Bis(BOC) amino acid fluorides as reactive peptide coupling reagents

Amino acid fluorides: viable tools for synthesis of peptides, peptidomimetics and enantiopure heterocycles

“…Carpino et al have also reported the synthesis of bis(Boc)-amino acid uorides and utilized them in the synthesis of [Leu 5 ] enkephalin. 91 N,N-Dialkoxycarbonyl amino acid uorides were found to withstand purication on silica gel and were isolated as stable compounds. Small and variable amounts of the urethane-N-carboxyanhydrides (UNCAs) formed during acid uoride formation may also be separated by cooling the hexane treated crude residue in a refrigerator followed by ltration.…”

Methods for the Peptide Synthesis and Analysis

“…Thus, Fmoc-based SPPS can be easily carried out through Fmoc amino acid fluorides [88][89][90][91][92][93][94].…”

Protection Reactions

“…However, enolization through base-catalyzed a-proton exchange (leading to racemization) can be promoted by the presence of an additional electron-withdrawing substituent on the a-amino group. This can be minimized through rapid couplings by using highly active Boc 2 -amino acid fluorides as acylating agents [126,128]. However, N a ,N a -bis-Boc protected dipeptides with C-terminal Gly show an increased tendency to form hydantoins rather than the corresponding Boc-dipeptides.…”