Synthesis of 4,6‐Difluoro‐Tryptophan as a Probe for Protein ¹⁹F NMR

A scalable procedure for the synthesis of 4,6‐difluorotryptophan is reported based on a deaminative coupling of a 4,6‐difluorogramine with 2‐benzylthio‐1,5‐dihydro‐4 H ‐imidazolone as glycine equivalent. Thus prepared 4,6‐difluorotryptophan was incorporated into the C‐terminal domain of the HIV‐1 capsid protein (CA‐CTD), and 19 F spectra of the 4,6‐difluoro Trp CA CTD were recorded and compared to the singly fluorinated counterparts.