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Solid-Phase Synthesis of Tetrahydropyridazinedione-Constrained Peptides

[Image: see text] 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...

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Detalles Bibliográficos
Autores principales: Kang, Chang Won, Ranatunga, Sujeewa, Sarnowski, Matthew P., Del Valle, Juan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201324/
https://www.ncbi.nlm.nih.gov/pubmed/25295511
http://dx.doi.org/10.1021/ol5026684
Descripción
Sumario:[Image: see text] 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.