SiFA‐Modified Phenylalanine: A Key Compound for the Efficient Synthesis of 18 F‐Labelled Peptides

• Published in: European journal of inorganic chemistry 2011-05, Vol.2011 (14), p.2238-2246
• Main Authors: Iovkova, Ljuba, Könning, Daniel, Wängler, Björn, Schirrmacher, Ralf, Schoof, Sebastian, Arndt, Hans‐Dieter, Jurkschat, Klaus
• Format: Article
• Language: English
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201100142

Both the racemic and the stereoselective synthesis of the silicon‐modified amino acid p ‐( t Bu 2 FSi)C 6 H 4 CH 2 (NH 2 )COOH (SiFA‐phenylalanine, 6 ) and its derivatives p ‐( t Bu 2 FSi)C 6 H 4 CH 2 (NHBoc)COOH ( 10 ) and p ‐( t Bu 2 FSi)C 6 H 4 CH 2 (NHFmoc)COOH ( 11 ) are reported. The latter two compounds are valuable building blocks for the convenient introduction of silicon‐based fluoride acceptors (SiFAs) into peptides by solid‐phase peptide syntheses (SPPS). As prove of principle, the Tyr 3 ‐octreotate derivatives 12 , 13 and 14 were prepared by using standard protocols of the solid‐phase peptide synthesis (SPPS). They were labelled with 18 F‐fluorine by isotopic exchange in radiochemical yields of up to 70 % (with radiochemical purity ranging between 92 and 99 %). The incorporation of 18 F‐fluorine into the SiFA‐modified amino acid 6 was studied as the latter may also serve as a tracer in PET. After purification, [ 18 F]‐ 6 showed a remarkable stability in an isotonic solution. Also reported is the molecular structure, as determined by single‐crystal X‐ray diffraction analysis, of p ‐( t Bu 2 FSi)C 6 H 4 CHCH[C(O)OMe]NHC(O)OCH 2 Ph ( 8 ), which serves as a precursor for the stereoselective synthesis of compound 6 .