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

Both the racemic and the stereoselective synthesis of the silicon-modified amino acid p-(tBu(2)FSi)C6H4CH2(NH2) COOH (SiFA-phenylalanine, 6) and its derivatives p-(tBu(2)FSi)C6H4CH2-(NHBoc)COOH (10) and p-(tBu(2)FSi)C6H4CH2-(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 F-18-fluorine by isotopic exchange in radiochemical yields of up to 70% (with radiochemical purity ranging between 92 and 99%). The incorporation of F-18-fluorine into the SiFA-modified amino acid 6 was studied as the latter may also serve as a tracer in PET. After purification, [F-18]-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-(tBu(2)FSi)C6H4CHCH[C(O)OMe]NHC(O)-OCH2Ph (8), which serves as a precursor for the stereoselective synthesis of compound 6.