TW387897B - N-(3,3-dimethylbutyl)-l-aspartyl-d-<alpha>-aminoalkanoic acid n-(s)-1-phenyl-alkanamide useful as a sweetening agent - Google Patents

Description

A A7 — B7 Five 'invention description (1) The present invention relates to a novel compound derived from a dipeptide that can be used as a # flavoring agent. These products are particularly useful for sweetening a variety of products, especially beverages, foods, desserts, flours, chewing gum, hygiene products, cosmetics and cosmetic, pharmaceutical and veterinary products. It is known that in order for the sweetener to be used on an industrial scale, the sweetener must first have a strong sweetness effect in order to reduce the use cost as much as possible. Second, it must have satisfactory stability, i. E. Combined use The stability of conditions. Among the sweeteners currently on the market, a dipeptide derivative known as aspartame, L-aspartyl-L-phenylalanine methyl ester, has the following chemical formula: COOCH3 j C〇-NH ► Η ， Η! F (please read the note on the back before filling in this page) 装. &Gt; ΤΓ

It is printed by the Consumers Cooperative of the Central Government Bureau of the Ministry of Economic Affairs, which is the most widely used user (US. 3,475,403). The compound has a rather weak sweetness potency of about 120 to 180 times the sweetness of the same weight sucrose. Even though its organoleptic properties are excellent, the main disadvantage of this compound is that it is an expensive product because of its relatively low sweetness intensity, and its stability is quite low under the condition of generally using sweeteners, so it is very difficult to use. Limits its application in the industrial park. -4-This paper uses China National Standards (CNS &gt; A4 size (210X297 mm). A7 B printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs.) 5. Description of the invention (2) ^: FR 92 13615 In the document, the patent applicant proposes a sweetener having the following formula: C0—NH — R.! · R—NH ► C Η * j (CH2) n coon where: R is a saturation with four to thirteen carbon atoms Or unsaturated, acyclic, cyclic or mixed hydrocarbon groups; η is equal to 1 or 2; and R 'is represented by the following chemical formula: Υ

I

I ·-C— Η

I

I t Z · wherein: Y is selected from the group consisting of the following atoms: COOCH3, COOC2H5, CH3, CH2OH, CON (CH3) 2, C6H5, 2-furanyl, and Η; Z is selected from the group consisting of: CH2C6H5, C6H5 , N-C4H9, COOCH3, COOC2H5, COOC3H7, COO hydrazone and CONHR, ', where R "is selected from the following atomic circles: CH3, CH2CH3, •. Taste _______-_ 5-_; _ This paper size is applicable to Chinese countries Standard (CNS) A4 (210X297mm) ----- ~: I "install-(please read the notes on the back before filling in this I) Order A7 B7 V. Description of the invention (3) ch2ch2ch3, ch2ch2ch (ch3) 2, CH (CH3) COOCH3, CH (c-C3H5) 2, CH (c-C3H5) C (CH3) 3, fluorenyl, 2,6-dimethylcyclohexyl, 2,2,5 , 5-tetramethyl, cyclopentyl, and 2,2,4,4-tetramethyl-3_thietanyl 0 .. A fulfilled form described in FR 92 13615, containing L-asparagine of the following chemical formula Acid derivatives (η = ι):

R

NH

H a ^ 2 〇 o ^ Η o c! Lc! Lc I

T1 tf N

H -on VI · 1 —r0 —I— CIO-s Η Κ -LI. --------. I 「装 —— (Please read the precautions on the back before filling this page) 1T- Ministry of Economic Affairs The Central Consumers Bureau employee consumer cooperatives have printed the definitions of “R, Y and R” as described above. A more suitable compound in the form in which the present invention is performed is N- (3,3 Γ dimethylbutyl) -L · asparagine Ν-N- (dicyclopropylmethanolyl) -〇-propylamine amine, Its chemical formula is as follows:

