Synthesis of folate lipoconjugates with hydrophobic spacers

Abstract

Folate lipoconjugates were synthesized by induction of spacers to 1,2-di-O-tetradecyl-rac-glycerol for future condensation with folic acid. The intermediates hydrophobic compounds were obtained by treatment of 1-О-(4- nitrophenyloxycarbonyl)-2,3-di-O-tetradecyl-rac-glycerol with free diamines (1,4-diaminobutane, 1,6-diaminohexane, 1,8-diaminooctane, 1,12-diaminododecane) in the presence of triethylamine. Condensation of intermediate compounds (1 eq.) and folic acid (3 eq.) were carried out in the presence of (O-(benzotriazol-1-yl)- 1,1,3,3-tetramethyluronium tetrafluoroborate (3 eq.) and N,N-diisopropylethylamine (5 eq.) and gave targeted folate lipoconjugates. The structures and purity of the compounds synthesized were confirmed by analytic physicochemical methods.

Keywords

• folic acid, targeting delivery, cancer cells.