Stereocontrolled [11C]Alkylation of N‐Terminal Glycine Schiff Bases To Obtain Dipeptides

• Published in: European journal of organic chemistry Vol. 2017; no. 37; pp. 5592 - 5596
• Main Authors: Filp, Ulrike, Pekošak, Aleksandra, Poot, Alex J., Windhorst, Albert D.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 10.10.2017; Wiley Subscription Services, Inc
• Subjects: Alkylation; Asymmetric synthesis; Catalysis; Chemistry; Chemistry, Organic; C–C coupling; Glycine; Halides; Imines; Peptides; Phase transfer catalysts; Physical Sciences; Positron emission; Positron emission tomography; Quaternary ammonium salts; Radiochemistry; Science & Technology; C-C coupling; ALPHA-AMINO; DESIGN; ASYMMETRIC-SYNTHESIS; Peptides; Asymmetric synthesis; ENANTIOSELECTIVE SYNTHESIS; AMINO-ACIDS; ALKYLATION; Radiochemistry; Positron emission tomography; PHASE-TRANSFER CATALYSTS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201701129

The use of various quaternary ammonium salts as chiral phase‐transfer catalysts allowed effective and stereoselective radiochemical [11C]alkylation to obtain functionalized dipeptides. We herein report a broadly applicable procedure for the asymmetric [11C]alkylation of dipeptides to give labeled N‐terminal peptides by using different [11C]alkyl halides. Contended stereoselectivities of the reactions were observed by using 11C‐labeled alkyl halides, [11C]methyl iodide and [11C]benzyl iodide, and diastereomeric ratios with different specialized catalysts of 95:5 and 90:10 were achieved, respectively. Accordingly, the straightforward synthesis of enantioenriched compounds should play a vital role in peptide‐based radiopharmaceutical development and positron emission tomography imaging. Herein, the diastereoselective alkylation of the Ph2Gly‐l‐Val‐OtBu Schiff base precursor towards the synthesis of favored (red) or unfavored (blue) carbon‐11‐labeled dipeptides is reported.