Organic compounds

Abstract

This disclosure relates to flavour modification and to compounds of formula (I) ##STR00001## wherein R.sup.1 is selected from C.sub.6-C.sub.13 alky, and C.sub.9-C.sub.13 alkenyl, and R.sup.2 is selected from CH.sub.2-phenyl, CH.sub.2-1H-indole, CH.sub.2-phenol, and CH.sub.2-imidazol,
useful in modifying flavours.

Claims

1. A flavour composition comprising a flavour co-ingredient, and a compound selected from: (Z)-2-(dodec-5-enamido)-3-phenylpropanoic acid, and/or edible salt thereof, and, (Z)-2-(dodec-5-enamido)-3-(1H-indol-3-yl)propanoic acid, and/or edible salt thereof, wherein said compound imparts a flavor modifying characteristic when the compound is present within an ingestible composition in a concentration of 1 ppb-10 ppm.

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: (Z)-2-(dodec-5-enamido)-3-phenylpropanoic acid, and/or edible salt thereof, and, (Z)-2-(dodec-5-enamido)-3-(1H-indol-3-yl)propanoic acid, and/or edible salt thereof, wherein said compound imparts a flavor modifying characteristic when the compound is present within an ingestible composition in a concentration of 1 ppb-10 ppm.

4. A method of modifying the taste of comestible composition comprising at least one flavour co-ingredient comprising the step of: including within the comestible composition a compound selected from: (Z)-2-(dodec-5-enamido)-3-phenylpropanoic acid, and/or edible salt thereof, and, (Z)-2-(dodec-5-enamido)-3-(1H-indol-3-yl)propanoic acid, and/or edible salt thereof, wherein said compound imparts a flavor modifying characteristic when the compound is present within an comestible composition in a concentration of 1 ppb-10 ppm.

5. A method of modifying the taste of a comestible product, the method comprising the step of: including within the comestible product a compound selected from: (Z)-2-(dodec-5-enamido)-3-phenylpropanoic acid, and/or edible salt thereof, and, (Z)-2-(dodec-5-enamido)-3-(1H-indol-3-yl)propanoic acid, and/or edible salt thereof, wherein said compound imparts a flavor modifying characteristic when the compound is present within an comestible product in a concentration of 1 ppb-10 ppm.

Description

EXAMPLE 1

(Z)-2-(Dodec-5-enamido)-3-phenylpropanoic acid (GR-72-7877)

(1) To a cooled mixture (15 C.) of phenylalanine methyl ester HCl (1.20 g, 5.55 mmol) in dichloromethane, anhydrous (100 ml), triethylamine (0.7 ml, 5.04 mmol) and (Z)-dodec-5-enoic acid (1.00 g, 5.04 mmol) each was slowly added. A solution of dicyclohexylcarbodiimide (1.04 g, 5.04 mmol) in dichloromethane (10 ml) was added dropwise in 5 minutes. The reaction was stirred while warming up to room temperature by itself and continued stirring for 16 hours. After filtration, the liquid filtrate was washed with sodium bicarbonate solution (10%), hydrochloric acid (1N), water and brine. The organic layer was dried over sodium sulfate and concentrated under vacuum giving crude solid residue (2 g) that was chromatographed by an 80 g silica column with hexane and ethyl acetate as the eluents. The amidomethyl ester immediate recovered as a colorless liquid 0.83 g. Sodium hydroxide (37%, 1.00 g, 9.23 mmol) was added slowly, and the reaction was stirred at room temperature for 16 hours. The reaction was diluted with water (50 ml) and ethyl acetate (20 ml), and acidified with hydrochloric acid (conc., 0.8 ml) to pH 3. The mixture was extracted three times with ethyl acetate, 30 ml each. The combined extracts were washed with water (20 ml) and brine (20 ml); dried over sodium sulfate; and concentrated under vacuum. The amino acid was recovered as a white solid 0.71 g (2 mmol, 86% yield).

(2) Characterize of the synthesized compound

(3) .sup.1H NMR (300 MHz, DMSO-d6) ppm 0.80-0.91 (m, 3H), 1.20-1.33 (m, 8H), 1.37-1.50 (m, 2H), 1.82-1.99 (m, 4H), 2.00-2.10 (m, 2H), 2.84 (dd, J=13.75, 9.80 Hz, 1H), 3.05 (dd, J=13.85, 4.80 Hz, 1H), 4.42 (ddd, J=9.70, 8.19, 4.71 Hz, 1H), 5.15-5.43 (m, 2H), 7.04-7.36 (m, 5H), 8.10 (d, J=8.29 Hz, 1H), 12.62 (s, 1H).

