Process for synthesis of novel cationic amphiphiles containing N-hydroxyalkl group for intracellular delivery of biologically active molecules

A process for the synthesis of novel cationic amphiphiles that facilitate intracellular delivery of biologically active molecules, said amphiphiles represented by the following structural formula (I):

• wherein:
• n is an integer between 1 and 3;
• R1 independently, represents either a saturated aliphatic group or an unsaturated aliphatic group (from C8 to C20);
• Z represents a methylene (—CH2—) group;
• R2, independently, represents a long-chain saturated alkyl group (from C7 to C19);
• R3 is a small allyl group (from C1 to C3);
• X is either a halogen atom or a tosylate group,
• said process comprising the steps of:
• (a) coupling an appropriate aliphatic saturated or unsaturated aldehyde with an alkyl amine followed by the reduction of the resulting imine to obtain the corresponding secondary amine;
• (b) reacting the secondary amine obtained in step (a) with the appropriate hydroxyl-protected hydroxyalkyl halide followed by removal of the hydroxyl protecting group to obtain the corresponding N-hydroxyalkyl group containing tertiary amine, and
• (c) quaternizing the resulting N-hydroxyalkyl group containing tertiary amine obtained in step (b) with the appropriate alkyl halide or alkyl tosylates in a mixed polar solvent.