N-Aminoimidazolone (Nai) peptide mimics were synthesized with minimal epimerization by base-promoted 5-endo-dig cyclization of aza-propargylglycine dipeptide acids and hydrazides followed by olefin migration. 5-Position functionalization using Mannich amino methylation and Vilsmeier–Haack formylation has given access to a set of restrained side chain analogs of Asp, Dab, and Hse residues for mimicry of turn form and function.
Fifteen N-aminoimidazolone
(Nai) dipeptides having
a variety of 5-position side-chain groups were synthesized by regioselective
proline-catalyzed reactions of azopeptide and aldehyde components
followed by acid-mediated dehydration of an aza-aspartate semialdehyde
intermediate. The introduction of 5-aryl-Nai dipeptides into cluster
of differentiation 36 receptor (CD36) peptide ligands has provided
insight into the conformation responsible for binding affinity and
anti-inflammatory activity.
N-Amino-imidazol-2-one (Nai) residues are tools for studying peptide-backbone and side-chain conformation and function. Recent methods for substituted Nai residue synthesis, conformational analysis by X-ray crystallography and computation, and biomedical applications are reviewed, demonstrating the utility of this constrained residue to favor biologically active turn conformers with defined χ-dihedral angle orientations.1 Introduction2 Synthetic Methods3 Conformational Analysis4 Biomedical Applications5 Conclusions
N′-Alkyl hydrazides were effectively synthesized by routes featuring installation, alkylation, and removal of a trifluoroacetyl group. A set of amino acid derived hydrazides were acylated using trifluoroacetic anhydride, and the resulting trifluoroacetyl hydrazides were alkylated with alcohols in Mitsunobu reactions and with alkyl halides under alkaline conditions. Removal of the trifluoroacetyl group was affected under reductive and hydrolytic conditions to provide the respective N′-alkyl hydrazides. This three-step process may be performed without isolation of intermediates to yield N′-alkyl hydrazide after a single chromatographic purification.
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