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.2-C.sub.20 alkyl, and C.sub.6-C.sub.25 alkenyl, and a) R.sup.2 and R.sup.3 together are —C(O)CH.sub.2CH.sub.2—; or b) R.sup.3 is hydrogen and R.sup.2 is —CH.sub.2CH.sub.2C(O)NHCH.sub.2CH.sub.3,

useful in modifying flavours.

Claims

1. A flavour composition comprising a flavour co-ingredient and a compound of formula (I) ##STR00003## wherein R.sup.1 is selected from C.sub.2-C.sub.20 alkyl, and C.sub.6-C.sub.25 alkenyl, and a) R.sup.2 and R.sup.3 together are —C(O)CH.sub.2CH.sub.2—; or b) R.sup.3 is hydrogen and R.sup.2 is —CH.sub.2CH.sub.2C(O)NHCH.sub.2CH.sub.3.

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 of formula (I) ##STR00004## wherein R.sup.1 is selected from C.sub.2-C.sub.20 alkyl, and C.sub.6-C.sub.25 alkenyl, and a) R.sup.2 and R.sup.3 together are —C(O)CH.sub.2CH.sub.2—; or b) R.sup.3 is hydrogen and R.sup.2 is —CH.sub.2CH.sub.2C(O)NHCH.sub.2CH.sub.3.

4. A compound of formula (I) ##STR00005## wherein R.sup.1 is selected from C.sub.2-C.sub.20 alkyl, and C.sub.6-C.sub.25 alkenyl, and a) R.sup.2 and R.sup.3 together are —C(O)CH.sub.2CH.sub.2—; or, b) R.sup.3 is hydrogen and R.sup.2 is —CH.sub.2CH.sub.2C(O)NHCH.sub.2CH.sub.3.

5. 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 the said composition a compound of formula (I) ##STR00006## wherein R.sup.1 is selected from C.sub.2-C.sub.20 alkyl, and C.sub.6-C.sub.25 alkenyl, and a) R.sup.2 and R.sup.3 together are —C(O)CH.sub.2CH.sub.2—; or b) R.sup.3 is hydrogen and R.sup.2 is —CH.sub.2CH.sub.2C(O)NHCH.sub.2CH.sub.3.

6. A taste-modifying agent adapted for use in a consumable product, the taste-modifying agent comprising of a compound of formula (I) ##STR00007## wherein R.sup.1 is selected from C.sub.2-C.sub.20 alkyl, and C.sub.6-C.sub.25 alkenyl, and a) R.sup.2 and R.sup.3 together are —C(O)CH.sub.2CH.sub.2—; or b) R.sup.3 is hydrogen and R.sup.2 is —CH.sub.2CH.sub.2C(O)NHCH.sub.2CH.sub.3.

7. A flavor composition according to claim 1, wherein the compound of Formula (I) is selected from: 5-(ethylamino)-2-oleamido-5-oxopentanoic acid; 2-butylamido-5-(ethylamino)-5-oxopentanoic acid; 5-(ethylamino)-2-hexanamido-5-oxopentanoic acid: 5-(ethylamino)-2-isobutyramido-5-oxopentanoic acid; 5-(ethylamino)-2-[(9Z,12Z)-octadeca-9,12-dienoylamino]-5-oxopentanoic acid; 5-(ethylamino)-2-dodecanamido-5-oxopentanoic acid; 5-oxo-1-palmitoylpyrrolidine-2-carboxylic acid; and, 5-oxo-1-stearoylpyrrolidine-2-carboxylic acid.

8. A compound according to claim 4, wherein the compound of Formula (I) is selected from: 5-(ethylamino)-2-oleamido-5-oxopentanoic acid; 2-butylamido-5-(ethylamino)-5-oxopentanoic acid; 5-(ethylamino)-2-hexanamido-5-oxopentanoic acid: 5-(ethylamino)-2-isobutyramido-5-oxopentanoic acid; 5-(ethylamino)-2-[(9Z,12Z)-octadeca-9,12-dienoylamino]-5-oxopentanoic acid; 5-(ethylamino)-2-dodecanamido-5-oxopentanoic acid; 5-oxo-1-palmitoylpyrrolidine-2-carboxylic acid; and, 5-oxo-1-stearoylpyrrolidine-2-carboxylic acid.