Y

ch3 I

I? 〇 — NH ► C H CH 广 卜 广 CH 「1〇_nh_r„ CH3 0H2

I

COOH where γ represents a methyl atom 圏 and R, represents a dicyclopropylmethanolyl atomic circle,

A7 B7 5. Description of the invention (4) The sweetness potency of this compound is 2,500 times the sweetness potency of equal weight sucrose in a 2% sucrose solution. The basis of the present invention is based on the finding that it is possible to obtain previously exemplified novel compounds with appropriately selected Y and R substituents, which are different from those proposed in the previous documents. Therefore, when γ represents ethyl, isopropyl or (R) -α-hydroxyethyl radical and R "represents a (s) · α-ethylbenzyl, (S) -i-methylbenzyl Or (annoying)-^ _ methoxymethylbenzyl radicals, 'new compounds with excellent sensory qualities with extremely high sweetness potency of up to 8,000 times the sweetness potency of sucrose of equal weight can be obtained. The stability in neutral solution is significantly higher than that of aspartame, which should make it more widely used in food preparation than aspartame. Therefore, the system of the present invention provides a formula corresponding to the following New type of sweetener: ------: I 「装-(Please read the precautions on the back before filling in this page}, ΤΓ. 3 H c 2 Η c53-H3 cIcIc cb 2 • ί la c

NH Η Η f-2 ο, Η ο —CIC He Η Ν YI »c — Η j CO —NH —R” Printed by Zhengong Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs where: Y is C2H5 or ch (ch3) 2 Or (r) ch (oh) ch3; and R, 'is (S) CH (C2H5) C6H5, (S) CH (CH3) C6H5 or (R) CH (CH2OCH3) C6H5, which is particularly advantageous for carrying out the present invention. 'The compound form is N-(3,3 _ two paper sizes are applicable to Chinese national standards (CNS &gt; A4 specifications (210X297 mm) A7 V. Description of the invention (5) Methylbutyl) -L-Asparagus Aminodonyl-D_a_aminobutyric acid ... ⑻ ^ phenyl_propanamide, its chemical formula is as follows: t CH, CH3-C-CH2-CH:

NH CH,

I? 〇—NH ·-C, H!; Bu H fh C〇〇H

C〇 —NH

C- · HI has a sweetness effect of about 0 times that of an equal weight cheap sugar in a 2% cheap sugar solution; it is N (3'3-methylbutyl) _L • asparagine base_D brilliant amino acid N_ (s) _ 1-phenyl-propanamide, its chemical formula is as follows: -------- ^ 装 ---- ^-1Τ- (Please read the precautions on the back before filling this page) ch3 I CH3 — C — CH2 — CH2 — NH CH,

CO-NH

I

c H

I ch2 C〇〇h 9H (CH3) 2 I ▲

C-H {CO — nh

11 5 1 5 H f Η 6- &quot; 2 HI printed by the Central Laboratories of the Ministry of Economic Affairs, Shellfish Consumer Cooperative, which has a sweetness effect of about 3,000 times that of equal weight sucrose in a 2% sucrose solution; Ν -(3,3 · dimethylbutyl) _L_asparagine acyl group_D_a_aminobutyric acid ν · (S) -l-phenyl · 2 · methoxy-1-ethylamidine, which The chemical formula is as follows: • 8-ΐ Paper size is applicable to Chinese National Standard (CNS) A4 (2ίΟ × 297 mm) &quot; Α7 Β7 5. Description of the invention (6) CH:

CHj —C — CH2 — CH2 — NH CH,

C〇-— NH I H I ch2I COOH

2H5 I c〇nh C〇H5 C- · HI CH2OCH3 has a sweetness effect of about 4,000 times that of the same heavy sugar in a 2% Tibetan sugar solution; it is heart (3'3-dimethyl &amp; butyl ) _L · aspartamidinyl | valine acid n_ (s) _ 1-phenyl-2 · methoxy-1-acetamidamine, its chemical formula is as follows. Ch3 CO—ΝΗι

