Chemoselective Staudinger Reactions – Powerful Tools for Organic Synthesis and Chemical Biology Prof. Dr. Christian P. R. Hackenberger, Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195 Berlin, Germany hackenbe@chemie.fu-berlin.de Chemoselective reactions have become important tools organic synthesis[1] as well as in modern life science, since they allow the study of biological and functional aspects of protein modifications.[2] Recently, we have identified the Staudinger- phosphite reaction as a bioorthogonal transformation for the functionalization of azides under mild conditions in high yields.[3] In this presentation several examples for the synthesis of phosphite building blocks and their applications for the metal-free functionalization of peptides and proteins are given to deliver phosphoramidate-linked conjugates.[3-5] These applications include the chemical phosphorylation of proteins, in which charged phosphoramidates are generated that can be recognized by phosphotyrosine-specific antibodies (see Scheme). Furthermore, examples for the conjugation of PEGs, carbohydrates and biotin as well as further variants of the Staudinger reaction to yield phosphonamidate- conjugates are presented.[3,5,6] [1] For reviews on protecting-group-free synthesis in the total synthesis of natural products, see: a) R. W. Hoffmann, Synthesis 2006, 21, 3531; b) I. S. Young, P. S. Baran, Nature Chemistry 2009, 1, 193. [2] a) J. A. Prescher, C. R. Bertozzi, Nat. Chem. Biol. 2005, 1, 13. b) E. M. Sletten, C. R. Bertozzi, Angew. Chem. Int. Ed. 2009, 48, 6974; c) B. L. Nilsson, M. B. Soellner, R. T. Raines, Annu. Rev. Biophys. Biomol. Struct. 2005, 34, 91. d) C. P. R. Hackenberger, D. Schwarzer, Angew. Chem. Int. Ed. 2008, 47, 10030. [3] R. Serwa, I. Wilkening, G. del Signore, M. Mühlberg, I. Claußnitzer, C. Weise, M. Gerrits, C. P. R. Hackenberger, Angew. Chem. Int. Ed. 2009, 48, 8234. For the first report on the Staudinger ligation with phosphines, see: E. Saxon, C. R. Bertozzi, Science 2000, 287, 2007. [4] V. Böhrsch, R. Serwa, P. Majkut, E. Krause, C. P. R. Hackenberger, Chem. Commun. 2010, 46, 3176. [5] R. Serwa, P. Majkut, B. Horstman, J.-M. Swiecicki, M. Gerrits, E. Krause, C. P. R. Hackenberger, Chemical Science 2010, 1, 596. [6] I. Wilkening, G. del Signore, C. P. R. Hackenberger, Chem. Commun. 2011, 47, 349.