(4) .sup.13C NMR (75 MHz, DMSO-d6) ppm 173.14, 171.94, 137.74, 129.99, 129.05, 129.00, 128.04, 128.04, 126.28, 53.23, 36.71, 34.61, 31.11, 29.05, 28.26, 26.55, 26.13, 25.30, 22.04, 13.91. MS-APCI [M+H].sup.+: m/z 346.3.

EXAMPLE 2

(Z)-2-(Dodec-5-enamido)-3-(4-hydroxyphenyl)propanoic acid (GR-72-7888)

(5) According to the same procedure of Example 1, (Z)-2-(dodec-5-enamido)-3-(4-hydroxyphenyl)propanoic acid was prepared from (Z)-dodec-5-enoic acid and tyrosine in a yield of 68%.

(6) .sup.1H NMR (300 MHz, DMSO-d6) ppm 0.81-0.91 (m, 3H), 1.20-1.34 (m, 8H), 1.45 (quin, J=7.44 Hz, 2H), 1.86-2.01 (m, 4H), 2.02-2.11 (m, 2H), 2.72 (dd, J=13.85, 9.51 Hz, 1H), 2.91 (dd, J=13.75, 4.90 Hz, 1H), 4.25-4.39 (m, 1H), 5.13-5.45 (m, 2H), 6.51-6.74 (m, 2H), 6.88-7.11 (m, 2H), 8.02 (d, J=7.91 Hz, 1H), 9.17 (br. s., 1H), 12.55 (br. s., 1H).

(7) .sup.13C NMR (75 MHz, DMSO-d6) ppm 173.27, 171.94, 155.82, 130.02, 129.89, 129.89, 129.05, 127.70, 114.86, 114.86, 53.64, 35.99, 34.61, 31.11, 29.06, 28.26, 26.55, 26.18, 25.32, 22.04, 13.91. MS-APCI [M+H].sup.+: m/z 362.1

EXAMPLE 3

2-(Dodecanoylamino)-3-phenylpropanoic acid (GR-72-7558)

(8) According to the same procedure of Example 1, 2-(dodecanoylamino)-3-phenylpropanoic acid was prepared from dodecanoylchloride and phenylalanine in a yield of 88%.

(9) .sup.1H NMR (600 MHz, DMSO-d.sub.6) ppm 0.85 (t, J=6.87 Hz, 3H, HC(12)) 0.99-1.30 (m, 16H, HC(4, 5, 6, 7, 8, 9, 10, 11) 1.36 (quin, J=7.30 Hz, 2H, HC(3)) 2.01 (t, J=7.22 Hz, 2H, HC(2))) 2.83 (dd, J=13.75, 9.62 Hz, 1H, HC(15)) 3.06 (dd, J=13.75, 4.47 Hz, 1H, HC(15)) 4.38 (ddd, J=9.45, 8.25, 4.64 Hz, 1H, HC(14)) 7.08-7.29 (m, 5H, HC(17, 18, 19, 20, 21)) 7.98 (d, J=8.25 Hz, 1H, HN(22))

(10) .sup.13C NMR (150 MHz, DMSO-d.sub.6) ppm 13.95 (C(12)), 22.11 (C(11)), 28.28-29.18 (C(4, 5, 6, 7, 8, 9) 31.31 (C(10)), 35.20 (C(2)), 36.95 (C(15)), 53.71 (C(14)), 126.10 (C((19)), 127.94 (C(18, 20)) 129.13 (C(17, 21)), 138.16 C(16)), 171.91 (C(1)), 173.49 (C(13))

EXAMPLE 4

2-(dodecanoylamino)-3-(1H-indol-3-yl)propanoic acid (GR-72-7557)

(11) According to the same procedure of Example 1, 2-(dodecanoylamino)-3-(1H-indol-3-yl)propanoic acid was prepared from dodecanoylchloride and tryptophane in a yield of 76%.