CH3— C — CH2 — CH2 — NH ► C H

fH (CH3) 2 卜 H 1 CO — NH ------ i-pack — (Please read the note on the back before filling this page) tr * CH,

CH2I COOH c6h5 g_h I ch2och3 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. It has a sweetness effect that is about 4,000 times that of equal weight sucrose in a 2% sucrose solution. In addition, it has been confirmed that the stability of these compounds peculiar to the present invention is significantly higher than that of Aspartame under the conditions generally used for food preparation. This advantage is especially important because the limitation in the use of aspartame in certain food preparations comes from its low stability in a nearly neutral medium. At pH of about 7, this pH is often used in some products. Low stability encountered in foods such as dairy / flour-like foods or in preparations requiring high-temperature cooking. -9- The X degree of this paper is applicable to China National Standards (CNS) A4 (210x297 mm). The Central Government Bureau of the Ministry of Economic Affairs, Shellfish Consumption Cooperation Du printed A7 B7 V. Description of the invention (7) The compounds have better stability in acidic media with a pH of about 3, which is equivalent to p Η 値 of soft drinks, and soft drinks constitute one of the main applications of sweeteners. Therefore, the aging was promoted by prolonging the time of heating the aqueous solution of ρΗ3 at 70 ° C. The results of the investigation showed that the specific compound of the present invention, N- (3,3-dimethylbutyl) -L-asparagine The group D-α-aminobutyric acid N- (S) -1-phenyl-1-propanamide has a half-life of about 72 hours. By comparison, under the same conditions, the half-life of aspartame is only about 24 hours, which is equivalent to: the stability of the compound according to the present invention is about three times greater than that of aspartame. At pH 7, the results of the same aging promotion show that the same compound, N- (3,3-methylbutyl) -L-asparagine D-α-aminobutyric acid N- (S ) -1 · Phenyl-1-propanamine has a half-life of about 12 days, and under the same conditions, the half-life of aspartame is only about 10 minutes, which is quite ... the stability of the compound according to the present invention is greater than about Aspartame 1,700 times. When applied to foods, it is known from its high sweetness effect that the compound of the present invention has an advantage over aspartame in that it can be used in an extremely low amount of an effective sweetener. Therefore, it is possible, for example, to dissolve about 20 mg of N- (3,3-dimethylbutyl) -L · asparagine D-α-aminobutyric acid in a liter of soft drink] ^ -(8) -1-Phenyl-1-propanamine is used to replace 550.11 aspartame, and thus can reduce the sweetener consumption by about 27 times, while still maintaining the same sensory quality. The sweetener of the present invention can be added to any edible product that wants to give it a sweet taste, as long as it is added in a sufficient proportion to achieve the desired sweetness. The optimum concentration of the sweetener will depend on various factors, such as, for example, the sweetener's ____-10- This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Please read first Please fill in this page on the back of the note.) Binding A7 printed by the Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economics. 5. Description of the invention (8) Sweetness potency, storage conditions and conditions of use of the product, special ingredients and Wanted sweetness. Any qualified person can easily determine the optimum ratio of sweeteners necessary to obtain an edible product through routine sensory analysis'. Generally, the sweetener of the present invention is added to the edible food in proportion to the sweetness potency of the compound, which ranges from 5 mg to 50 * mg of the sweetener per kg or liter of the edible product. Concentrated products will obviously contain higher amounts of sweeteners and will subsequently be diluted according to the end use purpose. The sweetener of the present invention may be added to a product to be sweetened in a purified form, but it is usually mixed with an appropriate food additive or accumulation agent because of its high sweetness potency. Conveniently, suitable carriers or builders are selected from the group consisting of polydextrose, starch, maltodextrin, cellulose, methylated cellulose, hydrocarbon methylated cellulose and other derivatives of cellulose, Sodium alginate, pectin, gum, lactose, maltose, glucose, lectin, glycerin, mannitol, sorbitol, sodium bicarbonate, acid, citric acid, tartaric acid, fumaric acid, benzoic acid, sorbic acid Acids, and propionic acid and its sodium, potassium and calcium salts, and equivalents. 'In edible products, the sweeteners of the present invention can be applied as the sole sweetener or in combination with other sweeteners, such as sucrose, corn syrup, fructose' sweet double analogs, or derivatives ( Aspartame, alitame), neohesperidin dihydrochatra, hydrogenated isomalt_sugar, stevia, L sugar (L sugar0, glycyrrhizin, xylitol, sorbitol, mannose Sugar alcohol, acesulfaml-K, saccharin and its sodium salt, potassium, ammonium ___- 11 * This paper size applies to China National Standard (CNS) A4 specification (210X297 public -------) (Please read the precautions on the back before filling out this page.) Pack. IT · Consumer cooperation with employees of the Central Standards Bureau of the Ministry of Economic Affairs, printed A7 _ ^ _ B7 '_ V. Description of the invention (9) and calcium salts, dicyclohexyl sulfonate And its sodium, potassium and calcium salts, sucralose, monellin, somatame, and their equivalents. The compounds of the present invention are prepared via a reductive N-alkylation which condenses a dipeptide of the following chemical formula Precursor:

