Synthesis of potential dual binding site acetylcholinesterase inhibitors through an efficient solid phase approach based on the Mitsunobu reaction

A solid phase synthesis of a number of monoamino and diamino derivatives as potential dual binding site AChE inhibitors was developed. Our synthetic protocol was characterized by a series of three consecutive Mitsunobu reactions. The loading of the first building block, a dimethylaminophenol, onto the brominated Wang resin was efficiently carried out with DIAD and PPh3 in THF, whereas the two subsequent Mitsunobu reactions, allowing the introduction of an aliphatic spacer linked to a second phenolic moiety, resulted in higher yields when performed with ADDP and PBu3 in CH2Cl2. The scheme adopted in this synthesis could allow an easy and straightforward entry to libraries of amines of the general formulae A and B.