Synthesis and application of N‐[1‐(4‐(4‐fluorophenyl)‐2,6‐dioxocyclohexylidene)ethyl] (Fde)‐protected amino acids for optimization of solid‐phase peptide synthesis using gel‐phase ¹⁹F NMR spectroscopy

Abstract

N-[1-(4-(4-fluorophenyl)-2,6-dioxocyclohexylidene)ethyl] (Fde) protected amino acids have been prepared and applied in solid-phase peptide synthesis monitored by gel-phase (19)F NMR spectroscopy. The Fde protective group could be cleaved with 2% hydrazine or 5% hydroxylamine solution in DMF as determined with gel-phase (19)F NMR spectroscopy. The dipeptide Ac-L-Val-L-Val-NH(2) 12 was constructed using Fde-L-Val-OH and no noticeable racemization took place during the amino acid coupling with N,N'-diisopropylcarbodiimide and 1-hydroxy-7-azabenzotriazole or Fde deblocking. To extend the scope of Fde protection, the hydrophobic nonapeptide LLLLTVLTV from the signal sequence of mucin MUC1 was successfully prepared using Fde-L-Leu-OH at diagnostic positions.

Synthesis and Application of a 2-[(4-Fluorophenyl)-sulfonyl]ethoxy Carbonyl(Fsec) Protected Glycosyl Donor in Carbohydrate Chemistry

“…The Fsec group has potential to be used to protect glycosyl donors intended for solid-phase synthesis of glycoconjugates using gel-phase 19 F-NMR spectroscopy as monitoring technique. The chemical shift for the fluorine atom in the Fsec group (approximately -103 ppm) is well separated from other commonly used protecting groups, e.g., fluorine containing benzyl (-114 to -119 ppm), benzoate (-104 to -113 ppm), or benzylidene (-112 to -121 ppm) groups [ 15 ], and the recently introduced [1-(4-(4-fluorophenyl)-2,6-dioxocyclohexylidene)ethyl] (Fde) N -protecting group (approximately -116 ppm) [ 22 ]. 19 F-NMR shifts for the fluorinated protecting groups in compound 4 - 8 and 11 - 14 are given in Table 2 .…”