Method for releasing a product comprising chemical oxidation, method for detecting said product and uses thereof

Abstract

This invention has as its object a method for releasing a product by subjecting a compound of Formula (II′): R′ 7 R′ 8 (HX)C 1 -C 2 (YH)R′ 9 R′ 10 to a chemical oxidation that cleaves the bond C 1 -C 2 to obtain the product. In the compound of Formula (II′): R′ 7 to R′ 10 , which are identical or different, correspond to a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted functional group; X and Y, which are identical or different, are an oxygen atom, a sulfur atom, or an amine of Formula -NR 11 R 12 , wherein R 11 is a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, and R 12 is not a hydrogen atom. The invention also has as its object a method for releasing a product that comprises, before the chemical oxidation stage, a first step for preparing the compound of Formula (II′). The released product can be a volatile molecule or an active substance or else a specific product. The invention also relates to a method for detecting the released product as well as its applications, in particular for detecting catalytic or enzymatic activities.

What is claimed is:  
     
         1 . A method for releasing a product, comprising subjecting a compound of Formula (II′):  
       
         
           
           
               
               
           
         
       
       to a chemical oxidation that cleaves the bond C1-C2 to obtain a released product, wherein in the compound of Formula (II′): 
 R′ 7  to R′ 10 , which are identical or different, correspond to a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted functional group,  
 X and Y, which are identical or different, are an oxygen atom, a sulfur atom, or an amine of Formula -NR 11 R 12 ; R 11  is a hydrogen atom, an alkyl group, or an optionally substituted aryl group, and R 12  is not a hydrogen atom.  
 
     
     
         2 . The method of release according to  claim 1 , wherein the released product corresponds to Formula  
       R′ 7 R′ 8 C 1 =X and/or R′ 9 R′ 10 C 2 =Y,  
       in which R′ 7  to R′ 10 , X, and Y have the same meanings as above.  
     
     
         3 . The method of release according to  claim 1 , wherein the released product corresponds to the product of at least one secondary reaction that is carried out on at least one compound of Formula  
       R′ 7 R′ 8 C 1 =X or R′ 9 R′ 10 C 2 =Y  
       in which R′ 7  to R′ 10 , X, and Y have the same meanings as above.  
     
     
         4 . The method according to  claim 1 , wherein said released product comprises a volatile molecule, an active substance, or a specific compound.  
     
     
         5 . The method according to  claim 1 , comprising carrying out said chemical oxidation reaction with an oxidizing chemical agent.  
     
     
         6 . The method according to  claim 1 , wherein the oxidizing chemical agent is H 5 I 6 , RuO 2 , OSO 4 , (CH 3 CH 2 CH 2 ) 4 N(RuO 4 ), NaClO 4 , NaIO 4 , Na 3 H 2 IO 6 , NaMnO 4 , K 2 OsO 4 , KIO 4 , KMnO 4 , KRuO 4 , K 2 RuO 4 , LiOCl, lead acetate, tetrapropyl ammonium periodate, chromic acid or salts of the latter, NaBiO 3 , Ph 3 BiCO 3 , Ca(OCl) 2 , reagents of Ce(IV), Cr(VI), salts of Co (II), IOAc, I(OAc) 3 , N-iodosuccinimide, VO(OAc), Pb(OAc) 4 , MnO 2 , H 2 O 2 , or a mixture of reagents H 2 O 2 , Na 2 WO 4 , and H 3 PO 4 .  
     
     
         7 . The method according to  claim 5 , wherein the oxidizing chemical agent is a periodate salt.  
     
     
         8 . The method according to  claim 1 , further comprising the step of preliminarily preparing the compound of Formula (II′).  
     
     
         9 . The method according to  claim 8 , wherein the step of preparing the compound of Formula (II′) comprises synthesizing of a reduced form of the ketone or aldehyde group of at least one product of Formula  
       R′ 9 R′ 10 C=Y and R′ 7 R′ 8 C 1 =X  
       in which R′ 7 , R′ 8 , R′ 9 , R′ 10 , X and Y have the same meanings as above.  
     
