Organic compounds

Abstract

This disclosure relates to flavour modification and to compounds of formula (I) ##STR00001## wherein X is (CH.sub.2).sub.m wherein m is an integer from 7 to 10, or X is C.sub.7-C.sub.10 alkenyl, and i) n is 1, R.sup.1 and R.sup.3 are hydrogen, and R.sup.2 is the residue of a proteinogenic amino acid; ii) n is 1, R.sup.2 is hydrogen, and R.sup.1 and R.sup.3 together are CH.sub.2CH.sub.2CH.sub.2; or iii) n is 2 or 3 and R.sup.1, R.sup.2 and R.sup.3 are hydrogen,
useful in modifying flavours.

Claims

1. A flavour composition comprising a flavour co-ingredient, and a compound of selected from: 9-((1-carboxy-2-(1H-indol-3-yl)ethyl)amino)-9-oxononanoic acid and/or edible salt thereof; 1-(8-carboxyoctanoyl)pyrrolidine-2-carboxylic acid and/or edible salt thereof; and, 9-((3-carboxypropyl)amino)-9-oxononanoic acid and/or edible salt thereof.

2. A flavour composition according to claim 1 wherein the flavour co-ingredient is selected from: sugars, fats, salts, monosodium glutamate, calcium ions, phosphate ions, organic acids, proteins, purines, flavours, and mixtures thereof.

3. A comestible product comprising a compound selected from: 9-((1-carboxy-2-(1H-indol-3-yl)ethyl)amino)-9-oxononanoic acid and/or edible salt thereof; 1-(8-carboxyoctanoyl)pyrrolidine-2-carboxylic acid and/or edible salt thereof; and, 9-((3-carboxypropyl)amino)-9-oxononanoic acid and/or edible salt thereof.

4. A method of modifying the taste of comestible composition comprising at least one flavour co-ingredient, the method comprising the step of: adding to or including in said composition a compound selected from: 9-((1-carboxy-2-(1H-indol-3-yl)ethyl)amino)-9-oxononanoic acid and/or edible salt thereof; 1-(8-carboxyoctanoyl)pyrrolidine-2-carboxylic acid and/or edible salt thereof; and, 9-((3-carboxypropyl)amino)-9-oxononanoic acid and/or edible/salt thereof.

Description

EXAMPLE 1

9-((1-Carboxy-2-(1H-indol-3-yl)ethyl)amino)-9-oxononanoic acid

(1) To a methanol solution (300 ml) was added dropwise acetyl chloride (36 ml, 500 mol). Tryptophan (41.00 g, 201 mmol) was added in portions, and the mixture was stirred at 70 C. for 8 hours. The reaction solution was concentrated under vacuum until white solid was formed, and the mixture was cooled in an ice bath. To a mixture of tryptophan methyl ester hydrochloride (0.45 g, 1.74 mmol) in water (5 ml) was added sodium bicarbonate (0.15 g, 1.74 mmol) and dropwise the solution of 1-(2,5-dioxopyrrolidin-1-yl) 9-methyl nonanedioate (1.00 g, 52%, 1.74 mmol) in 1,4-dioxane (10 ml). After the reaction was stirred at room temperature for 16 hours, it was concentrated under vacuum giving an opaque liquid residue that was dissolved with water (20 ml) and acidified to pH 4 with hydrochloric acid (6N), which was then extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate and concentrated under vacuum giving an orange liquid residue that was purified using silica column with hexane and ethyl acetate (0.01% formic acid) as the solvents giving a colorless liquid product 9-((3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl)amido)-9-oxononanoate. To a mixture of methyl 9-((3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl)amido)-9-oxononanoate (0.64 g, 1.59 mmol) in ethanol (5 ml) and water (5 ml) was added slowly a sodium hydroxide solution (37%, 0.69 g, 6.36 mmol). After the reaction was stirred at room temperature for 16 hours, it was diluted with water (25 ml) and acidified to pH 3 with hydrochloric acid (37%, 0.5 ml), which was then extracted with ethyl acetate. The combined extracts were washed with water and brine; dried over sodium sulfate and concentrated under vacuum giving a residue that was subjected to lyophilization giving a white solid product (0.54 g, 1.44 mmol, 91% yield). MS-APCI (+): m/z [M+H].sup.+ 375.0.

(2) .sup.1H NMR (300 MHz, DMSO-d6) ppm 1.10-1.26 (m, 6H) 1.34-1.53 (m, 4H) 1.99 (s, 1H) 2.06 (t, J=7.25 Hz, 2H) 2.18 (t, J=7.35 Hz, 2H) 2.94-3.05 (m, 1H) 3.14 (d, J=4.90 Hz, 1H) 4.47 (td, J=8.29, 5.09 Hz, 1H) 6.94-7.02 (m, 1H) 7.02-7.10 (m, 1H) 7.13 (d, J=2.26 Hz, 1H) 7.33 (d, J=7.91 Hz, 1H) 7.53 (d, J=7.72 Hz, 1H) 8.03 (d, J=7.91 Hz, 1H) 10.82 (s, 1H) 12.26 (br. s., 1H). .sup.13C NMR (75 MHz, DMSO-d6) ppm 174.47, 173.56, 172.13, 136.04, 127.17, 123.43, 120.83, 118.26, 118.12, 111.29, 110.01, 52.78, 35.02, 33.63, 28.46, 28.39, 28.36, 27.09, 25.07, 24.44.

