Fmoc Amino Acid Fluorides: Convenient Reagents for the Solid-PhaseAssembly of Peptides Incorporating Sterically Hindered Residues

Abstract

Fmoc amino acid fluorides, recently shown to be a new class of rapid- acting acylating agents in peptide synthesis are well suited for the solid-phase synthesis of medium-sized peptides such as ACP(65-74), ma- gainin-II-amide, and h-CRF. The most important advantage of these rea- gents is their high reactivity in the coupling of sterically hindered amino acid residues, such as α-aminoisobutyric acid (Aib), results whi- ch are at least partly due to the small size of the fluoride leaving group. Both h-(Aib 32-35 )-CRF(1-41), bearing four consecutive Aib- residues, and alamethicin acid, neither previously accessible by solid- phase synthesis, were successfully synthesized via acid fluorides using unusually short coupling times. I n contrast, attempted syntheses via UNCA's and PyBroP activation, both reported to be well suited for steri- cally hindered systems, failed to give the desired peptides