Synthesis of dendrons with bone targeting moieties

Abstract

Macromolecules containing multifunctional groups are promising candidates for drug delivery systems because a multivalent interaction between biological receptor and a targeting molecule increases the binding strength. Since dendrimers have high density and wide variety of functional groups on their surface, they are emerging as potential vehicles in drug delivery systems. Accomplishment of targeted drug delivery to bone tissues will be instrumental in curing bone related diseases. Dendrimers with appropriate bone targeting ligands could be promising delivery agents to the bone. This study reports synthesis of different generations of biodegradable polyester dendritic compounds containing bone targeting bisphosphonate groups. Bisphosphonates can play an important role in drug delivery to bone tissues due to their strong affinity towards hydroxyapatite in bone tissue. Biodegradable polyester dendrons were synthesized using a divergent synthetic route. The surface of the dendrons consisted of hydroxyl groups that were reacted with tetraethyl [2- (2,2-dimethyl-4,6-dioxo-1,3-dioxan-5yl)ethan-1,1-diyl] bisphosphonate to afford multivalent bisphosphonate containing dendrons in good yields. Following the attachment of bisphosphonate groups onto the dendrons, deprotection studies of phosphonate esters were carried out. The deprotections of all the bisphosphonates were met with limited success in higher generations. Future studies are needed to optimize the final deprotection step before a drug molecule can be attached to the core of these dendrons.