Synthesis of (2S,4S)- and (2S,4R)-5-fluoroleucine and (2S,4S)-[5,5-2H2]-5-fluoroleucine

Abstract

Syntheses of (2S,4S)- and (2S,4R)-5-fluoroleucine, 1a and 2, and of (2S,4S)-[5,5-²H₂]-5-fluoroleucine, 1b, have been completed. The methodology allows these compounds to be prepared in sufficient quantities for incorporation by solid-state protein synthesis into strategic sites in proteins for folding studies. X-ray structures of the epimers 1a and 2 have been obtained and show the presence of conformational isomerism. The torsion angles between the F–C bond and the main chain are compared with values found in a mutant of the protein ubiquitin in which (2S,4S)-5-fluoroleucine replaces leucine residues 50 and 67 in the native protein.