     
         10 . The method according to  claim 8 , wherein the compound of Formula (II′) is a compound of Formula (II)  
       
         
           
           
               
               
           
         
       
       in which, 
 X and Y, which are identical or different, are an oxygen atom, a sulfur atom, or an amine of Formula -NR 11 R 12 , and R 11  is a hydrogen atom, an alkyl group, or an optionally substituted aryl group and R 12  is not a hydrogen atom.  
 R 7  to R 10 , which are identical or different, are a hydrogen atom, an optionally substituted alkyl group, or an optionally substituted functional group, and at least one of groups R 7  to R 10  is a group Di, which is insensitive to [the stage (b)?] oxidation reaction and which has properties that can be detected after the cleavage of the bond C 1 -C 2.    
 
     
     
         11 . The method according to  claim 10 , comprising a first chemical transformation of a substrate to obtain a compound of Formula (II) then a chemical oxidation of said compound of Formula (II) to directly or indirectly obtain a detectable product.  
     
     
         12 . The method according to claims  10  or  11 , comprising: 
 a) carrying out a chemical transformation of a substrate of Formula (I) in which the bond C1-C2 is insensitive to a cleavage by a chemical oxidation reaction:  
                     
 into a compound of Formula (II) in which the bond C1-C2 is sensitive to a cleavage by a chemical oxidation reaction:  
                     
 and  
 (b) carrying out a chemical oxidation of the compound of Formula (II) that is obtained in stage (a) that cleaves the bond C1-C2 to directly or indirectly obtain a detectable product,  
 and wherein in the compounds of Formulas (I) and (II): 
 at least one of groups R 1  to R 6  is a group Di as defined in  claim 10 ,  
 groups R 1  to R 6 , which are identical or different, are a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted functional group, and in the case of a functional group of Formulas —OR12, —SR12, and -NR  11 R 12 , R 11  is a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, and R 12  is not a hydrogen atom,  
 group or groups R 1  to R 6  that after stage (a) form the groups of Formulas -XH and -YH are insensitive to stage (b) oxidation, or may be sensitive to this oxidation if the compound of corresponding Formula (I) does not produce the compound of Formula (II) during an oxidation of the type of that of stage (b),  
 X and Y, which are identical or different, are an oxygen atom, a sulfur atom, or an amine of Formula -NR 11 R 12 , and R 11  is a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, and R 12  is not a hydrogen atom,  
 R 7  to R 10 , which are identical or different, are either identical to at most four of groups R 1  to R 6 , or, because of the transformation of one or more of groups R 1  to R 6 , during the reaction of stage (a), are a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted functional group, and at least one of groups R7 to R10 is a group Di as defined in  claim 10 .  
 
 
     
     
         13 . The method according to  claim 8 , comprising the following stages: 
 (a) transforming a substrate of Formula (I′) in which the bond C 1 -C 2  is insensitive to a cleavage by a chemical oxidation reaction:                          into a compound of Formula (II′) in which the bond C 1 -C 2  is sensitive to a cleavage by a chemical oxidation reaction:                          and,    (b) the chemical oxidation of the compound of Formula (II′) that is obtained in stage (a) in the presence of a compound of Formula II, which cleaves the bond C 1 -C 2  to obtain at least one detectable product directly or indirectly,    wherein in the compound of Formula (I′): 
 groups R′ 1  to R′ 6 , which are identical or different, are a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted functional group, and in the case of a functional group of Formulas —OR 12 , —SR 12 , and -NR 11 R 12 , R 11  is a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, and R 12  is not a hydrogen atom,  
 group or groups R′ 1  to R′ 6  that after stage (a) form the groups of Formulas -XH and -YH are insensitive to stage (b) oxidation, or may be sensitive to this oxidation if the corresponding compound of Formula (I′) does not produce the compound of Formula (II′) during an oxidation of the type of that of stage (b),  
   wherein in the compound of Formula (II): 
 R 7  to R 10 , which are identical or different, correspond to a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted functional group, and at least one of groups R 7  to R 10  is group Di as defined in  claim 10 ,  
 X and Y, which are identical or different, are an oxygen atom, a sulfur atom, an amine of Formula -NR 11 R 12 , and R 11  is a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, and R 12  is not a hydrogen atom,  
   wherein in the compound of Formula (II′): 
 X and Y, which are identical or different, are an oxygen atom, a sulfur atom, or an amine of Formula -NR 11 R 12 , and R 11  is a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, and R 12  is not a hydrogen atom,  
 R′ 7  to R′ 10 , which are identical or different, are either identical to at most four of groups R 1  to R 6 , or, because of the transformation of one or more of groups R 1  to R 6 , during the reaction of stage (a), are a hydrogen atom, a substituted or unsubstituted alkyl group or a substituted or unsubstituted functional group.  
   
