected from the group consisting of S replacing C or C H t; N replacing CH or C H s. CH. N I (and 0) replacing C H s.'Br and ■. Claims 1 to 5, characterized in that up to 5 hydrogen atoms are replaced by fluorine atoms. A sweetener according to any one of the items described in 1. R. is N(CHs)CsHs. pyridinyl, piperidyl. 1t mopiperidyl. indolyl, indolinyl. isoindolinyl, quinolyl, isoquinolyl. pyrazinyl, pyrimidyl, intazolyl. quinoxalinyl. quinoazolinyl, purinyl,
O C II wc sH *. Pyranyl, benzofuranyl, methoxyphenyl, methyloxycarbonylphenyl. Methyloxycarbonylphenyl, 3,4-methylenedioxyphenyl, morpholinyl, benzoxazolyl, elanamide phenyl. Nitrile, nitro, thiophenyl, penzodiophenyl. 2.2.4.4-Tetramethylthiamicrobut-3-yl, thiozolyl, isothiacin) Lt. SO. C@Hi. S Ox Cal
-1++. S OtC7■, 3. The sweetener according to claim 10, characterized in that it is selected from the group consisting of chlorophenyl, fluorophenyl, and trifluoromethylphenyl. 12. A sweetener according to claim 1, which is represented by the following general formula. 13, FX Note X. and X, are H"i?, said X, is CN, said X, and The R1 is selected from the group consisting of H, CHs, and the R is CH(Clls)Csl-1s, CIItC
slls. C H(C H.3)-c- CII-I II, C
- Csl'l 11. e c? )(+1, e-CsHts, C Cs
l(+y. c C+oH+*, SOtCsHa, SO*C7■E
13. A sweetener according to claim 12, characterized in that the sweetener is selected from the group consisting of 11. 14.M agent is hydrochloride. Sodium, potassium. Sweetener according to claim 1, characterized in that it is selected from the group of physiologically acceptable salts consisting of ammonium, calcium and magnesium salts. 15. Food products characterized by adding the amount of the sweetener according to claim 1. Drinks, sugar confectionery, chewing gum, !13J combination medicines, veterinary preparations, toilets, Process for sweeteners, including cosmetic and hygiene products. 16. Preparations sweetened by the method of claim 15. 17. Effective amounts of sweeteners according to claim 1 and physiological A sweetener composition comprising a carrier found in Gum. Lactose, maltose, glucose, leucine, glycerol, mannitol, sorbitol, sodium bicarbonate, phosphoric acid, citric acid, tartaric acid, fumaric acid, benzoic acid, sorbic acid, propionic acid and its sodium, potassium, calcium salts and the above. A sweetener composition according to claim 17, characterized in that it is selected from the group consisting of all mixtures. 19. A sweetener composition according to claim 1, characterized in that it consists of a sweetener according to claim 1 and a different sweetener. 20. The different sweeteners include sucrose, corn syrup, fructose, aspartame (aspart II).
te), alttime, neohesperidin dividrochalcone, hydrogenated isomaltose. Stevioside, L-sugar, glycyrrhizine (glyc
yrrhizin), xylitol, acesulfame (acesu14am) K-, saccharin (sodium, potassium or calcium salt), cyclamic acid (cyc
Sweetener composition according to claim 19, characterized in that the sweetener composition is selected from the group consisting of sodium, potassium or calcium salts of lamicacid), trichlorogalactosucrose, monellin, thaumatin and mixtures thereof. December 7, 1988 1. Indication of the case 1988 Patent Application No. 88572 2. Title of the invention High potency sweetener 3. Patent applicant November 17, 1988 (shipment date) 6. Amendment Target 7: Correction details as per attached sheet (no change in content)

Claims (1)

[Scope of Claims] A sweetener represented by the following general formula, including its tautomeric forms and physiologically acceptable salts thereof. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ Here, X_3, X_4 and X_5 are the same or different and are selected from the group consisting of the groups shown below, H, Br, CF_3, CF_2CF_3, CH_2CF
_3, C_1-C_4 alkyl, CH=NOCH_3
, CH=NOH, CHO, CH_2OCH_3, CH_
2OH, Cl, CN, COCF_3, COC_1-C_
Alkyl of 3, CONH_2, CONHC_1-C_3
alkyl, CON (alkyl of C_1-C_3)_2
, COOC_1-C_3 alkyl, COOH, F, I
