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.20 alkyl, and C.sub.9-C.sub.25 alkenyl, and i) R.sup.3 and R.sup.4 are hydrogen and R.sup.2 the residue of a proteinogenic amino acid; ii) R.sup.2 and R.sup.3 are methyl and R.sup.4 is hydrogen; or R.sup.4 is hydrogen and R.sup.2 and R.sup.3 form together with the carbon atom to which they are attached cyclopropyl; iii) R.sup.2 is hydrogen, and R.sup.3 and R.sup.4 together are CH.sub.2CH.sub.2CH.sub.2,
useful in modifying flavours.

Claims

1. A flavour composition of comprising a flavour co-ingredient and a compound selected from: N-(3-(methylthio)propyl)oleamide and N-(4-amino-4-oxobutyl)oleamide, wherein the flavour composition provides an organoleptic effect to comestible product when the compound is incorporated in a comestible product at a concentration of 1 ppb-1 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. The flavour composition of claim 1, wherein the flavour composition provides an organoleptic effect to a comestible product when the compound is incorporated in a comestible product at a concentration of 1 ppb-500 ppb.

4. A comestible product comprising a compound selected from: N-(3-(methylthio)propyl)oleamide and N-(4-amino-4-oxobutyl)oleamide, wherein the said compound is present in the comestible product at a concentration of 1 ppb-1 ppm.

5. A taste modifying agent for incorporation in a comestible product, the said taste modifying agent comprising a compound selected from: N-(3-(methylthio)propyl)oleamide and N-(4-amino-4-oxobutyl)oleamide, wherein the taste modifying agent is present in the comestible product at a concentration of 1 ppb-1 ppm.

6. The comestible product of claim 4, wherein the comestible product comprises salt or alcohol or coolant compounds, and said compound is present in the comestible product at a concentration of 1-100 ppb.

7. The comestible product of claim 4, wherein the comestible product comprises an umami tastant, and said compound is present in the comestible product at a concentration of 100 ppb-250 ppb.

8. The comestible product of claim 4, wherein the comestible product comprises fats, and said compound is present in the comestible product at a concentration of 500 ppb-1 ppm.

9. The comestible product of claim 4, wherein the comestible product is an alcoholic beverage, and said compound is present in the alcoholic beverage at a concentration of 1 ppb-1 ppm.

10. The comestible product according to claim 4, wherein the comestible product is a beverage containing a sweetener, and said compound is present in the comestible product at a concentration of 1 ppb-10 ppm.

11. The comestible product according to claim 4, wherein the comestible product is a soy-based product or a fish-based product, and said compound is present in the comestible product at a concentration of 1 ppb-10 ppm.

Description

EXAMPLE 1

(Z)-1-(pyrrolidin-1-yl)octadec-9-en-1-one

(1) In a 250 mL round-bottomed flask fitted with a stirrer, cooler and dropping funnel, pyrrolidine (0.851 g, 11.96 mmol) was dissolved in dichloromethane (DCM; 75 ml). Triethylamine (1.668 ml, 11.96 mmol) was added at room temperature. Oleoyl chloride (3 g, 9.97 mmol) was added dropwise while stirring. Exothermic reaction, solution starts to reflux. Stirring was continued for 1 hour. Reaction mixture was diluted with DCM, washed with a diluted aqueous solution of hydrochloric acid and water. Organic layer (under layer) was separated, dried and evaporated.

(2) The oily residue was purified by flash column chromatography (eluent heptane/ethylacetate). 1.9 g of the title compound could be isolated as an oil, purity >95%, yield: 54%.

(3) .sup.1H NMR (600 MHz, DMSO-d.sub.6) ppm 0.73-0.93 (m, 3H, HC(18)) 1.14-1.34 (m, 20H, HC(4, 5, 6, 7, 12, 13, 14, 15, 16, 17)) 1.47 (br. s., 2H, HC(3)) 1.74 (quin, J=6.79 Hz, 2H, HC(20, 21) 1.85 (quin, J=6.79 Hz, 2H, HC(20, 21)) 1.91-2.07 (m, 4H, HC(8, 11)) 2.18 (t, J=7.39 Hz, 2H, HC(2)) 3.25 (t, J=6.87 Hz, 2H, HC(19, 22)) 3.29-3.49 (m, 2H, CH(19, 22) 5.22-5.42 (m, 2H, HC(9,10))

