Production method of capsinoid by dehydrating condensation, stabilizing method of capsinoid, and capsinoid composition

Abstract

Capsinoids of formula (3) may be conveniently prepared in a high yield, in a short time, without using a dehydrating agent by esterification of a fatty acid of formula (1) with a hydroxymethylphenol of formula (2) using an enzyme without a solvent or in a low-polar solvent. Addition of a fatty acid represented by formula (4) is effective for stabilizing the ester compound of formula (3). wherein each symbol is as defined in the specification.

1 . A method of producing an ester compound represented by formula (3): 
     
       
         
         
             
             
         
       
     
     wherein
 R1 is an unsubstituted or substituted alkyl group having 5 to 25 carbon atoms or an unsubstituted or substituted alkenyl group having 5 to 25 carbon atoms, and 
 R2 to R6 are each independently a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 25 carbon atoms, an alkenyl group having 2 to 25 carbon atoms, an alkynyl group having 2 to 25 carbon atoms, an alkoxy group having 1 to 25 carbon atoms, an alkenyloxy group having 2 to 25 carbon atoms or an alkynyloxy group having 2 to 25 carbon atoms, wherein at least one of R2 to R6 is a hydroxyl group, 
 which method comprises: 
 (a) condensing a fatty acid represented by formula (1): 
 
     
       
         
         
             
             
         
       
       
         wherein R1 is as defined above, 
         and a hydroxymethylphenol represented by formula (2): 
       
     
     
       
         
         
             
             
         
       
       wherein R2 to R6 are as defined above, 
     
     said condensing occurring in the presence of an enzyme as a catalyst and without the presence of a solvent or within a low-polar solvent. 
   
   
       2 . The method of  claim 1 , wherein the low-polar solvent is at least one solvent selected from the group consisting of heptane; hexane; pentane; toluene; 4-methyl-2-pentanone; 2-butanone; 1,2-dimethoxyethane; and a mixture thereof. 
   
   
       3 . The method of  claim 1 , wherein said hydroxymethylphenol represented by formula (2) is vanillyl alcohol. 
   
   
       4 . The method of  claim 1 , wherein said fatty acid represented by formula (1) is present in a molar excess as compared to said hydroxymethylphenol represented by formula (2), such that an amount of said fatty acid represented by formula (1) is contained in the reaction mixture after said condensing. 
   
   
       5 . The method of  claim 1 , which further comprises:
 (b) adding a fatty acid represented by formula (4):   
     
       
         
         
             
             
         
       
     
     wherein
 R1′ is an unsubstituted or substituted alkyl group having 5 to 25 carbon atoms or an unsubstituted or substituted alkenyl group having 5 to 25 carbon atoms, 
 
     after said condensing of said fatty acid represented by formula (1) and said hydroxymethylphenol represented by formula (2). 
   
   
       6 . The method of  claim 4 , which further comprises:
 (b′) after said condensing, preparatively separating said ester compound represented by formula (3) as a mixture with said fatty acid represented by formula (1).   
   
   
       7 . The method of  claim 5 , which further comprises:
 (b′) after the condensation, preparatively separating said ester compound represented by formula (3) as a mixture with said fatty acid represented by formula (4).   
   
   
       8 . The method of  claim 1 , wherein R1 is a group selected from the group consisting of a hexyl group; a 5-methylhexyl group; a trans-5-methyl-3-hexenyl group; a heptyl group; a 6-methylheptyl group; a 5-methylheptyl group; a trans-6-methyl-4-heptenyl group; an octyl group; a 7-methyloctyl group; a trans-7-methyl-5-octenyl group; a nonyl group; a 8-methylnonyl group; a 7-methylnonyl group; a trans-8-methyl-6-nonenyl group; a trans-8-methyl-5-nonenyl group; a trans-7-methyl-5-nonenyl group; a decyl group; a 9-methyldecyl group; a trans-9-methyl-7-decenyl group; a trans-9-methyl-6-decenyl group; an undecyl group; and a dodecyl group. 
   
   
       9 . The method of  claim 1 , wherein said enzyme is lipase. 
   
