Designing Silylated L -Amino Acids using a Wittig Strategy: Synthesis of Peptide Derivatives and 18 F-Labelling

Abstract : An efficient semisynthesis of silylated l-amino acids by reaction of silylated benzaldehydes with a phosphonium l-amino acid used as a Wittig reagent is described. The efficiency of the silylated l-amino acids in peptide synthesis was investigated by coupling both the carboxylic acid and the amino moiety with l-alanine and phenylalanine derivatives, respectively. The silylated derivatives were treated with KF or tetrabutylammonium fluoride to give the corresponding fluorosilyl derivatives without racemization. The hydrolysis of the fluorosilylated derivatives in phosphate buffer at pH 7.2 was checked. Finally, the 18F-labelling of di-tert-butylsilylated saturated and unsaturated dipeptides was achieved in hot DMSO with a mixture of K[18F]/cryptand (K2.2.2) and acetic acid. The 18F-labelled dipeptides were obtained with radiochemical yields and molar activities of up to 31 % and 410 GBq/µmol, respectively. Consequently, this semisynthesis involving a Wittig reaction offers a new and efficient route for the design and 18F-labelling of Si-based amino acids and peptide derivatives, which may find applications in PET imaging.