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

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...

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Bibliographic Details
Published in:European journal of organic chemistry 2017-02, Vol.2017 (5), p.1019-1024
Main Authors: Pekošak, Aleksandra, Rotstein, Benjamin H., Collier, Thomas L., Windhorst, Albert D., Vasdev, Neil, Poot, Alex J.
Format: Article
Language:English
Subjects:
Asymmetric catalysis
Diastereoselectivity
Isotopic labeling
Peptides
Radiochemistry
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Summary: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. Phase‐transfer catalysis now allows asymmetric multistep carbon‐11 peptide radiolabeling. The 11C–C bond formation proceeds with high radiochemical conversions and high levels of diastereoselectivity. The optimal use of chiral phase‐transfer catalysis furnishes unprecedented native, that is, unmodified, 11C‐labeled peptides for positron emission tomography imaging.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.201601641