, NH_2, NHC_1-C_3 alkyl, N(C_
1-C_3 alkyl)2, NHCHO, NHCOCH
_3, NHCONH_2, NHSO_2CH_3, NO
_2, OC_1-C_3 alkyl, OCOCH_3,
OH, SC_1-C_3 alkyl, SOC_1-C_
alkyl of 3, alkyl of SO_2C_1-C_3, S
O_2NH_2, SO_2NHC_1-C_3 alkyl, SO_2N (C_1-C_3 alkyl)_2, and SO_3H; A is 1 selected from the group consisting of N and C
, R_1 is a hydrogen atom or R_1 is a C_1 to C_4 saturated, unsaturated, acyclic, cyclic, mixed hydrocarbon, or modified hydrocarbon group, where the modified hydrocarbon group is from carbon 1 to 2
atoms are replaced by 1 to 2 atoms of the same or different heteroatoms selected from the group consisting of N, O, S, Cl, Br, I, and 1 to 3 hydrogen atoms are replaced by 1 to 3 fluorine atoms. R_2 is a C_2 to C_1_3 saturated, unsaturated, acyclic, cyclic, mixed hydrocarbon, modified hydrocarbon group, where the modified hydrocarbon group is a group in which 1 to 4 carbon atoms are N, O ,S,
R_1 and R_2 are substituted by 1 to 4 identical or different heteroatoms selected from the group consisting of Cl, Br, I, and 1 to 5 hydrogen atoms are replaced by 1 to 5 fluorine atoms: R_1 and R_2 cannot be condensed. R_3 is one selected from the group consisting of H and C_1-C_3 alkyl, R_4 is one selected from the group consisting of H and CH_3, provided that X_3, X_5, R_3, and R_4 are hydrogen atoms , and then when X_4 is CN or NO_2, R_1 and R_2 are not CN or OCH_3, but X_
4 is H, CF_3, CHO, Cl, CN, COCH_3
, F or NO_2, R_1 is NO_2,
not SOCH_3 or SOC_2H_5, R_5 is not NO_2, SOR, SO_2R, SO_2NHR or SO_2N(R)_2, and R is 1 of sulfur or oxygen.
or an alkyl, cycloalkyl, or allyl group of up to 10 carbon atoms which can be substituted with two atoms. 2. The sweetener according to claim 1, wherein said A is N. 3. The sweetener according to claim 1, wherein R_4 is H. 4. The sweetener according to claim 1, wherein the R_3 is selected from the group consisting of H and CH_3. 5. The sweetener according to claim 1, wherein R_1 is selected from the group consisting of H and CH_3. 6. The above X_3 and X_5 are H, Br, CF_3, CH_
6. A sweetener according to any one of claims 1 to 5, characterized in that the sweetener is selected from the group consisting of 3, Cl, and F. 7. The above X_4 is H, CN, COOCH_3, F, NO
Sweetener according to any one of claims 1 to 5, characterized in that it is selected from the group consisting of _2. 8. R_2 is linear alk(en)(yn)yl C_2-C_1_
3. C_3-C_1_3 of branched chain alk(en)yl
, C_3-C_1_ of Cyclo alk(en)yl
3.Alk(en)ylcvcloalk(en)yl
C_4-C_1_3, Cyclo alk(en)y
l a1k(en)yl's C_4-C_1_3, Alk
(en)yl cycloalk(en)yl alk
(en)yl C_5-C_1_3 Alk(en)yl bicyclo alk(en)
C_7-C_1_3 of yl, bicyclo a of condensation
C_7-C_1_3 of lk(en)yl, Alk(en)yl
)yl condensation bicycloalk(en)yl C_8
-C_1_3, condensed bicyclo alk (en)
C_8-C_1_3 of yl alk(en)yl, bicycloalk(en) of Alk en yl condensation
)yl alk(en)ylC_9-C_1_3, condensation tricycloalk(en)ylC_1_0-
C_1_3, tricycle of Alk(en)yl condensation
o alk(en)yl C_1_1-C_1_3, condensation tricyclo alk(en)yl alk
C_1_1-C_1_3 of (en)yl, tricyclo alk of Alk(en)yl condensation (
Sweetener according to any one of claims 1 to 5, characterized in that it is selected from the group consisting of C_1_3 of en)ylalk(en)yl. 9. The above R_2 is n-C_5H_1_1, n-C_6H_1_3, n-C
_7H_1_5CH (CH_3) (CH_2)_2CH
_3, CH (CH_3) (CH_2)_3CH_3, (
CH_2)_3CH(CH_3)_2, (CH_2)_4CH(CH_3)_2, (CH_2)_5CH(CH_3)_2, C_6H_5
, C_6-C_1_0 cycloalkyl, CH_2C_
6H_5 CH_2-c-C_6H_1_1, CH(CH_3)C
_6H_5CH(CH_3)-c-C_6H_1_1,
(CH_2)_2C_6H_5 (CH_2)_2-c-
C_6H_1_0, CH(CH_3) CH_2C_6H
_5CH (CH_3) CH_2-c-C_6H_1_1
, C_6H_4 (CH_3), cycloalkyl of C_6-C_1_0 (CH_3), CH_2C_6H_4 (C
H_3), CH_2-c-C_6H_1_0(CH_3
), CH (CH_3) C_6H_4 (CH_3), CH
(CH_3)-c-C_6H_1_0(CH_3), (
CH_2)_2CH(c-C_3H_5)_2, (CH
_2)_3CH(c-C_3H_5)_2, CH(CH
_3) CH_2CH(C_3H_5)_2, CH(CH
_3)(CH_2)_2CH(c-C_3H_5)_2
, naphthyl, 5,6,7,8-tetrahydronaphthyl,
Perhydronaphthyl, indenyl, indanyl, naphthyl (CH_3), 5,6,7,8-tetrahydronaphthyl (CH_3), perhydronaphthyl (CH_3
), indenyl (CH_3), indanyl (CH_3)
, fentyl, CH_2-naphthyl, CH_2-5,6