   
       10 . The method of  claim 1 , wherein said condensing is carried out at a temperature of 15° C. to 90° C. 
   
   
       11 . The method of  claim 1 , wherein said fatty acid represented by formula (1) is obtained by a method comprising:
 (i) hydrolyzing an ester compound represented by formula (8):   
     
       
         
         
             
             
         
       
     
     wherein
 R1 is as defined above, and 
 Rc is a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, an allyl group, or a benzyl group; and 
 (ii) subjecting the resulting compound to (A) reacting the compound with a base to form a salt crystal and converting the crystal to a free form thereof, and/or (B) distillation. 
 
   
   
       12 . The method of  claim 11 , wherein said ester compound represented by formula (8) is obtained by a method comprising:
 (A) converting a compound represented by formula (5):
   Ra—X  (5) 
   
     wherein
 Ra is an unsubstituted or substituted alkyl group having 1 to 24 carbon atoms or an unsubstituted or substituted alkenyl group having 2 to 24 carbon atoms, and 
 X is a halogen atom, 
 
     to a Grignard reagent represented by the formula (6):
   Ra—MgX  (6) 
 wherein Ra and X are as defined above, and 
 (B) cross coupling said Grignard reagent with a compound represented by formula (7): 
 
     
       
         
         
             
             
         
       
     
     wherein
 Rb is an unsubstituted or substituted alkyl group having 1 to 24 carbon atoms or an unsubstituted or substituted alkenyl group having 2 to 24 carbon atoms, provided that the total of the carbon atoms of Ra and Rb is 5 to 25, 
 Rc is as defined above, and 
 Y is a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy group, or a trifluoromethanesulfonyloxy group. 
 
   
   
       13 . The method of  claim 1 , wherein said fatty acid represented by formula (1) is obtained by a method comprising:
 (i) reacting a mixture of a fatty acid represented by formula (10):   
     
       
         
         
             
             
         
       
     
     wherein
 Rd and Re are each independently a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, m is 0 or 1, and n is an integer of 1 to 5, 
 
     and a cis isomer thereof with a base to form salts thereof;
 (ii) purifying, based on the difference in the crystallinity or solubility of the formed salts, a salt of the fatty acid represented by formula (10); and 
 (iii) then converting said salt to a free form thereof. 
 
   
   
       14 . A method of making a food composition, comprising:
 (1) incorporating an ester compound represented by formula (3):   
     
       
         
         
             
             
         
       
     
     wherein
 R1 is an unsubstituted or substituted alkyl group having 5 to 25 carbon atoms or an unsubstituted or substituted alkenyl group having 5 to 25 carbon atoms, and 
 R2 to R6 are each independently a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 25 carbon atoms, an alkenyl group having 2 to 25 carbon atoms, an alkynyl group having 2 to 25 carbon atoms, an alkoxy group having 1 to 25 carbon atoms, an alkenyloxy group having 2 to 25 carbon atoms or an alkynyloxy group having 2 to 25 carbon atoms, wherein at least one of R2 to R6 is a hydroxyl group, into a food, 
 wherein said ester compound represented by formula (3) is prepared by a method according to  claim 1 . 
 
   
   
       15 . A method of making a nutraceutical composition, comprising:
 (1) incorporating an ester compound represented by formula (3):   
     
       
         
         
             
             
         
       
     
     wherein
 R1 is an unsubstituted or substituted alkyl group having 5 to 25 carbon atoms or an unsubstituted or substituted alkenyl group having 5 to 25 carbon atoms, and 
 R2 to R6 are each independently a hydrogen atom, a hydroxyl group, an alkyl group having 1 to 25 carbon atoms, an alkenyl group having 2 to 25 carbon atoms, an alkynyl group having 2 to 25 carbon atoms, an alkoxy group having 1 to 25 carbon atoms, an alkenyloxy group having 2 to 25 carbon atoms or an alkynyloxy group having 2 to 25 carbon atoms, wherein at least one of R2 to R6 is a hydroxyl group, into a nutraceutical, 
 wherein said ester compound represented by formula (3) is prepared by a method according to  claim 1 .