Regioselective synthesis of folic acid conjugates from diether-type archaeal lipid analogues

A regioselective access to both α- and γ-folic acid conjugates derived from archaeal lipid analogues is described. The synthetic approach is based on conveniently protected glutamates that led first to α- and γ-glutamate derivatives. The final reconstruction of the folic acid moiety was achieved through the reaction of a protected/activated pteroate followed by a simple deprotection step. These α- and γ-folic acid conjugates would permit to establish the importance of a regiocontrolled introduction of folic acid on the folic acid/folate receptor interaction in the case of a targeted drug/gene delivery.