9. A comestible product according to claim 3, wherein the compound of Formula (I) is selected from: 5-(ethylamino)-2-oleamido-5-oxopentanoic acid; 2-butylamido-5-(ethylamino)-5-oxopentanoic acid; 5-(ethylamino)-2-hexanamido-5-oxopentanoic acid: 5-(ethylamino)-2-isobutyramido-5-oxopentanoic acid; 5-(ethylamino)-2-[(9Z,12Z)-octadeca-9,12-dienoylamino]-5-oxopentanoic acid; 5-(ethylamino)-2-dodecanamido-5-oxopentanoic acid; 5-oxo-1-palmitoylpyrrolidine-2-carboxylic acid; and, 5-oxo-1-stearoylpyrrolidine-2-carboxylic acid.

9. A method according to claim 5, wherein the compound of Formula (I) is selected from: 5-(ethylamino)-2-oleamido-5-oxopentanoic acid; 2-butylamido-5-(ethylamino)-5-oxopentanoic acid; 5-(ethylamino)-2-hexanamido-5-oxopentanoic acid: 5-(ethylamino)-2-isobutyramido-5-oxopentanoic acid; 5-(ethylamino)-2-[(9Z,12Z)-octadeca-9,12-dienoylamino]-5-oxopentanoic acid; 5-(ethylamino)-2-dodecanamido-5-oxopentanoic acid; 5-oxo-1-palmitoylpyrrolidine-2-carboxylic acid; and, 5-oxo-1-stearoylpyrrolidine-2-carboxylic acid.

10. A taste-modifying agent of claim 6, wherein the compound of Formula (I) is selected from: 5-(ethylamino)-2-oleamido-5-oxopentanoic acid; 2-butylamido-5-(ethylamino)-5-oxopentanoic acid; 5-(ethylamino)-2-hexanamido-5-oxopentanoic acid: 5-(ethylamino)-2-isobutyramido-5-oxopentanoic acid; 5-(ethylamino)-2-[(9Z,12Z)-octadeca-9,12-dienoylamino]-5-oxopentanoic acid; 5-(ethylamino)-2-dodecanamido-5-oxopentanoic acid; 5-oxo-1-palmitoylpyrrolidine-2-carboxylic acid; and, 5-oxo-1-stearoylpyrrolidine-2-carboxylic acid.

Description

EXAMPLE 1

5-(ethylamino)-2-oleamido-5-oxopentanoic acid (C18:1 Theanine)

[0113] To a solution of theanine (1.09 g, 6.26 mmol) in 1:1 THF: 1N NaOH (30 ml:30 ml) at room temperature was added oleoyl chloride (1.88 g, 6.26 mmol) dropwise. The reaction was stirred at room temperature for 5 hours. THF was removed under vacuum. To this aqueous layer, conc. HCl was used to adjust the pH to 2. The aqueous layer was then extracted with EtOAc 3× and the organic layers were combined. The organic layer was washed with water, brine, dried (Na.sub.2SO.sub.4) and concentrated. The residue was chromatographed on silica gel (5% MeOH/DCM, 0.1% formic acid) to give 1.32 g (45.7%) of the product as a white paste.

[0114] .sup.1H NMR (300 MHz, CD.sub.3OD) δ ppm 0.92 (t, J=7.2 Hz, 3H), 1.13 (t, J=7.2 Hz, 3H), 1.32-1.36 (m, 21H), 1.58-1.68 (m, 2H), 1.89-2.26 (m, 10H), 3.18-3.32 (m, 2H), 4.39 (d,d, J=9.6, 4.5 Hz, 1H), 5.03-5.42 (m, 2H). .sup.13C NMR (300 MHz, CD.sub.3OD) δ ppm 14.45, 14.76, 23.74, 26.90, 28.14, 28.16, 28.72, 30.25, 30.30, 30.35, 30.37, 30.45, 30.61, 30.85, 33.06, 33.43, 35.29, 36.87, 53.20, 130.82, 130.87, 174.57, 174.93, 176.42.

EXAMPLE 2a-e

[0115] Following the general procedure as described in Examples 1 the following compounds have been prepared:

2a: 2-butylamido-5-(ethylamino)-5-oxopentanoic acid (C4:0 Theanine)

[0116] Yield:37.6%

[0117] .sup.1H NMR (300 MHz, CD.sub.3OD) δ ppm 0.96 (t, J=8.1 Hz, 3H), 1.10 (t, J=7.5 Hz, 3H), 1.59-1.71 (m, 2H), 1.88-1.99 (m, 1H), 2.10-2.30 (m, 5H), 3.18 (q, J=8.4 Hz, 2H), 4.37 (d, d, J=9.0, 4.8 Hz, 1H). .sup.13C NMR (300 MHz, CD.sub.3OD) δ ppm 12.45, 13.33, 18.85, 27.20, 31.98, 33.86, 37.29, 51.77, 173.06, 173.45, 174.77.