Y

I! · CO —NH C Η ί i h2n-c-h CO-NH-R &quot;

ch2 I COOH. where Y and R "are as defined above, and contain 3,3-dimethylbutylaldehyde in the presence of the reducing agent. The reducing agent may be based on the procedure described in the certificate of WO 95/30689, and the relative pressure is 1 to 3 bar hydrogen containing a platinum or palladium-based catalyst or sodium cyanoborohydride according to the procedure described in the FR 92 13615 certificate. 'The above dipeptides can be easily obtained by implementing the basic principles of peptide synthesis Precursor Chemistry: Protection of Amine and Carboxyl Groups of Amino Acid Precursors, Deprotection, and Traditional Activation and Peptide Coupling Methods. These techniques are detailed in many politicians, most of which are cited It is "Practical peptide synthesis" by M. Bodanszky and A. Bodanszky, Springer-Verlag, Hong Yue, 1984.284 pp. Purification of the compounds of the present invention is performed according to standard techniques, such as recrystallization and chromatographic analysis. It The structure and purity have been tested by green transmission technology (thin layer color analysis, high performance liquid color, layer analysis, infrared spectroscopy, nuclear magnetic resonance, elemental analysis) 卩 _; _ ^ _ -12 -__ This paper size is applicable China National Standards (CNS) A4 Specifications 210X297 males) ----: --- 1 .--:-^ equipment ---- U--1T ------- (Please read the precautions on the back before filling in this page) A7 B7 V. Description of the invention (10) The sweetness potency of the compounds described in the examples has been evaluated by eight experienced personnel. In the evaluation, various concentrations of the compound aqueous solution and 2%, 5% or 10% control group sucrose aqueous solution were used. Taste comparison. After comparing the sweetness potency of the test compound &gt; with sucrose, the control shows that the sweetness intensity is equal, ie when most of the panelists think that the test compound solution and the control group sucrose solution have the same sweetness intensity The weight ratio of the compound to sucrose. The stability of the compound of the present invention and aspartame was measured by high performance liquid chromatography (HPLC) in an acidic medium (phosphate buffer solution at pH 3) or in (A phosphate buffer solution at pH 7 and the amount of product remaining under the effect of accelerated aging at a temperature of 70 ° C. In this way, the stability of the test compound is evaluated by the half-life (corresponding to 50% decomposition time and time). The way in which the invention is implemented and the benefits derived from it can be more easily attributed to This is shown in the working examples. The examples are prepared by the following formula: N- (3,3 · dimethylbutyl) _L-aspartylamino Da-aminobutyric acid N- (S) -1-phenyl-1 -Propanamide: (Please read the notes on the back before filling out this page) -a Γ-

V Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Common Carriage, CHj I CH3-T- c — CH2 — CH; CH,

C2H5 1 CO—!! ΝΗ ► C, I I ch2 COOH

CO —NH C〇H5 C — H 1 c2h5 15 g (0.145 mol) of D-a-aminobutyric acid (Aldrich Product No. 11,612 · 2) and 5.82 g (0.145 mol) of sodium hydroxide 13 in 150 cm3 water This paper size is applicable to China National Standard for Ladder (CNS) A4 (210X297 mm). Printed by the Zhengong Consumer Cooperative of the Central Standards Bureau of the Ministry of Economy. At the same time, 24 38 g (0 145 mol) of benzyl aquamate and 5.82 g (0.145 mol) of an aqueous solution of sodium hydroxide (4N) were added dropwise to the solution. It was then kept stirring at 0 ° C for 3 hours. The reaction mixture was washed with diethyl ether (3 × 30 cm3) and then acidified with hydrogen acid (6N) until ρ η was about 1. The white precipitate formed by the reaction was separated by filtration, washed with water and dried. 26 g of N-benzyloxycarbonyl-D-π-aminobutyric acid having a melting point of 80 ° C was finally obtained (yield 75%). In this way, 3 g (13 mmol) of the compound was prepared as a solution in 50 cm3 of tetrahydrofuran, and then cooled to -15 ° C, then 1.28 g (13 mmol) of N-methylmorpholine and 1.15 g (13 Millimolar) isobutyl aquamate. After stirring at this temperature for 2 minutes, then 1.71 g (13 mmol) of (S) -1-phenyl-1-propylamine (previously prepared according to the document J. Chem. Soc. 1940, p. 336-8) was added. The mixture was slowly warmed, and then stirred at room temperature for 2 hours. After removing the N-methyl group? #Hydrogen acid precipitate by filtration, the solution was washed with 20 cm3 of tetrahydrofuran. The mash was concentrated to dryness and the resulting residue was placed in 150 cm3 of diethyl ether. The resulting solution was washed successively with a 0.1N hydrogen acid solution, a 5% sodium carbonate solution, and then with water (3 × 30 cm3 was used for each wash). After the essence solution was dried over anhydrous sodium sulfate, the solution was concentrated to dryness in the air, which resulted in 3.8 g of melting point 129eC2N-phenyloxycarbonylaminobutyric acid N- (S) -1-phenyl-1-propanamine White solid residue (82% yield). Its purity is checked by thin layer chromatography on a silicone G6 0 (silicon dioxide support is Merck No. 105554), eluted with aerosol-acetone (9-1), and concentrated by potassium dichromate. The sulfuric acid mixture developed color, Rf = 0.45. Contains 10 at 3 50 mg. / ❶ Palladium Activated Carbon (Fluka Product No. 75990) • 14_ This paper size applies to China National Standard (CNS) A4 (210X297 mm) ——J-II 丨 一 —— (Please read the precautions on the back first (Fill in this page)-Order printed by the Consumers Cooperative of the Central Government Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (12) In the presence of 100 cm3 contains 3.6 g (10 millimolar-benzyloxycarbonyl · D-α -Aminobutyric acid N- (S) -1_-phenyl · ι · propylammonium alcohol solution was put into hydrogen at atmospheric pressure for 18 hours. After removing the catalyst by filtration-method, the solution was concentrated to empty Dry. An oily residue, D-α-aminobutyric acid N · (S) -1-phenyl-1, propylamine, is obtained. Its purity is determined by the silica gel G60 (silica dioxide is Merck No. 1.05554) Thin layer colorimetric analysis to test 'dissolve with butanol · acetic acid-water (8-2-2) and develop color with Ninhydrin reagent, Rf = 0.57. 50 cm3 contains 3.58 g (10 mmol) N-benzyloxycarbonyl-L·L-aspartate tetrabenzylfuran solution was cooled to -15. After that, 1 g (10 mmol) was added successively. N. fluorenylmorpholine and 1.37 g (1 0 mmol) isobutyl aquamate. After 2 minutes of incubation at this temperature, the previously prepared D-α · aminobutyric acid N- (S) -1-phenyl-1-propanamine was added The mixture was slowly heated and then stirred at room temperature for 2 hours. After the N-methylmorpholine hydrochloride precipitate was removed by filtration, it was washed with 20 cm3 of tetrahydrofuran. The filtrate was concentrated to dryness and the residue was dried at 50 cm3. It was mashed in ethyl ether. The white solid was separated by filtration and washed again with 20 cm3 of diethyl ether. In this way, N-benzyloxycarbonyl with a melting point of 130 ° C was obtained;? Ester-L-aspartyl-D-α-aminobutyric acid N- (S) -1-phenyl-1-propanamide 5 g (yield 89%). Its purity is measured in silicone G60 (two The silicon oxide support was tested by Merck No. 1.05554) thin-layer chromatographic analysis, and was eluted with aerated acetone (18_2), and developed with a chromium sulfate mixture, Rf = 0.64. 500 mg containing 1 〇% Palladium Activated Carbon (Fluka Product No. 75990), 100 cm3 contains 5g (8.9 millimolar) of N-benzyloxycarbonyl -15- This paper is compatible with Chinese National Standard (CNS) A4 specifications ( 210X297 mm) ----; ------- (Please read the notes on the back before filling out this page)

