Rapid synthesis of dendrimers by an orthogonal coupling strategy

Dendrimers are polymers that radiate out from a central core, with the number of branch points on a given arm increasing exponentially from the core to the periphery. 1 Because of their novel properties, dendrimers have found many uses, including as unimolecular micelles, 2 novel amphiphiles, 3 complexation agents, 4 and MRI contrast agents. 5 These and other applications will benefit from more efficient methods of dendrimer preparation because the iterative synthetic approaches to even small dendrons are multistep. In particular, both the divergent approach developed by Tomalia 6 and Newkome 7 and the convergent method of Fre ́chet8 minimally require a deprotection or activation step in addition to the coupling step that adds each new generation. Several successful attempts to shorten these synthetic sequences were reported; 9-11 however, these approaches still require (de)protection or activation chemistry. Several years ago, Baranay and Merrifield 12 defined an orthogonal system as “a set of completely independent classes of protection groups, such that each class can be removed in any order and in the presence of all other classes.” Orthogonal protecting group strategies have found widespread use in peptide chemistry, and recently Ogawa 13 used two independent (orthogonal) glycosylation reactions to accelerate the synthesis of oligosaccharides. We now describe a rapid synthesis of dendrimers using an orthogonal coupling strategy wherein each synthetic step adds a generation to the existing dendrimer. 14