(12) .sup.1H NMR (600 MHz, DMSO-d.sub.6) ppm 0.79-0.92 (m, 3H, HC(12)) 1.05-1.32 (m, 16H, HC(4, 5, 6, 7, 8, 9, 10, 11) 1.40 (quin, J=7.05 Hz, 2H, HC(3)) 1.95-2.13 (m, 2H, HC(2)) 2.99 (dd, J=14.43, 8.94 Hz, 1H, HC(15)) 3.15 (dd, J=14.61, 4.98 Hz, 1H, HC(15)) 4.47 (td, J=8.42, 5.16 Hz, 1H, HC(14)) 6.93-7.00 (t, J=7.39 Hz, 1H, HC(19)) 7.05 (t, J=7.39 Hz, 1H, HC(20) 7.12 (d, J=2.41 Hz, 1H, HC(23)) 7.32 (d, J=7.56 Hz, 1H, HC(21)) 7.52 (d, J=7.56 Hz, 1H, HC(18)) 8.06 (d, J=7.90 Hz, 1H, HN(25))

(13) .sup.13C NMR (150 MHz, DMSO-d.sub.6) ppm 13.97 (C(12)), 22.13 (C(11)), 26.91-29.25 (C(4, 5, 6, 7, 8, 9, 15), 31.33 (C(10)), 35.12 (C(2)), 52.86 (C(14)), 110.04 (C(16)), 111.35 (C(21)), 118.17 (C(18)), 118.29 (C(19)), 120.86 (C(20)), 123.50 (C(23)), 127.22 (C(17)), 136.10 (C(22)), 172.24 (C(1)). 173.61 (C(13))

EXAMPLE 5

2-(Dodecanoylamino)-3-(4-hydroxyphenyl)propanoic acid (GR-72-7732)

(14) According to the same procedure of Example 1, 2-(dodecanoylamino)-3-(4-hydroxyphenyl)propanoic acid was prepared from dodecanoylchloride and tyrosine in a yield of 5%.

(15) .sup.1H NMR (600 MHz, DMSO-d.sub.6) ppm 0.85 (t, J=6.70 Hz, 3H, HC(12)) 1.09-1.31 (m, 16H) 1.35-1.43 (m, 2H, HC(3)) 1.98-2.06 ((t, J=7.22 Hz, 2H, HC(2)) 2.71 (dd, J=13.92, 9.79 Hz, 1H, HC15)) 2.91 (dd, J=13.92, 4.64 Hz, 1H, HC(15) 4.31 (td, J=8.76, 4.81 Hz, 1H, HC(14)) 6.63 (d, J=8.59 Hz, 2H, HC(18, 20) 6.95-7.02 (d, J=8.59 Hz, 2H, HC(17, 21)) 8.00 (d, J=8.25 Hz, 1H, HN(22))

(16) .sup.13C NMR (150 MHz, DMSO-d.sub.6) ppm 13.97 (C(12)), 22.13 (C(11)), 25.22 (C(3)), 28.35-29.17 C((4, 5, 6, 7, 8, 9)) 31.33 (C(10)), 35.11 (C(2)), 36.07 (C(15)), 53.71 (C(14)), 114.88 C((18, 20)), 127.80 (C(16)), 129.96 (C(17, 21)) 155.86 (C(19)), 172.14 (C(1)), 173.40 (C(13))

EXAMPLE 6

(Z)-2-(dodec-5-enamido)-3-(1H-indol-3-yl)propanoic acidGR72-7759

(17) According to the same procedure of Example 1, (Z)-2-(dodec-5-enamido)-3-(1H-indol-3-yl)propanoic acid was prepared from (Z)-dodec-5-enoic acid and tryptohane in a yield of 10%.

(18) .sup.1H NMR (600 MHz, DMSO-d6) ppm 0.82-0.87 (m, 3H, HC(12)) 1.19-1.30 (m, 8H, HC(8, 9, 10, 11) 1.40-1.50 (m, 2H, 2) 1.88-1.97 (m, 4H, HC(4, 7)) 2.01-2.12 (m, 2H, HC(2)) 2.98 (dd, J=14.61, 8.76 Hz, 1H, HC(15)) 3.15 (dd, J=14.78, 5.15 Hz, 1H, HC15)) 4.44 (td, J=8.16, 4.98 Hz, 1H, HC(14)) 5.25-5.36 (m, 2H, HC(5, 6)) 6.94-6.98 (t, J=6.87 Hz, 1H, HC(20)) 7.03-7.07 (t, J=6.87 Hz, 1H, HC(21)) 7.11 (d, J=2.06 Hz, 1H, HC(17)) 7.31 (d, J=7.90 Hz, 1H, HC(19)) 7.52 (d, J=7.90 Hz, 1H,HC(22)) 8.03 (d, J=7.56 Hz, 1H, HN(24))

(19) .sup.13C NMR (150 MHz, DMSO-d6) ppm 13.95 (C(12)), 22.08 (C(11)), 24.81-29.37 (C(3, 4, 7, 8, 9, 15), 31.15 (C(10)), 34.68 (C(2)), 52.98 (C(14)), 110.13 (C(16)), 111.31 (C(22)), 118.19 (C(19)), 118.26 (C(20)), 120.84 (C(21)), 123.43 (C(17)), 127.25 (C(18)), 129.10 C(5)), 130.06 (C(6)), 136.05 (C(23)), 171.95 (C(1)), 173.58 (C(13))

EXAMPLE 7

3-(1H-indol-3-yl)-2-tetradecanamidopropanoic acid

(20) According to the same procedure of Example 1, 3-(1H-indol-3-yl)-2-tetradecanamidopropanoic acid was prepared from myristoyl chloride and tryptophane in a yield of 19%.

