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Coupling Reactions

Amide

Peptide bond formation on solid phase and in solution.

Solid Phase

  • Uronium-Based Coupling -- HATU, HBTU, COMU, and related uronium/guanidinium reagents.
  • Phosphonium Reagents -- PyBOP, PyAOP, and related phosphonium coupling agents.
  • Carbodiimide -- DIC-mediated coupling, typically with HOAt or HOBt as additive.
  • BTC -- Triphosgene-mediated coupling for sterically hindered substrates.

Solution Phase

  • DCC -- Dicyclohexylcarbodiimide coupling.
  • EDC -- Water-soluble carbodiimide for aqueous-compatible couplings.
  • CDI -- Carbonyldiimidazole-mediated activation.
  • Solution-Phase Amide Coupling with DSC -- Disuccinimidyl carbonate activation.
  • Active Esters -- Pre-formed active esters (e.g., NHS esters, pentafluorophenyl esters).

Other Reagents to Consider

  • Acid fluoride (TFFH, cyanuric fluoride)
  • Acid chloride (BTC, trichloroacetonitrile, thionyl chloride)
  • T3P
  • EEDQ and IIDQ
  • Triazines
  • PyBrOP

Ester

Solid Phase

Peptoid

Solid Phase