Synthesis of Archaeal Bipolar Lipid Analogues:  A Way to Versatile Drug/Gene Delivery Systems

A synthetic route for the preparation of symmetrical and unsymmetrical archaeal tetraether-like analogues has been described. The syntheses are based upon the elaboration of hemimacrocyclic tetraether lipid cores from versatile building blocks followed by simultaneous or sequential introduction of polar head groups. Functionalizations of the tetraether lipids with neutral lactose or phosphatidylcholine polar heads and cationic glycine betaine moieties were envisaged both to increase membrane stability and to exhibit interactions with charged nucleic acids. Additionally, mannose and lactose triantennary clusters designed as multivalent ligands for selective interaction with lectin-type receptors were also efficiently synthesized for active cell/tissue targeting.