Application of Metal‐Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates

  title={Application of Metal‐Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates},
  author={S. van Berkel and A Ton J Dirks and Silvie A. Meeuwissen and Dennis L. L. Pingen and Otto C Boerman and Peter Laverman and Floris L. van Delft and Jeroen J. L. M. Cornelissen and Floris Rutjes},
The tandem 1,3‐dipolar cycloaddition‐retro‐Diels–Alder (tandem crDA) reaction is presented as a versatile method for metal‐free chemoselective conjugation of a DTPA radiolabel to N‐δ‐azido‐cyclo(‐Arg‐Gly‐Asp‐d‐Phe‐Orn‐) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl‐substituted oxanorbornadiene derivatives in the 1,3‐dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio‐orthogonal ligation in an aqueous environment… 

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