Dihydrocapsiate

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.54 g, 8.95 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and Novozym 435 (8.90 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 55° C. for 45 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (10 ml) was added to the reaction mixture, and the mixture was stirred for 30 minutes. Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained colorless oil (2.67 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 97.2 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with water (15 ml) and saturated brine (15 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.67 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 95.9%, and the purity was 99.4 area % by HPLC. The mixture contained 3.86 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 30 minutes Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with water (15 ml) and saturated brine (15 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.54 g, 8.95 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and Novozym 435 (67.0 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 55° C. for 16 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (5 ml) was added to the reaction mixture, and the mixture was stirred for 10 minutes. Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained colorless oil (2.74 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 96.0 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.65 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 97.6%, and the purity was 99.8 area % by HPLC. The mixture contained 1.12 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 10 minutes Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.54 g, 8.95 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and Novozym 435 (67.0 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 55° C. for 16 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (5 ml) was added to the reaction mixture, and the mixture was stirred for 10 minutes. Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained colorless oil (2.74 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 96.0 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.65 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 97.6%, and the purity was 99.8 area % by HPLC. The mixture contained 1.12 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 10 minutes Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.54 g, 8.95 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and lipase PS-C “Amano” I (enzyme immobilized on ceramic: 335 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 55° C. for 13.5 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (5 ml) was added to the reaction mixture, and the mixture was stirred for 15 minutes. The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained oil (2.73 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 96.3 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.67 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 95.5%, and the purity was 99.3 area % by HPLC. The mixture contained 4.18 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 15 minutes The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.54 g, 8.95 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and lipase PS-C “Amano” I (enzyme immobilized on ceramic: 335 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 55° C. for 13.5 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (5 ml) was added to the reaction mixture, and the mixture was stirred for 15 minutes. The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained oil (2.73 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 96.3 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.67 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 95.5%, and the purity was 99.3 area % by HPLC. The mixture contained 4.18 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 15 minutes The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.54 g, 8.95 mmol) and vanillyl alcohol (1.34 g, 8.70 mmol) were measured and placed in a flask (25 ml) and dissolved in heptane (0.5 ml). Lipase PS-C “Amano” I (enzyme immobilized on ceramic: 335 mg) was added and the mixture was heated with stirring in an oil bath at 55° C. for 13.5 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (5 ml) was added to the reaction mixture, and the mixture was stirred for 10 minutes. The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained oil (2.42 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 97.2 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.42 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 72.3%, and the purity was 99.6 area % by HPLC. The mixture contained 24.8 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask Lipase PS-C “Amano” I (enzyme immobilized on ceramic: 335 mg) was added the mixture was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 10 minutes The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with water (10 ml) and saturated brine (10 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.65 g, 9.59 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and lipase PS-C “Amano” I (enzyme immobilized on ceramic: 335 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 45° C. for 37.5 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (10 ml) was added to the reaction mixture, and the mixture was stirred for 10 minutes. The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained oil was analyzed by HPLC to find that dihydrocapsiate was contained in 95.7 area %. The mixture was partitioned with heptane (20 ml) and 10% aqueous citric acid solution (20 ml), and the aqueous layer was further extracted with heptane (20 ml). The combined heptane layer was washed with saturated brine (15 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.50 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 73.1%, and the purity was 99.3 area % by HPLC. The mixture contained 27.4 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 10 minutes The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (20 ml) and 10% aqueous citric acid solution (20 ml) the aqueous layer was further extracted with heptane (20 ml) The combined heptane layer was washed with saturated brine (15 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.65 g, 9.59 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and lipase PS-C “Amano” I (enzyme immobilized on ceramic: 335 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 45° C. for 37.5 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (10 ml) was added to the reaction mixture, and the mixture was stirred for 10 minutes. The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained oil was analyzed by HPLC to find that dihydrocapsiate was contained in 95.7 area %. The mixture was partitioned with heptane (20 ml) and 10% aqueous citric acid solution (20 ml), and the aqueous layer was further extracted with heptane (20 ml). The combined heptane layer was washed with saturated brine (15 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.50 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 73.1%, and the purity was 99.3 area % by HPLC. The mixture contained 27.4 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 10 minutes The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (20 ml) and 10% aqueous citric acid solution (20 ml) the aqueous layer was further extracted with heptane (20 ml) The combined heptane layer was washed with saturated brine (15 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.50 g, 8.70 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and lipase PS-C “Amano” I (enzyme immobilized on ceramic: 375 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 55° C. for 45 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (10 ml) was added to the reaction mixture, and the mixture was stirred for 10 minutes. The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained oil (2.68 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 92.9 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with saturated brine (15 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.61 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 95.5%, and the purity was 97.1 area % by HPLC. The mixture contained 1.97 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 10 minutes The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with saturated brine (15 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.50 g, 8.70 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and lipase PS “Amano” (375 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 55° C. for 45 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (10 ml) was added to the reaction mixture, and the mixture was stirred for 10 minutes. Lipase PS “Amano” and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure and the obtained oil (2.48 g) was analyzed by HPLC to find that dihydrocapsiate was contained in 94.0 area %. The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml), and the aqueous layer was further extracted with heptane (15 ml). The combined heptane layer was washed with saturated brine (15 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.45 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 80.9%, and the purity was 97.4 area % by HPLC. The mixture contained 12.6 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature the mixture was stirred for 10 minutes Lipase PS “Amano” and a small amount of precipitated vanillyl alcohol were removed by filtration The filtrate was concentrated under reduced pressure The mixture was partitioned with heptane (15 ml) and 10% aqueous citric acid solution (15 ml) the aqueous layer was further extracted with heptane (15 ml) The combined heptane layer was washed with saturated brine (15 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-Methylnonanoic acid (1.00 g, 5.80 mmol), vanillyl alcohol (851 mg, 5.52 mmol), and Novozym 435 (50 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 50° C. for 20 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The reaction mixture was returned to room temperature, hexane (25 ml) was added, and Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration. Hexane (25 ml) was added to the filtrate, and the mixture was washed with 5% aqueous citric acid solution (25 ml) and saturated brine (25 ml), and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (1.66 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 89.7%, and the purity was 99.5 area % by HPLC. The mixture contained 8.0 wt % of 8-methylnonanoic acid relative to dihydrocapsiate. placed in a flask The mixture in the flask free of a plug was heated After 2 to 3 hours of stirring with heating was returned to room temperature Novozym 435 and a small amount of precipitated vanillyl alcohol were removed by filtration Hexane (25 ml) was added to the filtrate the mixture was washed with 5% aqueous citric acid solution (25 ml) and saturated brine (25 ml) dried over anhydrous magnesium sulfate Magnesium sulfate was removed by filtration the filtrate was concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using vanillyl alcohol (1.70 g, 11.0 mmol) instead of homovanillyl alcohol, and n-decanoic acid (1.72 g, 10 mmol) instead of 8-methylnonanoic acid in Example 1, similar reaction was performed. The residue was purified by PTLC to find that the yield of the obtained vanillyl decanoate was 1.33 g (4.31 mmol, 43.1%), and vanillyl decanoate was decomposed (i.e., unstabilized) by the contact with silica gel. In contrast, the isolation yield of homovanillyl 8-methylnonanoate obtained by similar operation was 93.2% as mentioned above, suggesting that homovanillyl 8-methylnonanoate is far stabler than vanillyl decanoate even upon contact with silica gel. In addition, since good isolation yields were obtained in Examples 2 to 23 where isolation and purification were similarly performed by PTLC, it is clear that the compound of the present invention is superior to capsinoids in the stability. In addition, since good isolation yields were obtained in Examples 2 to 23 where isolation and purification