New fMLF-OMe Analogues Containing Constrained Mimics of Phenylalanine Residue

Sterically HinderedCα,α-Disubstituted α-Amino Acids: Synthesis from α-Nitroacetate and Incorporation into Peptides

“…In our work, the coupling of the carboxyl group of Dbg using PyAOP proved relatively efficient, but acylation of the N -terminal Dbg turned out to be very difficult. The same problem was also encountered in solution-phase synthesis of peptides containing a Dbg residue . In our studies, coupling of Fmoc-Lys(Boc)-OH onto the N -terminus of Dbg on PAL resin using PyAOP or PyAOP/HOAt were ineffective (Table , entries 1, 2), even though PyAOP has been shown to be efficient for acylation of ααAAs with less-hindered side chains, such as dipropylglycine and Aib .…”

“…Incorporation of Dbg into Peptides Using SPPS. Dbg has been previously incorporated into peptides using solution-phase peptide synthesis, and the prevalent method was using 2-trifluoromethyl-4,4-dibenzyloxazolin-5-one as the Dbg precusor. 18a, The sterically hindered Dbg inhibits efficient peptide bond formation. In our work, the coupling of the carboxyl group of Dbg using PyAOP proved relatively efficient, but acylation of the N -terminal Dbg turned out to be very difficult.…”

“…More sterically hindered ααAAs such as Dbg are much more difficult to incorporate. For example, reported acylation of the N -terminus of Dbg only gave a low to moderate coupling yield after prolonged reaction time . In this paper, we report an efficient method for readily incorporating amino acid residues to sterically hindered N -terminus of Dbg.…”

Efficient Acylation of theN-Terminus of Highly HinderedCα,α-Disubstituted Amino Acids via Amino Acid Symmetrical Anhydrides

“…For example, incorporation of Dbzg or TOAC onto a growing peptide chain was readily accomplished by activated ααAA oxazolones or traditional HBTU coupling reagent . In contrast, acylation of the N -terminus of Dbzg or TOAC with DCC/HOBt, mixed anhydride, or HATU only gave low to moderate yields. , Thus the difficulties in incorporating sterically hindered ααAAs into internal positions of peptide chains mainly stem from the inefficient acylation of the ααAA N -termini. Herein we report a convenient method for the high yield acylation of the N -terminus of sterically hindered ααAAs using amino acid symmetrical anhydrides in the absence of base.…”