Printed by A7 B7, Shellfish Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs 5. Description of the invention (13) Benzyl ester-L-aspartyl-De-amino-butyric acid N- (S) -1-phenyl- A methanol solution of 1-propanamide was poured into hydrogen at atmospheric pressure for 18 hours. The catalyst was removed by filtration, and the solution was concentrated to dryness. Thus, a white solid L · aspartamido-0- &lt; ^-aminobutyric acid ^ (8) -1-phenyl-1-propanamine 2.4 g was obtained. (80% yield). Its purity is verified by thin layer chromatography on a silicone G60 (Silica dioxide support is Merck No. 1.05554), and dissolved in butanol-acetic acid-water (8-2 · 2). Color development, Rf = 0-5. Its melting point in this amorphous state is 195 ° C. In a reactor equipped with a stirrer to ensure that the hydrogen can move well into the liquid phase, while stirring, add 15 cm3 of a 0.1 M aqueous acetic acid solution, 26 mg of activated carbon with palladium ( Fluka Product No. 75990), 58 mg (0.57 mmol) of 3,3-dimethylbutylaldehyde (Eight 1 (1 | ^ 11 such as · 35,990_4), 15 cm3 of methanol and 130 mg (0.38 mmol) (Ear) N- (S) -1-phenyl-1-propanamide, L-aspartylaminoaminobutyric acid, previously prepared. After the reactor was purged with a stream of nitrogen, the relative pressure was -2 bar. (01 · 0.2 MPa), the mixture was hydrogenated at room temperature for 18 hours, and then added again with 19 mg (0.19 mmol) of 3,3-dimethylbutylaldehyde for 8 hours. The progress of the reaction The monitoring was based on a thin layer of silica gel 60 254 (Merck No. 105554) on aluminum flakes, and analyzed by butanol-acetic acid water (8: 2: 2). The color was developed, and Rf = 0.67. Finally, the reactor was purged with a stream of nitrogen to interrupt the reaction, and the catalyst was separated by filtration with a precision filter paper (0.5 # m). Then the concentrated solution was concentrated by air evaporation and the concentration was about 50 cm3 diethyl ether washed white solid. Finally, a high purity of 167 ° C melting point (purity greater than -16 as determined by HPLC-this paper size applies to China National Standard (CNS) A4 specification (210X297 mm> m ^ n _ I-H an -I- fi (Please read the notes on the back before filling in this page) tr Printed by the Central Samples Bureau of the Ministry of Economic Affairs Shellfish Consumer Cooperative A7 B7 V. Invention Description (14) 9 8%) Ν · (3,3 · dimethylbutyl) -L_aspartylamino_Da · aminobutyric acid N- (S) -1-phenyl-propionamine white powder 150 mg (yield 92 %). Molecular formula: C23H37N304 NMR (200 MHz, 1H, ppm), DMSO D6: 0.80 (s, 15H), 1.33 (t, 2H), 1.67 (m, 4H), 2.4 (m, 4H), 3.54 (m , 1H), 4.30 (q, 1H), 4.70 (q, 1H), 7.22 (m, 1H), 7.28 (s, 5H), 8.35 (t, 2H). "Lichrospher 100 RP-18 end cap" Type, 244 mm long, 4.6 mm diameter Merck column, eluent: 65 mM ammonia acetate buffer-acetonitrile (70: 30) 'flow rate: 1 ml / min, detector: refractometer, its retention time For 16.1 minutes. The sweetness potency of this compound is approximately equivalent to 8,000 times that of an equal weight sucrose in a 