Novel intermediate for sweetener with high sweetness and process for producing the same

Abstract

The present invention relates to a 3-substituted-phenyl-3-merthylbutyric acid and 3-substituted-phenyl-3-merthylaldehyde derivatives, which are useful in the production of N-[N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, which is a sweetener with high sweetening potency.

1 . A process for producing a compound of formula (2), which comprises: 
 reacting a compound of formula (1) with 3-methylcrotonic acid in the presence of an acid,                          wherein R is a sulfonyl-type-protecting group, and Me is a methyl group.    
     
     
         2 . The process as defined in  claim 1 , wherein the sulfonyl-type protecting group is represented by the formula: —SO 2 —R′, wherein 
 R′ is selected from the group consisting of an unsubstituted straight chain alkyl group having 1 to 10 carbon atoms; an unsubstituted branched chain alkyl group having 1 to 10 carbon atoms, a substituted straight chain alkyl group having 1 to 10 carbon atoms; a substituted branched chain alkyl group having 1 to 10 carbon atoms; an unsubstituted aryl group having 6 to 15 carbon atoms, a substituted aryl group having 6 to 15 carbon atoms; an unsubstituted aralkyl group having 7 to 20 carbon atoms; and a substituted aralkyl group having 7 to 20 carbon atom.  
 
     
     
         3 . The process as defined in  claim 2 , wherein said alkyl group is fluorinated.  
     
     
         4 . The process as defined in  claim 2 , wherein said aralkyl group is fluorinated.  
     
     
         5 . The process as defined in  claim 1 , wherein said sulfonyl-type protecting is selected from the group consisting of a benzene sulfonyl group, a p-toluene sulfonyl group, a p-bromobenzene sulfonyl group, a p-nitrobenzene sulfonyl group, a methane sulfonyl group, an ammonioalkane sulfonyl group, a trifluoromethane sulfonyl group, a nonafluorobuthane sulfonyl group, and a 2,2,2-trifluoroethane sulfonyl group.  
     
     
         6 . The process as defined in  claim 1 , wherein said sulfonyl-type protecting group is selected from the group consisting of a methane sulfonyl group, a trifluoromethane sulfonyl group, and a p-toluene sulfonyl group.  
     
     
         7 . The process as defined in  claim 1 , wherein said sulfonyl type protecting group is a methane sulfonyl group.  
     
     
         8 . A process for producing 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyric acid, which comprises: 
 converting the substituent at the 3-position in the phenyl group of the compound of formula (2) obtained by the process as defined in  claim 1  to a hydroxyl group.    
     
     
         9 . The process as defined in  claim 8 , wherein said converting the substituent at the 3-position comprises sulfonic acid ester hydrolysis.  
     
     
         10 . A process for producing a 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl aldehyde, which comprises: 
 converting a carboxyl group in the 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyric acid obtained by the process defined in  claim 8 , into a formyl group.    
     
     
         11 . A process for producing a 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl aldehyde, which comprises: 
 converting a carboxyl group in the 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyric acid obtained by the process defined in  claim 9 , into a formyl group.    
     
     
         12 . A process for producing a 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl aldehyde, which comprises: 
 converting the 3-substituted-phenyl-3-methylbutyric acid obtained by the process as defined in  claim 1  to a hydroxyl group; and converting the carboxyl group thereof into a formyl group.    
     
     
         13 . The process as defined in  claim 12 , wherein said converting the substituent at the 3-position comprises sulfonic acid ester hydrolysis.  
     
     
         14 . A process for producing a N-[N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, which comprises: 
 reductively alkylating the 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl aldehyde obtained by he process as defined in  claim 10  with aspartame.  
 
     
     
         15 . A process for producing a N-[N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, which comprises: 
 reductively alkylating the 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl aldehyde obtained by he process as defined in  claim 11  with aspartame.  
 
     
     
         16 . A process for producing a N-[N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-L-α-aspartyl]-L-phenylalanine 1-methyl ester, which comprises: 
 reductively alkylating the 3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl aldehyde obtained by he process as defined in  claim 12  with aspartame.  
 
     
     
         17 . A compound of formula (3):  
       
         
           
           
               
               
           
         
         wherein R is a sulfonyl type protecting group; Me is a methyl group; and R 1  is a carboxyl group, a formyl group or a hydroxymethyl group.  
       
     
     
         18 . The compound as defined in  claim 17 , wherein R is a protecting group represented by the formula: —SO 2 —R′, 
 R′ is selected from the group consisting of an unsubstituted straight chain alkyl group having 1 to 10 carbon atoms; an unsubstituted branched chain alkyl group having 1 to 10 carbon atoms, a substituted straight chain alkyl group having 1 to 10 carbon atoms; a substituted branched chain alkyl group having 1 to 10 carbon atoms; an unsubstituted aryl group having 6 to 15 carbon atoms, a substituted aryl group having 6 to 15 carbon atoms; an unsubstituted aralkyl group having 7 to 20 carbon atoms; and a substituted aralkyl group having 7 to 20 carbon atom.  
 
     
     
         19 . The compound as defined in  claim 17 , wherein said alkyl group is fluorinated.  
     
     
         20  The compound as defined in  claim 17 , wherein said aralkyl group is fluorinated.  
     
     
         21 . The compound as defined in  claim 17 , wherein 
 R 1  is a carboxyl group, and    R is selected from the group consisting of a benzene sulfonyl group, a p-toluene sulfonyl group, a p-bromobenzene sulfonyl group, a p-nitrobenzene sulfonyl group, a methane sulfonyl group, an ammonioalkane sulfonyl group, a trifluoromethane sulfonyl group, a nonafluorobuthane sulfonyl group, and a 2,2,2-trifluoroethane sulfonyl group    
     
     
         22 . The compound as defined in  claim 17 , wherein 
 R 1  is a carboxyl group, and    R is selected from the group consisting of a methane sulfonyl group, a trifluoromethane sulfonyl group, and a p-toluene sulfonyl group.    
     
     
         23 . The compound as defined in  claim 17 , wherein R 1  is a carboxyl group, and R is a methane sulfonyl group.  
     
     
         24 . 3-(3-methanesulfonyloxy-4-methoxyphenyl)-3-methylbutyric acid.