     
     
         14 . The method according to  claim 12 , wherein R 1  to R 6  or R′ 1  to R′ 6  are such that the bond C 1 -C 2  is part of at least one cycle.  
     
     
         15 . The method according to  claim 12 , wherein at least one pair of groups R 1  to R 6  or R′ 1  to R′ 6  together form an oxygen atom, a sulfur atom, or a group of Formula -NR 11 R 12 , and R 11  is a hydrogen atom, an alkyl group, or a substituted or unsubstituted aryl group, and R 12  is not a hydrogen atom.  
     
     
         16 . The method according to  claim 12 , wherein at most one pair of groups R 1  to R 6 , from which one is R 1 , R 2  or R 6  or R′ 1 , R′ 2  and R′ 6  respectively, and the other is R 3 , R 4  or R 5  or R′ 3 , R′ 4  and R′ 5  respectively, form a double bond between carbons C 1  and C 2 .  
     
     
         17 . The method according to  claim 12 , wherein at most two pairs of groups R 1  to R 6  or R′ 1  to R′ 6  respectively, from which one is R 1 , R 2  or R 6  or R′ 1 , R′ 2  or R′ 6  respectively, and the other is R 3 , R 4  or R 5  or R′ 3 , R′ 4  or R′ 5  respectively, form a triple bond.  
     
     
         18 . The method according to  claim 12 , wherein groups R 1  to R 6  or R′ 1  to R′ 6  are sensitive or insensitive to stage (b) oxidation and wherein stages (a) and (b) are not simultaneous.  
     
     
         19 . The method according to  claim 12 , wherein group or groups R 1  to R 6  or R′ 1  to R′ 6  are insensitive to stage (b) oxidation and wherein stages (a) and (b) are simultaneous.  
     
     
         20 . The method according to  claim 12 , wherein the chemical transformation is a catalytic reaction.  
     
     
         21 . The method according to  claim 20 , wherein the chemical transformation is an enzymatic reaction.  
     
     
         22 . The method according to  claim 12 , wherein groups R 1  to R 10  or R′ 1  to R′ 10  are stable in a reaction medium comprising an aqueous medium, an organic medium or a two-phase medium or a solid medium.  
     
     
         23 . The method according to  claim 12 , wherein one or the other or both stages (a) and (b) of the method of the invention are carried out in a reaction medium comprising an aqueous medium, an organic medium, a two-phase medium or a solid medium.  
     
     
         24 . The method according to  claim 12 , wherein the substrate that is used in the process of the invention comprises one or more chiral centers.  
     
     
         25 . The method according to  claim 12 , wherein the substrate corresponds to Formula (V) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 Di, R 1 , R 2 , R 3 , X and Y have the same meaning as in  claim 12 , and  
 at most one of groups P 1  and P 2  is a hydrogen atom, or P 1  and P 2 , which are identical or different, are an acyl group that is substituted by an aryl or alkyl or peptidyl group, a phosphate group, a phosphate ester group, a phosphonate group, a carbamyl group that is substituted by an aryl or acyl or peptidyl group, a glycosyl group or a sulfate group.  
 
