1. Introduction Dendrimers are synthetic macromolecules with a tree-like structure based on repetitive branching from a core. This type of growth leads to macromolecules rapidly increasing in size and molecular weight making them well-defined, covalently bound nanoparticles. Dendrimers are also an example of a class of compounds, where the potential applications always have been way ahead of the synthetic chemistry needed to make them. This is probably because they were born in industrial laboratories as potential products for commercialization . There are potential applications of dendrimers in a number of different areas ranging from diagnostics, nanomedicine, nanotechnology to cosmetics due to their properties. The dendritic architecture provides a multivalent surface, which can be used for amplifying weak interactions between a ligand and a receptor as demonstrated with glycodendrimers , for vaccines (MAPs) or as artificial receptors . The nanometer size of dendrimers allows targeting of cancer tumors using the enhanced permeation retention-effect (EPR) . Amino-terminated dendrimers form complexes with DNA or siRNA that can be used for transfection as well as siRNA-therapy and the interior cavities can be used as molds for synthesizing well-defined nanoparticles . The interior may also be used to hold drug molecules for transport. Most dendrimers reported have simple structures with one type of branch cell and one type of surface group or a statistical distribution of surface groups, while well-defined dendrimers with a well-defined heterogenous surface are mainly limited to peptide dendrimers made by solid phase peptide synthesis (SPPS) . There are two different strategies that can be applied for synthesizing dendrimers with a well-defined surface chemistry; symmetry-breaking reactions on a preformed symmetrical dendrimer (which in essence is a protective group-free synthesis) or synthesis by convergent synthesis involving suitably protected building blocks. Symmetry-breaking reactions on preformed dendrimers such as amino-terminated dendrimers reflects the fact, that it is possible to achieve chemoselectivity in acylations on polyamines (see for example reference and references therein). However due to the small differences in reactivity between the unmodified dendrimer and the partially acylated products mixtures are formed that require chromatographic separation of the products putting serious limitations to this approach . In this paper we present a general synthetic methodology that allows synthesis of small generation, but well-defined structurally diverse PAMAM-dendrimers. Access to precisely functionalized dendrimers will make systematic studies of structure-activity relations between dendrimers and biological systems possible. The only previous examples of unsymmetrical PAMAM-dendrimers are Janus-dendrimers and partially acylated G0 PA-MAMs .