Nitrons Carrying a Positive Charge and Usable in Trapping Free Radicals, Especially the Superoxide Radical

Abstract

The present invention involves new nitrons carrying a positive charge, useful in trapping of free radicals and especially the superoxide radical, of general formula:

1 . A method for preparing a compound derived from cyclical nitrons of the general formula 
     
       
         
         
             
             
         
       
       in which R1 represents a phenyl, a (C1-C18) aryl or a (C1-C18) alkyl, 
       R2 represents an atom of hydrogen, of deuterium, a phenyl group, a (C1-C18) aryl, (C1-C18) alkyl, or a radical Z1 of formula 
     
     
       
         
         
             
             
         
       
       in which A1 is a single bond, a methylene group, or an oxymethylene group (where the oxygen atom is bound to the phosphorus atom of the radical Z1), X represents an atom of oxygen or of sulfur, Y represents an atom of oxygen and R represents an atom of hydrogen, a (C1-C18) alkyl or a (C6-C18) aryl or Y represents a methylene group and R represents an atom of hydrogen, a (C1-C17) alkyl or (C6-C18) aryl, 
       or a radical Z3 of formula 
     
     
       
         
         
             
             
         
       
       in which R represents an atom of hydrogen, a (C1-C17) alkyl or a (C6-C18) aryl group 
       R3 and R5 represent, independently, an atom of hydrogen, of deuterium, a phenyl, (C1-C18) aryl, or (C1-C18) alkyl group, 
       R4 represents a radical of formula 
     
     
       
         
         
             
             
         
       
       in which X is a (C1-C18) alkyl or (C6-C18) aryl, 
       A2 is an atom of oxygen, of nitrogen, or of carbon and Z is a positively charged group, such as triaryl phosphonium —P + (Ar) 3 , Ar being a (C6-C18) aryl group, guanidinium —NH—C(=NH)NH 3   + , ammonium —N + (R) 3 , sulfonium S + (R) 2 , in which R is a group chosen from among the (C1-C18) alkyl and (C6-C18) aryl groups, substituted or not, saturated or not, possibly containing at least one atom of oxygen, nitrogen, and sulfur, 
       R6 is an atom of-hydrogen, of deuterium, a phenyl, (C1-C18) aryl, (C1-C18) alkyl group, or a radical Z2 of formula 
     
     
       
         
         
             
             
         
       
       in which A2 is a single bond, a methylene group, or an oxymethylene group (where the oxygen atom is bound to the phosphorus atom of the radical Z2), X represents an atom of oxygen or of sulfur, Y represents an atom of oxygen and R represents an atom of hydrogen, a (C1-C18) alkyl or a (C6-C18) aryl, or Y represents a methylene group and R represents an atom of hydrogen, a (C1-C17) alkyl or (C6-C18) aryl, and 
       R7 represents an atom of hydrogen, of deuterium, or a methyl group, said method comprises synthesizing 4HMDEPMPO. 
     
   
   
       2 . The method of  claim 1 , said compound further comprises; 
     
       
         
         
             
             
         
       
       in which X is a (C1-C18) alkyl or (C6-C18) aryl, 
       A2 is an atom of oxygen, of nitrogen or of carbon and Z is a positively charged group, such as triaryl phosphonium —P + (Ar) 3 , guanidinium —NH—C(=NH)NH 3   + , ammonium —N + (R) 3 , sulfonium S + (R) 2 , in which R is a group chosen from among the (C1-C18) alkyl and (C6-C18) aryl groups, substituted or not, saturated or not, possibly containing at least one atom of oxygen, nitrogen, and sulfur. 
     
   
   
       3 . The method of  claim 2 , said compound further comprises; 
     
       
         
         
             
             
         
       
     
   
   
       4 . A method for preparing a trap compound of the following formula: 
     
       
         
         
             
             
         
       
       in which R1 represents a phenyl, a (C1-C18) aryl or a (C1-C18) alkyl, 
       R2 represents an atom of hydrogen, of deuterium, a phenyl group, a (C1-C18) aryl, (C1-C18) alkyl, or a radical Z1 of formula 
     
     
       
         
         
             
             
         
       
       in which A1 is a single bond, a methylene group, or an oxymethylene group (where the oxygen atom is bound to the phosphorus atom of the radical Z1), X represents an atom of oxygen or of sulfur, Y represents an atom of oxygen and R represents an atom of hydrogen, a (C1-C18) alkyl or a (C6-C18) aryl or Y represents a methylene group and R represents an atom of hydrogen, a (C1-C17) alkyl or (C6-C18) aryl, 
       R3 and R5 represent, independently, an atom of hydrogen, of deuterium, a phenyl, (C1-C18) aryl, or (C1-C18) alkyl group, 
       R4 represents a radical of formula 
     
     
       
         
         
             
             
         
       
       R6 is an atom of hydrogen, of deuterium, a phenyl, (C1-C18) aryl, (C1-C18) alkyl group, or a radical Z2 of formula 
     
     
       
         
         
             
             
         
       
       in which A2 is a single bond, a methylene group, or an oxymethylene group (where the oxygen atom is bound to the phosphorus atom of the radical Z2), X represents an atom of oxygen or of sulfur, Y represents an atom of oxygen and R represents an atom of hydrogen, a (C1-C18) alkyl or a (C6-C18) aryl, or Y represents a methylene group and R represents an atom of hydrogen, a (C1-C17) alkyl or (C6-C18) aryl, and 
       R7 represents an atom of hydrogen, of deuterium, or a methyl group. 
     
   
   
       5 . The method of  claim 4 , said trap compound further comprises compounds of the formula: 
     
       
         
         
             
             
         
       
     
   
   
       6 . A method for preparing the free radical trap compound of the formula 
     
       
         
         
             
             
         
       
       comprising the synthesis of 4HMDEPMPO by the following synthesis pathway: 
     
     
       
         
         
             
             
         
       
       followed by the carbonation of the nitron 5-diethoxyphosphoryl-5-methyl-4-hydroxymethyl-1-pyrroline N-oxide (4HMDEPMPO) thus obtained in solution in acetonitrile with succinimide carbonate and triethylamine 
     
     
       
         
         
             
             
         
       
       the nitron thus formed (SCMDEPMPO) being then caused to react with 1 equivalent of (2-aminoethyl) triphenyl phosphonium bromide in presence of triethylamine in dichlormethane, thereby producing the Mito-DEPMPO compound