Solid-Phase Synthesis of Tetrahydropyridazinedione-Constrained
Peptides
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Abstract
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