Process for the preparation of oxidized phospholipids

A method of preparing a compound having a glycerolic backbone and at least one oxidized moiety-containing residue attached to the glycerolic backbone via an ether bond having Formula II:

• wherein:
• A1 is selected from the group consisting of CH2, CH═CH and C═O;
• A2 is CH2;
• R1 is an alkyl having 1-30 carbon atoms;
• R2 is
• whereas:
• X is an alkyl chain having 1-24 carbon atoms;
• Y is selected from the group consisting of hydrogen, hydroxy, alkyl, alkoxy, halide, acetoxy and an aromatic functional group;
• and
• Z is
• and
• R3 is hydrogen, alkyl, aryl, or a phosphorus containing moiety selected from the group consisting of phosphoric acid, phosphoryl choline, phosphoryl ethanolamine, phosphoryl serine, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl cardiolipin, phosphatidyl inositol, phosphoryl cardiolipin, phosphoryl inositol, ethylphosphocholine, phosphorylmethanol, phosphorylethanol, phosphorylpropanol, phosphorylbutanol, phosphorylethanolamine-N-lactose, phosphoethanolamine-N-[methoxy(propylene glycol)], phosphoinositol-4-phosphate, phosphoinositol-4,5-biphosphonate, pyrophosphate, phosphoethanolamine-diethylenetriamine-pentaacetate, dinitrophenyl-phosphoethanolamine, and phosphoglycerol,
• the method comprising:
• providing a first compound having a glycerolic backbone and at least one free hydroxyl group, said first compound having Formula I:
• wherein A1 and R1 are as, defined for Formula II, and R3 is selected from the group consisting of hydrogen, alkyl, and aryl;
• providing a second compound having at least one unsaturated bond and at least one reactive group capable of forming an ether bond with said free hydroxyl group;
• reacting said first compound and said second compound to thereby obtain a third compound, said third compound having a glycerolic backbone and an unsaturated bond-containing residue being attached to said glycerolic backbone via an ether bond;
• isolating said third compound, to thereby obtain a purified third compound;
• reacting said purified third compound with an oxidizing agent comprising a mixture of a periodate and a permanganate, to thereby obtain a fourth compound, said fourth compound having a glycerolic backbone and an oxidized moiety-containing residue attached to said glycerolic backbone via an ether bond, wherein said oxidized moiety is a carboxylic acid group;
• and
• isolating said fourth compound to thereby obtain a purified fourth compound, thereby obtaining the compound having a glycerolic backbone and at least one oxidized moiety-containing residue attached to said glycerolic backbone via an ether bond.