(4) .sup.13C NMR (150 MHz, DMSO-d.sub.6) ppm 13.90 ppm (C(18), 22.09 (C(17)), 23.93 C(20, 21))), 25.64 (C(3)), 26.52-26.65 (C(8, 11)) 28.36-29.35 (C(3, 4, 5, 6, 7, 12, 13, 14, 15)), 31.29 (C16)), 33.74 (C(2)), 5.13 (C(19)), 45.13 (C(19)), 45.81 (C(22)) 129.57 (C(9, 10) 170.18 (C(1))

EXAMPLE 2

N-(3-(methylthio)propyl)oleamide

(5) According to the same procedure of Example 1, N-(3-(methylthio)propyl)oleamide was prepared from oleoyl chloride and 3-(methylthio)propan-1-amine in the presence of triethylamine in a yield of 40%.

(6) .sup.1H NMR (600 MHz, CHLOROFORM-d) ppm 0.87 (t, J=6.70 Hz, 3H, HC(18)) 1.21-1.37 (m, 20H, HC(4, 5, 6, 7, 12, 13, 14, 15, 16, 17) 1.59-1.65 (m, 2H, HC(3)) 1.81 (quin, J=6.96 Hz, 2H, HC(20)) 2.00 (q, J=6.53 Hz, 4H, HC(8, 11))) 2.09 (s, 3H, HC(22)) 2.15-2.20 (t, J=7.59 Hz, 2H, HC(3)) 2.53 (t, J=7.05 Hz, 2H HC(21)) 3.36 (q, J=6.53 Hz, 2H, HC19)) 5.24-5.43 (m, 2H, HC(9, 10) 5.93 (br. s., 1H, HN)

(7) .sup.13C NMR (150 MHz, CHLOROFORM-d) ppm 14.07 (C(18)), 15.43 (C(22)), 22.63 (C(17)), 27.00-27.29 (C(8, 11)) 28.61 (C(20)), 28.88-29.87 (C(3, 4, 5, 6, 7, 12, 13, 14, 15)) 31.68 (C(21)), 31.85 (C(16)), 36.72 (C(2)), 38.60 (C(19)), 128.98-130.32 (C(9, 10)), 173.33 (C(1))

EXAMPLE 3

N-cyclopropyloleamide

(8) According to the same procedure of Example 1, N-cyclopropyloleamide was prepared from oleoyl chloride and cyclopropanaminein the presence of triethylamine in a yield of 15%.

(9) .sup.1H NMR (600 MHz, CHLOROFORM-d) ppm 0.46-0.49 (m, 2H, HC(20, 21)) 0.73-0.77 (m, 2H, HC(20, 21)) 0.87 (t, J=6.87 Hz, 3H, HC(18)) 1.23-1.34 (m, 20H, HC(4, 5, 6, 7, 12, 13, 14, 15, 16, 17) 1.58-1.62 (m, 2H, HC(3)) 2.00 (q, J=6.53 Hz, 4H, HC(8, 11) 2.10-2.13 (m, 2H, HC(2)) 2.69 (dd, J=6.87, 3.78 Hz, 1H, HC(19)) 5.32-5.35 (m, 2H, 9, 10)) 5.66 (b, 1H, HN)

(10) .sup.13C NMR (150 MHz, CHLOROFORM-d) ppm 5.57 (C(20, 21), 13.88 (C(18)), 22.08 (C(17)) 26.52-26.61 (C(8, 11)), 28.20-29.26 (C(3, 4, 5, 6, 7, 12, 13, 14, 15, 16)), 30.62 (C(19)), 35.19 (C(2)), 128.97-130.33 (C(9, 10)) 173.09 (C(1))

EXAMPLE 4

N-isopentyloleamide

(11) According to the same procedure of Example 1, N-isopentyloleamide was prepared from oleoyl chloride and 3-methylbutan-1-amine in the presence of triethylamine in a yield of 54%.

