Toward the Next-Generation Drug Delivery Vehicle: Synthesis of a Dendrimer with Four Orthogonally Reactive Groups

The synthesis of a dendrimer based on melamine that displays multiple copies of four orthogonally reactive groups, three on the surface and one on the interior, is described. The three groups on the surface are nucleophilic and include four free hydroxyl groups, four hydroxyl groups masked as tert-butyldiphenylsilyl (TBDPS) ethers, and 16 amines masked as tert-butoxycarbonyl (BOC) groups. The core of the dendrimer displays two electrophilic monochlorotriazines. The dendrimer is available in seven linear steps (eight total steps) at 55% overall yield for the longest linear sequence.