Skip to content

HBTU — Coupling Reagent

Standard Peptide Synthesis Activator

Definition

HBTU (O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate) is the most widely used coupling reagent in Fmoc-SPPS.


Specifications

Parameter Typical Value
Purity ≥99%
Appearance White crystalline powder
Storage -20 °C, desiccated
CAS number 94790-37-1

Activation Mechanism

  1. HBTU deprotonates Fmoc-AA-OH (assisted by base/DIEA)
  2. Forms active ester (benzotriazolyl ester)
  3. Active ester reacts with free amine on peptide

Typical Conditions

Parameter Value
Equivalents 2.9 eq (relative to AA)
Base DIEA (6 eq)
Solvent DMF
Activation time 2–5 minutes
Coupling time 30–60 minutes

Advantages

  • Widely available and cost-effective
  • Good coupling efficiency for standard amino acids
  • Compatible with automated synthesizers

Limitations

  • May cause racemization for His, Cys
  • Lower reactivity for hindered amino acids (use HATU instead)

  • Standard Peptide Synthesis Activator — Review the section above for key parameters, methods, and quality criteria.

  • Activation Mechanism — Review the section above for key parameters, methods, and quality criteria.
  • Typical Conditions — Review the section above for key parameters, methods, and quality criteria.

Key Takeaways

  • Standard Peptide Synthesis Activator — Review the section above for key parameters, methods, and quality criteria.
  • Definition — Review the section above for key parameters, methods, and quality criteria.
  • Specifications — Review the section above for key parameters, methods, and quality criteria.
  • Activation Mechanism — Review the section above for key parameters, methods, and quality criteria.

🔗 Related: HATU | DIC | Oxyma | Coupling Reaction