(12) .sup.1H NMR (600 MHz, DMSO-d.sub.6) ppm 0.78-0.92 (m, 9H, CH(18, 22, 23) 1.14-1.34 (m, 22H, CH(4, 5, 6, 7, 12, 13, 14, 15, 16, 17, 20) 1.39-1.50 (m, 2H, HC(3)) 1.55 (sept, J=6.61 Hz, 1H, HC(21)) 1.91-2.06 (m, 6H, HC(2, 8, 11)) 2.98-3.07 (m, 2H, HC(19)) 5.31 (t, J=4.81 Hz, 2H, HC(9, 10)) 7.69 (t, J=5.33 Hz, 2H, HN)

(13) .sup.13C NMR (150 MHz, DMSO-d.sub.6) ppm 13.93 (C(18)), 22.09 (C(17)), 22.34 (C(22, 23)) 25.10 (C(3)), 26.50-26.63 (C(8, 11)), 28.48-29.13 (C(3, 4, 5, 6, 7, 12, 13, 14, 15, 21)) 31.29 (C(16)), 35.39 (C(2)), 36.53 (C(20)), 38.19 (C(19)), 129.59 (C(9, 10), 171.74 (C(1))

EXAMPLE 5

N-(2-hydroxyethyl)oleamide

(14) According to the same procedure of Example 1, N-(2-hydroxyethyl)oleamide was prepared from oleoyl chloride and 2-aminoethanol in the presence of triethylamine in a yield of 88%.

(15) .sup.1H NMR (600 MHz, DMSO-d.sub.6) ppm 0.85 (t, J=7.05 Hz, 3H, HC(18)) 1.16-1.35 (m, 20H, HC(4, 5, 6, 7, 12, 13, 14, 15, 16, 17)) 1.45 (quin, J=7.22 Hz, 2H, HC(3)) 1.97 (q, J=6.53 Hz, 4H, HC(8, 11)) 2.03 (t, J=7.39 Hz, 2H, HC(2)) 3.08 (q, J=5.84 Hz, 2H, HC(20)) 3.36 (t, J=6.01 Hz, 2H, HC(19)) 4.66 (br. s., 1H, OH) 5.24-5.38 (m, 2H, HC(9, 10)) 7.78 (t, J=4.98 Hz, 1H, HN)

(16) .sup.13C NMR (150 MHz, DMSO-d.sub.6) ppm 13.92 (C(18, 22.09 (C(17, 25.27 (C(3)), 26.53-26.78 (C(8, 11)), 28.06-29.71 (C(4, 5, 6, 7, 12, 13, 14, 15) 31.29 (C(16)), 35.34 (C(2)), 41.39 (C(20)), 59.97 (C(19)), 41.39 (C(20)), 129.59 (C(9, 10), 172.17 (C(1))

EXAMPLE 6

N-(4-amino-4-oxobutyl)oleamide

a) methyl 4-oleamidobutanoate

(17) In a 250 mL round-bottomed flask fitted with a stirrer, cooler and dropping funnel methyl 4-aminobutanoate, HCl (5 g, 32.6 mmol) was dissolved in a solution of triethylamine (5.44 ml, 39.1 mmol) in DCM (Volume: 100 ml). Oleoyl chloride (9.79 g, 32.6 mmol) was added dropwise and stirring was continued for 3 hours at room temperature.

(18) Mixture was diluted with DCM and water, acidified with a 37% aqueous solution of HCl (5.35 ml, 65.1 mmol) and extracted with ethylacetate.

(19) Organic layers were combined, dried and evaporated.

(20) Residue was purified by flash column chromatography, eluent DCM/methanol

(21) 4 g of light brown product was isolated, purity >95%, yield: 31%

b) N-(4-amino-4-oxobutyl)oleamide

(22) Methyl 4-oleamidobutanoate (2 g, 5.24 mmol) was dissolved in a commercially available ammonia solution in methanol. Solution stand over during the weekend. Volatiles were evaporated and 1.9 g of N-(4-amino-4-oxobutyl)oleamide was obtained.

(23) Purity: 95%, Yield: 99%

(24) .sup.1H NMR (600 MHz, DMSO-d.sub.6) ppm 0.83-0.87 (m, 2H, HC(18)) 1.18-1.32 (m, 20H, HC(4, 5, 6, 7, 12, 13, 14, 15, 16, 17) 1.46 (quin, J=7.30 Hz, 2H, HC(3)) 1.57 (quin, J=7.30 Hz, 2H, HC(21))) 1.95-2.00 (m, 4H, H_C(8, 11)) 2.02 (t, J=7.39 Hz, 4H, HC(2, 20)) 2.94-3.05 (m, 2H, HC(22)) 5.24-5.39 (m, 2H, HC(9, 10)) 7.75 (t, J=5.50 Hz, 1H, HN)

(25) .sup.13C NMR (150 MHz, DMSO-d.sub.6) ppm 13.94 (C(18)), 22.07 (C(17)), 25.23-25.31(C(3, 21), 26.51-26.62 (C(8, 11)), 28.47-29.14 (C(4, 5, 6, 7, 12, 13, 14, 15)), 31.26 (C(16)), 32.56 (C(20)), 35.41 (C(2), 38.11 (C(22)) 129.62 (C(9, 10) 171.94 (C(1)), 173.89 (C(19))

EXAMPLE 7

3-[(9Z)-octadec-9-enoylamino]propanoic Acid

(26) The first step was a reaction between methyl propanoate and oleoyl chloride similar to step 1 in example 6: yield 30%. The hydrolysis of the ester group was achieved by stirring the product of step 1 in a 5% aqueous NaOH in methanol (1/1) solution overnight at room temperature. After work up a yellow oil was obtained: yield 90%.

