2 research outputs found
Solid-Phase Synthesis of Tetrahydropyridazinedione-Constrained Peptides
The
design and solid-phase synthesis of tetrahydropyridazine-3,6-dione
(Tpd) peptidomimetics derived from backbone-aminated peptides is reported.
The described protocol features the synthesis of chiral α-hydrazino
acids suitable for chemoselective incorporation into growing peptide
chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage
affords the target peptidomimetics in good yield and purity. The scope
of Tpd incorporation is demonstrated through the synthesis of constrained
peptides featuring nucleophilic/electrophilic side chains and sterically
encumbered α-substituted hydrazino acid residues
Access to Enantiopure α‑Hydrazino Acids for <i>N</i>‑Amino Peptide Synthesis
Backbone <i>N</i>-methylation of α-peptides has
been widely employed to enhance the bioavailability and bioactivity
of parent sequences. Heteroatomic peptide amide substituents have
received less attention due, in part, to the lack of practical synthetic
strategies. Here, we report the synthesis of α-hydrazino acids
derived from 19 out of the 20 canonical proteinogenic amino acids
and demonstrate their use in the solid-phase synthesis of <i>N-</i>amino peptide derivatives