2% sucrose solution, 6,000 times in a 5% sucrose solution, and 5,000 times that in a 10% sucrose solution. Compared with aspartame, the 20 mg / L aqueous solution of this compound is equivalent to the sweetness potency of aspartame 550 mg / L aqueous solution, and its relative sweetness potency is about 27 times higher than that of aspartame. Figure 1 shows aspartame and N- (3,3-diamidobutyl) -L-asparagine in an acidic medium (continuous acid buffer) heated at pH 7 (TC at pH 3). -D-α-aminobutyric acid N- (S) -1-phenyl-1-propanylamine solution aspartame (curve 1) and N- (3, 3-Dimethylbutylaspartame-D- or -aminobutyric acid N- (S) -1-phenyl-1-propanamine (curve 2) Comparison chart of stability curves. Under these conditions In the following, the half-life of aspartame is 24 hours, while the compound of the present invention is about 72 hours, which is equivalent to: the stability of the compound of the present invention is 3 times better than that of aspartame. ___ · 17-This paper size applies China National Standard (CNS) A4 (210X297mm) '' '-(Please read the notes on the back before filling this page)-Equipment · A7 B7 V. Description of the invention (15) Aspartame and N- (3,3-dimethylbutyl) _L-asparagine_D_ &gt; heated at 70 ° C in a pH 7 neutral medium N-ί S ) -1-Phenyl-1 _-Aspartame measured during pro-aging solution (curve 1) and N- (3,3-dimethylformate) of the present invention Butyl) · L_aspartamido_D_ α-aminobutyric acid N- (S) -1-phenyl-1-propanamide (curve 2) Comparison chart of stability curves. Under these conditions, The stability of aspartame is very small (half-life 10 minutes), and the compound of the present invention has a half-life of about 12 days, which is equivalent to the stability of the compound of the present invention which is about 1700 times higher than that of aspartame. 'Now according to the present invention, the sweetness potency of other compounds obtained by those skilled in the art according to experimental methods similar to the above is shown in Table 1. • Table 1 1-· 3' i ^ n--i_ 1 ^ 1 ^^ 1, am i (please read the notes on the back before filling this page) CH, Y CH3 CO 一 NH _ 1 «| -11CH2 — CH2 NH _ 1 C— Η 1 ίο ch3 1 CH, i COOH 、-, ^-Printed YR by the Consumers' Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs "Sweetness Efficacy * C2H5 (S) CH (C2H5) C6H5 8,000 (CH,) 2CH (S) CH (C2H5) C6H5 3,000 C2Hs (S) CH (CH3) C6H5 2,000 C2 H5 (r) ch (ch2och3) c6h5 4,000 (CH3) 2CH (R) CH (CH2OCH3) C6H5 4,000 Sweetness efficacy compared to 2% sucrose solution of the same weight -18- This paper size is applicable to Chinese national standards (CNS ) A4 specification (210 × 297 mm) A7 _ B7_ V. Description of the invention (15a) Brief description of the drawing Figure 1 shows the stability compared (p Η 3, 70 ° C). Figure 2 shows the comparative stability (pH 7, 70 ° C). (Please read the precautions on the back before filling this page) -ο · nnn I nnnnn ii I Line-Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs-18a- This paper size applies to Chinese national standards (CNS &gt; A4 specifications (210 X 297 mm>

