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Stereoselective 11 C Labeling of a “Native” Tetrapeptide by Using Asymmetric Phase‐Transfer Catalyzed Alkylation Reactions
Author(s) -
Pekošak Aleksandra,
Rotstein Benjamin H.,
Collier Thomas L.,
Windhorst Albert D.,
Vasdev Neil,
Poot Alex J.
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201601641
Subject(s) - tetrapeptide , chemistry , alkylation , stereoselectivity , stereocenter , stereochemistry , combinatorial chemistry , pharmacophore , enantioselective synthesis , peptide , catalysis , organic chemistry , biochemistry
The first 11 C‐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, [ 11 C]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 11 C‐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.