     
     
         26 . The method according to  claim 12 , wherein the substrate corresponds to Formula (VI) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 Di R 1 , R 2 , R 3 , X and Y have the same meaning as in  claim 12 , and  
 P 3  is a carbonyl group, a group —PO 2 R 11  or a group —OR 11 PO—, where R 11  has the same meaning as in  claim 12 , a group —SO 2 , a group —CHOR 13  where R 13  represents an aryl, alkyl or glycosyl group, a group SiR 14 R 15  where R 14  and R 15 , which are identical or different, represent an aryl, alkyl, aryloxy or alkoxy group, and a group ASO 2 H—.  
 
     
     
         27 . The method according to  claim 12 , wherein the substrate corresponds to Formula (VII) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 Di, R 1 , R 2  and R 3  have the same meaning as in  claim 12 , and  
 G represents an oxygen atom, a sulfur atom or an amine group of Formula NR 11 R 12  where R 11  and R 12  have the same meaning as in  claim 12 .  
 
     
     
         28 . The method according to  claim 12 , wherein the substrate corresponds to Formula (VIII) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 Di, R 1 , R 2  and R 3 , have the same meanings as in  claim 12 .  
 
     
     
         29 . The method according to  claim 12 , wherein the substrate corresponds to Formula (IX) below:  
       
         
           
           
               
               
           
         
       
       in which Di, R 1 , R 3 , X and Y have the same meaning as in  claim 12 .  
     
     
         30 . The method according to  claim 12 , wherein the product that is obtained from the transformation of stage (a) of the substrate corresponds to Formula (X) below:  
       
         
           
           
               
               
           
         
       
       in which Di, R 8 , R 9 , R 10 , X and Y have the same meaning as in  claim 12 .  
     
     
         31 . The method according to  claim 12 , wherein the product that is obtained from the transformation of stage (a) corresponds to Formula (XV) below:  
       
         
           
           
               
               
           
         
       
       in which X, Y and Di have the same meaning as in  claim 12  and in which the chain that carries Di is attached to any of positions 1, 2 or 3 of the glycerol-containing derivative.  
     
     
         32 . The method according to  claim 1 , wherein the oxidation reaction is carried out in an organic medium.  
     
     
         33 . The method according to  claim 12 , wherein the chemical oxidation of the compound of Formula (II) produces the directly detectable product of Formula (XI) below:  
       
         
           
           
               
               
           
         
       
       in which Di, R 9  and Y have the same meanings as above.  
     
     
         34 . The method according to  claim 33 , wherein the product of Formula (XI) is a group that comprises an aromatic ketone, an aldehyde or a pheromone.  
     
     
         35 . The method according to  claim 12 , wherein the chemical oxidation of the compound of Formula (II) is followed by a beta-elimination reaction and produces the detectable product of Formula ZH.  
     
     
         36 . The method according to  claim 30  or  35 , wherein group Di of the product of Formula (II) or Formula (X) corresponds to Formula (XIII) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 R 16 , R 17  and R 18 , which are identical or different, represent a hydrogen atom, a substituted or unsubstituted alkyl group or a substituted or unsubstituted functional group,  
 Z is a precursor of a detectable product ZH.  
 
     
     
         37 . The method according to  claim 36 , wherein detectable product ZH is a derivative of an aromatic alcohol, a heteroaromatic alcohol, a heteroaromatic amine, a halogen atom or a phosphoric ester.  
     
     
         38 . The method according to  claim 37 , wherein ZH is fluorescein, phenolphthalein, phenol red, p-nitrophenol, o-nitrophenol, 2,4-dinitrophenol, 6-hydroxynaphthoic acid, 8-hydroxy-pyrene 1,3,6-trisulfonic acid, tyrosine, luciferin, 5-bromo-4-chloro-indolyl, indolyl, quinolinium, nitro-anilinium or pyridoxamine.  
     
     
         39 . The method according to  claim 12 , wherein: 
 the compound that is obtained from the transformation of the substrate after stage (a) corresponds to Formula (XIV) below:                          in which Di, R 8 , R 9 , X and Y have the same meaning as above,    it comprises a pair of detectable groups Di, which are identical or different, one attached to carbon C 1 , the second attached to carbon C 2 , and    the two detectable groups interact with one another.    
     
