Esters of acyl L-carnitines with gamma-hydroxybutyric acid and pharmaceutical compositions containing them for inhibiting neuronal degeneration and for the treatment of coma

Claim 1

A process for preparing esters of acyl L-carnitines with gamma-hydroxybutyric acid of general formula (I) wherein X⁻ is the anion of a pharmacologically acceptable acid and R is a straight or branched acyl group having 2-5 carbon atoms, which comprises: (1) condensing an acyl L-carnitine inner salt with gamma-bromobutyric acid benzyl ester in an anhydrous organic solvent inert towards the reactants, at a temperature comprised between 20°C and 30°C, for 10-24 hours in an inert gas atmosphere and isolating the product thus obtained, acyl L-carnitine bromide ester with gamma-hydroxybutyric acid benzyl ester, from the reaction mixture via precipitation with an anhydrous organic solvent, such as acetonitrile or ethyl ether; (2) hydrogenating the compound obtained in step (1) in water or absolute ethanol solution in the presence of 5% or 10% Pd/C catalyst, for 30-60 minutes, at a pressure of 2-5 hydrogen atmospheres and isolating the product thus obtained, acyl L-carnitine bromide ester with gamma-hydroxybutyric acid, by concentrating under vacuum the solution to dryness; and (3) dissolving the compound obtained in step (2) in water or methanol and eluting the solution through a strongly basic ion exchange resin, such as AMBERLITE IRA 402 or AMBERLIST A26 activated in Cl⁻ or HCO₃⁻ form, lyophilizing the aqueous solution or concentrating under vacuum the methanol solution eluted from the resin, thus obtaining acyl L-carnitine chloride ester with gamma-hydroxybutyric acid or the inner salt thereof.