2b: 5-(ethylamino)-2-hexanamido-5-oxopentanoic acid (C6:0 Theanine)

[0118] Yield: 50.8%

[0119] .sup.1H NMR (300 MHz, CD.sub.3OD) δ 0.91 (t, J=7.2 Hz, 3H), 1.11 (t, J=6.3 Hz, 3H), 1.30-1.36 (m, 4H), 1.60-1.68 (m, 2H), 1.87-2.00 (m, 1H), 2.10-2.30 (m, 5H), 3.19 (q, J=6.3 Hz, 2H), 4.37 (d, d, J=9.3, 5.4 Hz, 1H). .sup.13C NMR (300 MHz, CD.sub.3OD) δ ppm 12.78, 13.22, 21.90, 25.06, 27.12, 31.00, 31.86, 33.74, 35.30, 51.66173.03, 173.42, 174.93.

2c: 5-(ethylamino)-2-isobutyramido-5-oxopentanoic acid (C4:0-Theanine): Yield: 9.34%

[0120] .sup.1H NMR (300 MHz, CD.sub.3OD) δ 1.07-1.14 (m, 9H), 1.89-1.98 (m, 1H), 2.11-2.30 (m, 3H), 2.45-2.56 (m, 1H), 3.19 (q, J=7.2 Hz, 2H), 4.36 (d, d, J=8.1, 4.2 Hz, 1H). .sup.13C NMR (300 MHz, CD.sub.3OD) δ ppm 13.23, 18.24, 18.30, 27.11, 31.89, 33.77, 34.54, 51.61, 173.08, 173.47, 178.76.

2d: 5-(ethylamino)-2-[(9Z,12Z)-octadeca-9,12-dienoylamino]-5-oxopentanoic acid (C18:2-Theanine)

[0121] Yield: 9.34%

[0122] .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ ppm 0.80-0.89 (t, J=6.83 Hz, 3H, H—C(18)) 0.98 (t, J=7.22 Hz, 3H) 1.18-1.36 (m, 14H, H—C(4, 5, 6, 7, 15, 16, 17) 1.43-1.51 (quin, J=7.56 Hz 2H, H—C(3)) 1.69-1.79 (m, 1H, H—C(21)) 1.88-1.96 (m, 1H, H—C(21)) 2.02 (q, J=6.87 Hz, 4H, H—C(8, 14) 2.06-2.14 (m, 4H, H—C(2, 22)) 2.73 (t, J=6.70 Hz, 2H, H—C(11)) 3.04 (qd, J=7.22, 5.50 Hz, 2H. H—C(24)) 4.12 (ddd, J=9.02, 7.82, 5.16 Hz, 1H, H—C(20)) 5.22-5.38 (m, 4H, (H—C(9, 10, 12, 13) 7.80 (t, J=5.33 Hz, 1H, H—N(27)) 8.04 (d, J=7.56 Hz, 1H, H—N (26))

[0123] .sup.13C NMR (150 MHz, DMSO-d.sub.6) δ ppm 14.45 (C(18)), 15.25 (C(25)), 22.50 (C(17)), 25.74 (C(11)). 27.08-27.22 (C(8, 14)), 27.59 C(21)), 28.76-29.81 (C(3, 4, 5, 6, 7, 15)), 31.42 (C(16)), 32.30 (C(22)), 33.81 (C(24)), 35.60 (C(2)), 52.03 (C(20)), 128.23-128.31 (C(10, 12)), 130.22-130.32 (C(9)), 171.41 (C(23)), 172.80 (C(1)), 174.08 C(19))

2e: 5-(ethylamino)-2-dodecanamido-5-oxopentanoic acid (C12:0 Theanine)

[0124] Yield: 45.7%

[0125] .sup.1H NMR (300 MHz, CD.sub.3OD) δ ppm 0.92 (t, J=7.2 Hz, 3H), 1.13 (t, J=7.2 Hz, 3H), 1.32-1.36 (m, 21H), 1.58-1.68 (m, 2H), 1.89-2.26 (m, 10H), 3.18-3.32 (m, 2H), 4.39 (d,d, J=9.6, 4.5 Hz, 1H), 5.03-5.42 (m, 2H). .sup.13C NMR (300 MHz, CD.sub.3OD) δ ppm 14.45, 14.76, 23.74, 26.90, 28.14, 28.16, 28.72, 30.25, 30.30, 30.35, 30.37, 30.45, 30.61, 30.85, 33.06, 33.43, 35.29, 36.87, 53.20, 130.82, 130.87, 174.57, 174.93, 176.42.

