Stereoselective 11C Labeling of a “Native” Tetrapeptide by Using Asymmetric Phase‐Transfer Catalyzed Alkylation Reactions

Abstract

The first 11C‐labeled unmodified (“native”) peptide is described by alkylation of a tetrapeptide Schiff base, which was achieved by an automated five‐step radiochemical reaction. In a proof‐of‐concept study, [11C]Phe‐d‐Trp‐Lys‐Thr was synthesized. This tetrapeptide is the essential pharmacophore of octreotide, an antagonist of somatostatin receptors. The asymmetric alkylation with chiral phase‐transfer catalysts enabled direct labeling of a variety of isolated 11C‐peptides in a highly stereoselective manner (94 % de) with acceptable radiochemical yields (9–10 %) and practical specific activities (15–35 GBq µmol–1 or 405–945 mCi µmol–1) at the end of synthesis. This novel methodology provides a powerful new radiosynthetic method to access novel, stereochemically pure carbon‐11‐labeled native small peptides ready for in vivo studies.