The synthesis of a geminally perfluoro-tert-butylated beta-amino acid and its protected forms as a potential pharmacokinetic modulator and reporter for peptide-based pharmaceuticals

To modulate and report the pharmacokinetics of peptide-based pharmaceuticals, a novel geminally perfluoro-tert-butylated beta-amino acid (betaFa) and its Fmoc- and Boc-protected forms were designed and synthesized. betaFa was incorporated into a model tripeptide via standard solid-phase chemistry. Both the amino acid (free and protected) and the tripeptide show a sharp singlet 19F NMR signal. Reversed-phase chromatography and 1-octanol/water partition measurements demonstrate that betaFa is extremely hydrophobic.