EXAMPLE 3

5-oxo-1-palmitoylpyrrolidine-2-carboxylic acid (C16:0 pyro-Glu)

[0126] A 250 mL reaction flask equipped with a magnetic stirrer bar, a nitrogen inlet, a temperature probe, an addition funnel and a reflux condenser was charged with pyroglutamic acid (11.62 g, 90 mmol), triethylamine (18.21 g, 180 mmol) and acetonitrile (150 mL). The reaction mixture was placed in an ice bath. Then, a solution of palmitoyl chloride (24.74 g, 90 mmol) in acetonitrile (60 mL) was added while maintaining the temperature at approximately 10° C. After removal of the ice bath, the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered over a glass filter and then concentrated on rotary evaporator under reduced pressure. After adding water (150 mL) and 1 M aqueous hydrochloric acid (120 mL), the residue was extracted with ethyl acetate (4×100 mL). The combined organic layers were dried over magnesium sulphate and then concentrated in vacuo. Recrystallisation of the residue from heptane/ethyl acetate=5:4 (90 mL) afforded 5-oxo-1-palmitoylpyrrolidine-2-carboxylic acid in 37% yield (13 g) and a purity >95%.

[0127] .sup.1H NMR (600 MHz, DMSO-d6) δ ppm 0.82 (t, J=6.87 Hz, 3H, H—C(16)) 1.17-1.25 (m, 24H, H—C(4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)) 1.47 (br. s., 2H, H—C(3)) 1.91 (m, 1H, H—C(19))2.26 (m, 1H, H—C(19)) 2.54 (m, 2H, H—C(2)) 2.71-2.79 (m, 2H,H—C(20)) 4.53 (dd, J=9.62, 3.09 Hz, 3H, H—C(18))

[0128] .sup.13C NMR (150 MHz, DMSO-d6) δ ppm 13.95 (C(16)), 20.74 (C(19)), 22.10 (C(15)). 23.73 (C(3)), 28.36-29.18 (C(4, 5, 6, 7, 8, 9, 10, 1, 12, 13)) 31.31 (C(20)) 31.70 (C(14)), 35.85 (C(2)), 57.66 (C(18)), 172.56 (C(21)), 173.11 (C(1)) 174.85 (C(17))

EXAMPLE 4

5-oxo-1-stearoylpyrrolidine-2-carboxylic acid (C18:0 pyro-Glu)

[0129] 5-Oxo-1-stearoylpyrrolidine-2-carboxylic acid was prepared from pyroglutamic acid and stearoyl chloride as described in example 3. Yield was 30%.

[0130] .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ ppm 0.76-0.92 (m, 3H) 1.08-1.34 (m, 28H) 1.47 (br. s., 2H) 1.59-1.83 (m, 1H) 1.83-1.98 (m, 1H) 1.98-2.16 (m, 3H) 2.16-2.32 (m, 3H) 2.50 (s, 1H) 4.10-4.25 (m, 1H)

[0131] .sup.13C NMR (151 MHz, DMSO-d.sub.6) δ ppm 14.48 (s, 1C) 22.62 (s, 1C) 25.76 (s, 1C) 26.88 (s, 1C) 29.11 (s, 1C) 29.24 (s, 1C) 29.34 (s, 1C) 29.51 (s, 1C) 29.53 (s, 1C) 29.57 (s, 1C) 30.65 (s, 1C) 31.82 (s, 1C) 35.57 (s, 1C) 39.63 (s, 1C) 39.77 (s, 1C) 39.90 (s, 1 C) 40.05 (s, 1C) 40.18 (s, 1C) 40.33 (s, 1C) 40.47 (s, 1C) 51.53 (s, 1C) 172.88 (s, 1 C) 173.99 (s, 1C) 174.24 (s, 1C)

EXAMPLE 5

Say Based Products

[0132] Kikkoman low salt soy sauce was diluted 100 times. Part of the solution was kept as the reference. To another part was dosed a compound of formula (I). The solutions were tasted by a professional panel. The results are shown below.

[0133] 5.a: 0.1 ppm of 5-oxo-1-stearoylpyrrolidine-2-carboxylic acid (C18:0 pyro-Glu) was added to tap water containing 1% salt reduced kikoman soy sauce (9% salt). The resultant composition was considered to have more body and to be more umami, more salty, longer lasting and richer than the reference without the compound.

[0134] 5.b: 0.5 ppm of 5-oxo-1-palmitoylpyrrolidine-2-carboxylic acid (C16:0 pyro-Glu) was added to salt reduced kikoman soy sauce (9% salt). The resultant composition was considered to have a stronger saltiness and to be more lingering, more umami.