(21) .sup.1H NMR (600 MHz, CHLOROFORM-d) ppm 0.88 (t, J=7.05 Hz, 3H) 1.09-1.36 (m, 21H) 1.43-1.55 (m, 2H) 2.07 (t, J=7.73 Hz, 2H) 3.22-3.41 (m, 2H) 4.71-4.97 (m, 1H) 6.11 (d, J=7.56 Hz, 1H) 6.97 (s, 1H) 7.02-7.14 (m, 1H) 7.18 (t, J=7.56 Hz, 1H) 7.26 (s, 1H) 7.32 (d, J=7.90 Hz, 1H) 7.55 (d, J=7.90 Hz, 1H) 8.34 (br. s., 1H)

(22) .sup.13C NMR (151 MHz, CHLOROFORM-d) ppm 14.11 (s, 1C) 22.68 (s, 1C) 25.38 (s, 1C) 27.03 (s, 1C) 29.15 (s, 1C) 29.28 (s, 1C) 29.36 (s, 1C) 29.45 (s, 1C) 29.62 (s, 1C) 29.65 (s, 1C) 29.69 (s, 1C) 31.91 (s, 1C) 36.40 (s, 1C) 53.37 (s, 1C) 109.52 (s, 1C) 111.40 (s, 1C) 118.37 (s, 1C) 119.70 (s, 1C) 122.18 (s, 1C) 123.20 (s, 1C) 127.75 (s, 1C) 136.08 (s, 1C) 174.28 (s, 1C) 175.17 (s, 1C)

EXAMPLE 8

Beef Bouillon

(23) A beef bouillon was prepared using bouillon cubes obtained from a local supermarket. The drinks were evaluated by a panel of experienced tasters. a) When 40 ppb of (Z)-2-(dodec-5-enamido)-3-phenylpropanoic acid was added to the bouillon the panel agreed that the bouillon tasted more umami, slightly more sweet, and the overall flavor profile lasts longer than the reference. b) When 40 ppb of (Z)-2-(dodec-5-enamido)-3-(4-hydroxyphenyl)propanoic acid was added to the bouillon the panel agreed that the bouillon tasted slightly more umami, slightly more bitter and sweeter than the reference.

EXAMPLE 9

Dairy

(24) A milk drink was prepared using semi skim milk from a local supermarket. a) When 5 ppm of (Z)-2-(dodec-5-enamido)-3-(1H-indol-3-yl)propanoic acid was added to the milk drink the panel agreed that the milk drink tasted slightly increased creamy than the reference. b) When 5 ppm of 3-(1H-indol-3-yl)-2-tetradecanamidopropanoic acid was added to the milk the panel agreed the milk drink had a very creamy aftertaste, and a nice and slightly dryness at the front compared to the reference.

EXAMPLE 10

Umami Base Flavour

(25) An aqueous solution of an umami base flavor was prepared using NaCl, MSG and ribo nucleotides a) When 50 ppm of 2-(dodecanoylamino)-3-phenylpropanoic acid was added to the flavour, the panel agreed that the base tasted more umami, and thicker, possessed a lot of mouthfeel and a nice body, and provided a cleaner taste than the reference. b) When 5 ppm of (Z)-2-(dodec-5-enamido)-3-(1H-indol-3-yl)propanoic acid was added to the flavour, the panel agreed the base tasted more umami than the reference. c) When 20 ppm of 2-(dodecanoylamino)-3-(1H-indol-3-yl)propanoic acid was added to the flavour, the panel agreed the base tasted more fatty mouthfeel than the reference. d) When 5 ppm of 3-(1H-indol-3-yl)-2-tetradecanamidopropanoic acid was added to the base, the panel agreed the base tasted more umami than the reference

EXAMPLE 11

Soy Sauce

(26) A soy sauce was prepared by diluting a soy sauce obtained from a local supermarket. a) When 5 ppm of 3-(1H-indol-3-yl)-2-tetradecanamidopropanoic acid was added to the soy sauce, the panel agreed the sauce taste more mouthfeel, and fuller compared to the reference.