EXAMPLE 2

1-(8-Carboxyoctanoyl)pyrrolidine-2-carboxylic acid

(3) To a mixture of proline methyl ester hydrochloride (0.58 g, 3.47 mmol) in water (5 ml) was added sodium bicarbonate (0.29 g, 3.47 mmol) and dropwise the solution of 1-(2,5-dioxopyrrolidin-1-yl) 9-methyl nonanedioate (2.00 g, 52%, 3.47 mmol) in 1,4-dioxane (10 ml). After the reaction was stirred at room temperature for 16 hours, it was concentrated under vacuum giving an opaque liquid residue that was dissolved with water (20 ml) and acidified to pH 4 with hydrochloric acid (6N), which was then extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate and concentrated under vacuum giving colorless liquid residue that was purified using 40 g silica column with hexane and ethyl acetate (0.01% formic acid) as the solvents giving a colorless liquid product Methyl 1-(9-methoxy-9-oxononanoyl)pyrrolidine-2-carboxylate. To a mixture of methyl 1-(9-methoxy-9-oxononanoyl)pyrrolidine-2-carboxylate (0.64 g, 2.20 mmol) in ethanol (11 ml) and water (11 ml) was added slowly sodium hydroxide solution (37%, 0.95 g, 8.81 mmol). After the reaction was stirred at room temperature for 16 hours, it was diluted with water (50 ml), and acidified to pH 3 with hydrochloric acid (37%, 0.7 ml), which was then extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate and concentrated under vacuum giving a residue that was subjected to lyophilization giving a white solid product (0.61 g, 2.14 mmol, 97% yield). MS-APCI(+): m/z [M+H].sup.+ 286.1.

(4) .sup.1HNMR (300 MHz, DMSO-d6) ppm 1.18-1.33 (m, 6H) 1.48 (br. s., 4H) 1.76-1.95 (m, 2H) 2.14-2.31 (m, 4H) 3.37 (d, J=7.16 Hz, 2H) 3.45-3.55 (m, 2H) 4.20 (add, J=8.67, 3.58 Hz, 1H). .sup.13C NMR (75 MHz, DMSO-d6) ppm 174.45, 173.94, 173.55, 170.82, 170.62, 58.62, 58.18, 46.43, 33.61, 33.43, 28.78, 28.57, 28.50, 28.43, 24.43, 24.31, 24.14.

EXAMPLE 3

9-((3-Carboxypropyl)amino)-9-oxononanoic acid

(5) To a mixture of 4-aminobutyric acid methyl ester hydrochloride (0.53 g, 3.47 mmol) in water (5 ml) was added sodium bicarbonate (0.29 g, 3.47 mmol) and dropwise the solution of 1-(2,5-dioxopyrrolidin-1-yl) 9-methyl nonanedioate (2.00 g, 52%, 3.47 mmol) in 1,4-dioxane (10 ml). After the reaction was stirred at room temperature for 16 hours, it was concentrated under vacuum giving an opaque liquid residue that was dissolved with water (20 ml) and acidified to pH 4 with hydrochloric acid (6N), which was then extracted with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate and concentrated under vacuum giving an orange liquid residue that was purified using silica column with hexane and ethyl acetate as the solvents (0.01% formic acid) as the solvents giving a colorless liquid product Methyl 9-((4-methoxy-4-oxo butyl)amino)-9-oxononanoate. To a mixture of methyl 9-((4-methoxy-4-oxo butyl)amino)-9-oxononanoate (0.64 g, 2.12 mmol) in ethanol (11 ml) and water (11 ml) was added slowly sodium hydroxide solution (37%, 0.92 g, 8.49 mmol). After the reaction was stirred at room temperature for 16 hours, it was diluted with water (50 ml), and acidified to pH 3 with hydrochloric acid (37%), which was then extracted with ethyl acetate. The combined extracts were washed with brine (20 ml), dried over sodium sulfate and concentrated under vacuum giving a residue that was subjected to lyophilization giving a white solid product (0.43 g, 1.57 mmol, 74% yield). MS-APCl (+): m/z [M+H].sup.+ 274.1.

(6) .sup.1HNMR (300 MHz, DMSO-d6) ppm 1.16-1.30 (m, 6H) 1.40-1.53 (m, 4H) 1.60 (quint, J=7.16 Hz, 2H) 2.03 (t, J=7.35 Hz, 2H) 2.20 (td, J=7.35, 5.09 Hz, 4H) 2.97-3.08 (m, 2H) 7.76 (t, J=5.46 Hz, 1H) 11.99 (s, 2H). .sup.13C NMR (75 MHz, DMSO-d6) ppm 174.44, 174.15, 171.99, 37.73, 35.33, 33.60, 31.01, 28.48, 28.40, 25.20, 24.60, 24.43.

EXAMPLE 4

Beef Bouillon

(7) A beef bouillon was prepared using bouillon cubes obtained from a local supermarket.

(8) The drinks were evaluated by a panel of experienced tasters. a) When 40 ppb of 9-((1-carboxy-2-(1H-indol-3-yl)ethyl)amino)-9-oxononanoic acid (Example 1) was dosed to the bouillon the panel agreed that this drink tasted more umami, more salty and more full than the reference. b) When 40 ppb of 1-(8-carboxyoctanoyl)pyrrolidine-2-carboxylic acid (Example 2) was dosed to the bouillon the panel agreed that this drink had more salt impact, and more umami taste than the reference. c) When 40 ppb of 9-((3-Carboxypropyl)amino)-9-oxononanoic acid (Example 3) was dosed to the bouillon the panel agreed that this drink tasted more salty and had more bite than the reference.