EXAMPLE 6

Soups and Bouillons

[0135] A compound of formula (I) in a concentration as indicated below was added to a chicken bouillon base (0.7% salt, 0.5% fat). The resultant composition was compared with a chicken bouillon without a compound of formula (I). The results are shown below.

[0136] C16:0 pyro-Glu (0. 5ppm): Nice strong salty, umami lingering body, better meat profile

[0137] C18:0 pyro-Glu (0.2ppm): More umami lingering body, more salty, more rich

[0138] C18:2-Theanine (0.5ppm): More body and fatty notes, salivating

EXAMPLE 7

Snack Products

[0139] A snack product consisting of a fried potato base, containing 35% fat and flavored with cheese seasoning containing salt, MSG, dairy, organic acids, sugars, and a flavour formulation. A compound of formula (I) was added to the snack product at the indicated levels and the tasting results are reported as follows (compared with a snack product without a compound of formula (I)):

[0140] C18:0 pyro-Glu (1ppm): more full, more cheesy, longer lasting, more salty

[0141] C16:0 pyro-Glu (0.5ppm): more rich, more cheesy, more umami. More salty

[0142] C18:2-Theanine (0.1ppm): more fatty, more umami, more succulent

EXAMPLE 8

Caloric & Non Caloric Beverages

[0143] 8.1: Tang powdered soft drink: In an orange flavoured Tang powdered soft drink (market product) sweetened with sucrose plus high intensity sweetener and containing citric acid, C18:0 pyro-Glu, and C18:2-Theanine were tested.

[0144] All samples were evaluated by expert tasters. Tasters were asked to describe the samples focusing on authentic taste, mouthfeel & body, enhancement, richness, juiciness, long lastingness, salivation, sweetness, masking off notes of high intensity sweetener. The results are given below.

[0145] Base (Orange flavoured Tang): sweet, orange, licorice, and lingering high intensity sweetener offnotes, bitter, thin.

[0146] Base (Orange flavoured Tang) plus C18:0 pyro-Glu at 0.1 ppm: enhanced fruitiness, enhanced mouthfeel. Additionally, the off-notes of the high intensity sweetener were suppressed.

[0147] Base (Orange flavoured Tang) plus C18:2Theanine at 1 ppm: enhances sweet juicy orange notes,more body, more mouthfeel. Additionally, the off-notes of the high intensity sweetener were suppressed.

[0148] 8.2: Mango flavoured still beverage: In a Mango flavoured still beverage, sweetened with 8% sucrose & containing 0.1% citric acid and 1% clear mango juice flavoured with proprietary Mango flavour @ 0.05%, C16:0 pyro-Glu and C18:2-Theanine were added, as such (separate) and in combination.

[0149] All samples were evaluated by expert tasters. Tasters were asked to describe the samples focusing on authentic taste, juicy mouthfeel, enhancement, richness, juiciness, long lastingness, salivation, sweetness. The results are given below.

[0150] Base*: sweet, fruity, mango, thin

[0151] Base plus C16:0-pyro-Glu at 0.1 ppm: very juicy and long lasting sweet, salivating

[0152] Base plus C18:2-Theanine at 1 ppm: fatty skin-like, very juicy, authentic mango, more mouthfeel, long lasting mango taste.

[0153] *Base: water, 8% sucrose, 0.1% citric acid, 1% clear mango juice (i.e. very low juice concentration) , flavoured with Mango flavor (dosed at 0.05%).

EXAMPLE 9

Green Tea

[0154] A green tea was brewed by taking 0.6 g of tea/100 ml of water. The water was heated to 80° C. and the tea leaves were left in the solution for 5 minutes. The tea solution was allowed to cool down to room temperature. Part of the solution was kept as a reference. To another part was added a compound of formula (I) in a concentration as indicated below. The solutions were tasted against the reference (i.e. a green tea without a compound of formula (I)). The results are shown below.

[0155] 10 ppb of N-linoleoyl theanine (C18:2 Theanine): more astringent, more body and somewhat more bitter umami than the reference.

[0156] 1 ppb of N-linoleoyl theanine (C18:2 Theanine): more authentic tea than the reference and to have a nice balance between bitterness and astringency.

[0157] 0.2 ppm of 5-oxo-1-stearoylpyrrolidine-2-carboxylic acid (C18:0 pyro-Glu): more complex and had more mouthfeel.

[0158] 0.02 ppm of N-linoleoyl theanine (C18:2 Theanine): the sample had a better green tea character, was less bitter and had a better mouthfeel.