β-Nitro-α-amino acids as latent α,β-dehydro-α-amino acid residues in solid-phase peptide synthesis

Abstract

β-Nitro-α-amino acids, that are readily accessible through either the reaction of bromoglycine derivatives with alkyl nitronates or the three-component coupling of amines, nitroalkanes and glyoxalate in aqueous base, are easily converted to the corresponding N-t-Boc-amino acids. These undergo solid-phase Merrifield peptide synthesis, with elimination of nitrous acid, either during or subsequent to cleavage of the peptide from the resin, converting the nitro amino acids to dehydro amino acid residues. The method has been applied successfully with two β,β-disubstituted nitro amino acids and N-methyl-β-nitronorvaline, but failed with β-nitroalanine.

Synthesis and Studies of Bulky Cycloalkyl α,β-Dehydroamino Acids that Enhance Proteolytic Stability

“…A handful of cycloalkyl ΔAAs are known, but they have primarily been used as substrates for enantioselective hydrogenations . We are only aware of two reports describing their incorporation into peptides …”