An Efficient Synthesis of an Orthogonally Protected Aromatic Diamine as Scaffold for Tweezer Receptors with Two Different Arms

The synthesis of a new versatile template, 3-(N-Boc-aminomethyl)-5-(N-Fmoc-aminomethyl)benzoic acid (1), was developed and is hereby reported. The key feature of the synthetic strategy is the selective mono reduction of a symmetric diazide using a biphasic reaction mixture. The mono reduction allows the sequential introduction of two orthogonal protecting groups - e.g., Fmoc and Boc. This building block can be used as a scaffold for the solid-phase synthesis of dipodal or cyclic peptidic receptors. It allows the preparation of tweezer receptors with unsymmetrically substituted side arms and therefore for the implementation of an enhanced structural and functional diversity in comparison to symmetric tweezers. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)