Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides

Org Lett. 2014 Oct 17;16(20):5434-7. doi: 10.1021/ol5026684. Epub 2014 Oct 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • Fluorenes / chemistry
  • Molecular Structure
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptidomimetics
  • Pyridazines / chemical synthesis*
  • Pyridazines / chemistry
  • Solid-Phase Synthesis Techniques*

Substances

  • Fluorenes
  • Peptides
  • Peptidomimetics
  • Pyridazines