(27) .sup.1H NMR (600 MHz, DMSO-d.sub.6) ppm 0.85 (t, J=6.87 Hz, 3H, HC(18)) 1.16-1.33 (m, 20H, HC(4, 5, 6, 7, 12, 13, 14, 15, 16, 17) 1.45 (quin, J=7.22 Hz, 2H, HC(3))) 1.97 (q, J=6.07 Hz, 4H, HC(8, 11)) 2.01 (t, J=7.39 Hz, 2H, HC(2)) 2.34 (t, J=6.87 Hz, 2H, HC(20)) 3.21 (q, J=6.53 Hz, 2H, HC(21)) 5.26-5.38 (m, 2H, HC(9,10) 7.84 (t, J=5.33 Hz, 1H, HN))

(28) .sup.13C NMR (150 MHz, DMSO-d.sub.6) ppm 13.93 (C(18)), 22.10 (C(17)), 25.24 (C(3)), 26.50-26.67 (C(8, 11)) 28.43-29.20 (C(4, 5, 6, 7, 12, 13, 14, 15) 31.29 (C(16)) 33.95 (C(20)), 34.68 (C(21)), 35.27 (C(2)) 128.95-129.91 (C(9, 10)), 172.13 (C(1)), 172.89 (C(19))

EXAMPLE 8

N-(2-hydroxyethyl)linolenamide

(29) N-(2-hydroxyethyl)linolenamide was prepared according to example 5 from linoleoyl chloride and ethanolamine. After column chromatography a yield of 70% was obtained.

EXAMPLE 9

N-(2-hydroxyethyl)eicosanamide

(30) N-(2-hydroxyethyl)eicosanamide was prepared according to example 5 form eicosanoyl chloride and ethanolamine. After column chromatography a yield of 80% was obtained.

EXAMPLE 10

N-(2-hydroxyethyl)arachidonamide

(31) N-(2-hydroxyethyl)arachidonamide was prepared according to example 5 form arachidonoyl chloride and ethnolamine. After column chromatography a yield of 65% was obtained.

EXAMPLE 11

Beef Bouillon

(32) 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 N-(2-hydroxyethyl)linolenamide (Ex. 8) was added to the bouillon the panel agreed that the bouillon tasted more fatty, and slightly more salty than the reference. b) When 40 ppb of N-(2-hydroxyethyl)eicosanamide (Ex. 9) was added to the bouillon the panel agreed that the bouillon tasted more fatty, beefier and smoky, tasted more fully and had more body than the reference. c) When 40 ppb of N-(2-hydroxyethyl)arachidonamide (Ex. 10) was added to the bouillon the panel agreed that the bouillon tasted saltier, sweeter, more fatty and slightly more umami than the reference, and had more mouthfeel. d) When 0.5 ppm of N-(4-amino-4-oxobutyl)oleamide (Ex. 6) was dosed to the bouillon the panel agreed that this drink tasted more full and had more mouthfeel than the reference. e) When 0.5 ppm of N-(2-hydroxyethyl)arachidonamide (Ex 10) was dosed to the bouillon the panel agreed that this drink had more mouthfeel and tasted more salty and more umami than the reference.

EXAMPLE 12

Mango-Flavoured Beverage

(33) A mango-flavoured beverage was prepared using a standard mango flavour (0.05% w/w), mango juice (0.18% w/w), sugar (8% w/w) and citric acid (0.1% w/w). The drinks were evaluated by a panel of experienced tasters. a) When 0.5 ppm of N-(3-(methylthio)propyl)oleamide (Ex. 2) was dosed to the mango drink the panel agreed that the drink tasted more tropical and more juicy than the reference drink. b) When 0.5 ppm of N-isopentyloleamide (Example 4) was dosed to the mango drink the panel agreed that the drink tasted somewhat more astringent and fruity and had more body.