, 7,8-tetrahydronaphthyl, CH_2-perhydronaphthyl, CH_2-indenyl, CH_2-indanyl, CH_2-naphthyl (CH_3), CH_2-tetrahydronaphthyl (CH_3), CH_2-perhydronaphthyl (CH_3), CH_2-indenyl ( CH
_3), CH_2-indanyl (CH_3), adamantyl, C
The sweetener according to claim 8, characterized in that it is selected from the group consisting of H_2-adamantyl, CH(CH_3) adamantyl, and CH_2-adamantyl (CH_3). 10. R_2 is a modified hydrocarbon in which up to 4 carbon atoms are replaced by the same or different heteroatoms selected from the group consisting of: S replacing C or CH_2; S replacing CH or CH_3; N, NH and O replacing CH_2, Cl, Br and I replacing CH_3, wherein up to 5 atoms of hydrogen are replaced by fluorine atoms, Claims 1 to 5 A sweetener according to any one of the items listed in Section 1. 11, R_2 is N(CH_3)C_6H_5, pyridinyl, piperidyl, homopiperidyl, indolyl, indolinyl, isoindolinyl, quinolyl, isoquinolyl, pyrazinyl, pyrimidyl, intazolyl, quinoxalinyl, quinoazolinyl, purinyl, OCH_2C_
6H_5, pyranyl, benzofuranyl, methoxyphenyl, methyloxycarbonylphenyl, 3,4-methylenedioxyphenyl, morpholinyl, benzoxazolyl, ethanamidophenyl, nitrile, nitro, thiophenyl, benzothiophenyl, 2,2,4,4 -Tetramethylthiamicrobut-3-yl, thiazolyl, isothiazolyl. SO_2C_6H_5, SO_C_6H_1_1, SO
The sweetener according to claim 10, characterized in that it is selected from the group consisting of _2C_7, H_1_3, chlorophenyl, fluorophenyl, and trifluoromethylphenyl. 12. A sweetener according to claim 1, characterized in that it is represented by the following general formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ 13. The above X_3 and X_5 are H, and the above X_4 is C
N, said X_3 and X_5 are selected from the group consisting of Cl, CF_3, CH_3, and F, said X_4 is selected from the group consisting of H and CN, and said R_1 is selected from the group consisting of H and CH_3. and the R_2 is CH(CH_3)C_6H_5, CH_2
C_6H_5CH(CH_3)-c-C_6H_1_1
, c-C_6H_1_1, c-C_7H_1_3, c-
C_8H_1_5, c-C_9H_1_7, c-C_1
_0H_1_9, SO_2C_6H_5, SO_2C_
13. The sweetener according to claim 12, characterized in that it is selected from the group consisting of 7H_1_3. 14. Sweetener according to claim 1, characterized in that said agent is selected from the group of physiologically acceptable salts consisting of hydrochloride, sodium, potassium, ammonium, calcium, magnesium salts. 15. Food products, drinks, sugar confectionery, chewing gum, pharmaceutical preparations, veterinary preparations, toilets, cosmetics and hygiene, characterized by adding an effective amount of the sweetener according to claim 1. Method for sweetener containing products. 16. A preparation sweetened by the method of claim 15. 17. A sweetener composition comprising an effective amount of a sweetener according to claim 1 and a physiologically acceptable carrier. 18. The carrier is polydextrose, starch, maltotegistrin, cellulose, methylcellulose, carbomethylcellulose, hydromethylcellulose, microcrystalline cellulose, sodium alginate, pectin, gum, lactose, maltose, glucose, leucine, glycerol, mannitol, sorbitol,
Claims characterized in that it is selected from the group consisting of sodium bicarbonate, phosphoric acid, citric acid, tartaric acid, fumaric acid, benzoic acid, sorbic acid, propionic acid and its sodium, potassium, calcium salts and mixtures of all of the above. A sweetener composition according to item 17. 19. A sweetener composition comprising the sweetener according to claim 1 and a different sweetener. 20. The different sweeteners may be sucrose, corn syrup, fructose, aspartame.
), alitame, neohesperidin dihydrochalcone, hydrogenated isomaltose, stevioside, L-sugar, glycyrrhidine
zin), xylitol, acesulfarm (aces
ulfam)-K, saccharin (sodium, potassium or calcium salt), cyclamiic acid (cyclami
sodium, potassium or calcium salts of cacid), trichlorogalactosucrose. monellin, thaumatin,
Sweetener composition according to claim 19, characterized in that it is selected from the group consisting of mixtures thereof.