Dendrimers are highly branched well-defined macromolecules with a monodisperse architecture. Dendrimers have been applied in targeted delivery of active molecules into cancer cells taking advantage of the enhanced permeability and retention (EPR) effect and active targeting. The uniqueness of dendrimers comes from the possibility to introduce multiple functionalities at specific sites of the dendritic backbone, which can be used to attach drugs, imaging agents, solubilizing units and targeting agents.<br/>Astonishingly, many multifunctional dendrimers have been synthesized using the random-statistical approach that results in complex dendrimer mixtures with significant batch-to-batch variations. Although there are some methodologies to synthesize bifunctional dendrimers and even few methodologies for trifunctional dendrimers, there is a lack of methods to obtain well-defined dendrimers with a high number of distinct functionalities. In this context, our research group has focused on the development of a synthetic methodology that enables the synthesis of polyamide dendrimers carrying a large number of different functionalities, for instance up to five different functional groups.<br/>Our strategy is based on the synthesis of ABC-type dendrons through two controlled sequential Michael additions between a nitroalkane and different acrylic ester derivatives. This is possible due to controlled formation of the mono-Michael adduct which is favored in our reactional conditions. Our products were obtained in high yields, and as a proof-of-concept, we have synthesized a trifunctional third-generation polyamide dendrimer and a pentafunctional fourth-generation polyamide dendrimer. We believe that our synthetic methodology can be applied to obtain several multifunctional dendrimers with well-defined structures, assisting dendrimer-based formulations to advance with into clinical trials.

New synthetic methodology to construct well-defined multifunctional polyamide dendrimers via controlled Michael addition

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.