Claims (1)

387897 A8 B8 C8 D8 6. Application for patent application, 1 ~ — 1. A compound of the following formula: ch3 — C — ch2 — ch2 — NH I ch3 c —I cl — cuoo NH H ic-! Co Η NH R, where: Y Is C2H5, ch (ch3) 2 or (r) ch (oh) ch3; and 'R,' is (S) CH (C2H5) C6H5, (s) ch (ch3) c6h5 or (r) ch (ch2och3) c6h5. 2. The compound according to item 1 of the scope of application for a patent, characterized in that the compound is N- (3,3-dimethylbutyl) -L-aspartylamino_D-α-aminobutyric acid N- (S) -1_phenyl-1-propanamine ··: CH: CO—NH CH3 ~? — CH2 — CH2 — NH CH? 2H5. (:, H CO —NH '---- 1: IIλέI- (Please read the precautions on the reverse side before filling out this page), 1T. CH, COOH feHs j C- · H! C2H5 printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs; The compound of the present invention is characterized in that the compound is N- (3,3-dimethylbutyl) -L-aspartylamino-D · valine N- (S) -1-phenyl -1-Propanamide: -19- This paper has been applied from China (CNS) (21GX297 mm) 387897 A8 B8 C8 D8 6. Application scope of patent ch3, CH (CH3) 2 I CO—NH— C — H CH3 — C — CH2 — CH2 — NH ► CH CO —NH CH CH, 〒H2 CQOH C7H '4. The compound according to item 1 of the patent application park, characterized in that the compound is N- (3, 3 · dimethyl-butylbutyl) -L-aspartyl-D-α-, aminobutyric acid N- (S) -1- Methyl-2-methoxy-1-acetamidamine: / c2h5 CH, 〒h3 CO—NH ·-(: —h c6h C — CH2 — CH2 —NH c ^ H CO —NH ·-H ---- I;-. I 「装-(Please read the notes on the back before filling this page) CH, CHi I-COOH CH2〇CH; 5. The compound according to item 1 of the scope of patent application. The compound is N- (3,3-dimethylbutyl) -L-aspartyl-fluorenyl-D-valine N- (S) -1-phenyl-2-methoxy-ethyl Phenylamine: printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs CH (CH3)-* j 13 CO—NH »-C ^ Η CH] C — CH2 * — CH2 · — NH C ^ H CHj ch2 • COOH CH: CfiH. CO — NH ► CH CH2OQHs -20-This paper size applies to China National Standard (CNS) A4 (2IOX297 mm) 6. Two kinds of compounds according to any one of items 1. to 5 of the patent application, for use as sweeteners. Item 7. ^ Prepared according to any one of the items in item ⑴ of the patented patent garden, which is characterized in that the method includes preparing a reducing agent to treat a mixture of 33-dimethylbutarate and a compound of the following formula: Η NI / I Η If 2 0 O 『Ho 1 ^ 7 ··· — 1 YIC Η II CO — NH · ~ | <,, --J——ι—r-: — install-- (Please read the first Please fill out this page again) Y and R are the same as defined in item i of the patent application park. 8. The method according to item 7 of the scope of the patent application, characterized in that the reducing agent is an argon gas in the presence of a starting or red-based catalyst at a relative pressure of 1 to 3 bar. 9. The method according to item 7 of the scope of the patent application, characterized in that the reducing agent is sodium cyanoborohydride. Printed by the Central Laboratories of the Ministry of Economic Affairs, Consumer Cooperatives a-paper, one-size-one, one-year, one-year, one-year use Α4 21, one-secret, one-secret 29