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

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• 作者：Aleksandra Pekošak ; Benjamin H. Rotstein ; Thomas L. Collier ; Albert D. Windhorst ; Neil Vasdev and Alex J. Poot
• 刊名：European Journal of Organic Chemistry
• 出版年：2017
• 出版时间：February 03, 2017
• 年：2017
• 卷：2017
• 期：5
• 页码：1019-1024
• 全文大小：1566K
• ISSN：1099-0690

文摘

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.