     
         40 . The method according to  claim 12 , wherein the degree of specificity of the substrate is provided by the structure of group or groups R 1  to R 6  of Formula (I) or R′ 1  to R′ 6  of Formula (I′).  
     
     
         41 . The method for detecting a chemical transformation of a substrate, comprising subjecting said substrate to a release method according to  claim 11 , and detecting the released product.  
     
     
         42 . A substrate capable of being used in the method according to  claim 12 , corresponding to Formula (V) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 Di, R 1 , R 2 , R 3 , X and Y have the same meaning as in  claim 12 , and  
 at most one of groups P 1  and P 2  is a hydrogen atom or P 1 , P 2 , which are identical or different, are an acyl group that is substituted by an aryl or alkyl or peptidyl group, a phosphate group, a phosphate ester group, a phosphonate group, a carbamyl group that is substituted by an aryl or alkyl or peptidyl group, a glycosyl group or a sulfate group.  
 
     
     
         43 . A substrate that is capable of being used in the method according to  claim 12 , that corresponds to Formula (VI) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 Di R 1 , R 2 , R 3 , X and Y have the same meaning as in  claim 12 , and  
 P 3  is a carbonyl group, a group —PO 2 R 11  or a group R 11 PO—, where R 1  has the same meaning as in  claim 12 , a group —SO 2 , a group —CHOR 13  where R 13  represents an aryl, alkyl or glycosyl group, a group SiR 14 R 15  where R 14  and R 15 , which are identical or different, represent an aryl, alkyl, aryloxy or alkoxy group and a group AsO 2 H—.  
 
     
     
         44 . A substrate that is capable of being used in the method according to  claim 12 , that corresponds to Formula (VII) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 Di, R 1 , R 2  and R 3  have the same meaning as in  claim 12 , and  
 G represents an oxygen atom, a sulfur atom or an amine group of Formula NR 11 R 12  where R 11 R 12  have the same meaning as in  claim 12 .  
 
     
     
         45 . A substrate that is capable of being used in the method according to  claim 12 , that corresponds to Formula (VIII) below:  
       
         
           
           
               
               
           
         
       
       in which: 
 Di, R 1 , R 2  and R 3  have the same meaning as in  claim 12 .  
 
     
     
         46 . A substrate that is capable of being used in a method according to  claim 12 , that corresponds to Formula (IX) below:  
       
         
           
           
               
               
           
         
       
       in which, 
 Di, R 1 , R 3 , X and Y have the same meaning as in  claim 12 .  
 
     
     
         47 . A substrate according to  claim 42 , wherein groups R1 to R3 are stable in a reaction medium.  
     
     
         48 . The substrate according to  claim 47 , wherein said reaction medium is an aqueous, organic, two-phase or solid medium.  
     
     
         49 . A chemical composition that comprises at least one compound of Formula (II′).  
     
     
         50 . The composition according to  claim 49 , further comprising an oxidizing agent.  
     
     
         51 . A method for the identification of a new catalyst or new activity of catalysts that are known to be able to transform a substrate of Formula (I) or of Formula (I′) respectively into a compound of Formula (II) or Formula (II′) comprising detecting a chemical transformation according to  claim 41 .  
     
     
         52 . A method for detecting said substrate of Formula (I) or of Formula (I′) that is produced during a chemical reaction comprising detecting a chemical transformation according to  claim 41 .  
     
     
         53 . The method according to  claim 51 , wherein the catalyst is contained in a biological sample and wherein a substrate of Formula (I) or Formula (I′) is added to said sample.  
     
     
         54 . A catalyst that can transform a substrate of Formula (I) or Formula (I′) respectively into a compound of Formula (II) or Formula (II′), whereby said transformation can be detected by a method according to  claim 41 .  
     
     
         55 . An enzyme that is able to transform a substrate of Formula (I) or Formula (I′) respectively into a compound of Formula (II) or Formula (II′), whereby said transformation can be detected by a method according to  claim 41.