PyAOP | CAS 156311-83-0 | ≥98%

PyAOP — (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate — is a phosphonium peptide-coupling reagent and the HOAt-derived analogue of PyBOP. In the presence of a tertiary amine base, it converts carboxylic acids to OAt active esters, which then acylate amines to form amide bonds. The HOAt-derived leaving group gives more reactive OAt esters than the OBt esters formed by PyBOP, because HOAt has a lower pKa and its pyridine nitrogen provides neighbouring-group assistance; PyAOP is therefore used for fast, low-racemisation couplings. As a phosphonium salt, it avoids the N-terminal guanidinylation side reaction associated with uronium/aminium reagents such as HATU, so excess PyAOP can be used in slow cyclisation and fragment couplings without blocking the free amine terminus. PyAOP is supplied as a white to colourless crystalline solid, soluble in DMF, dichloromethane, acetonitrile, NMP, THF and related organic solvents; solutions should be prepared fresh for best performance.

Common Scientific Applications

• Carboxyl activation: with a tertiary amine base such as DIPEA, NMM or 2,4,6-collidine, PyAOP converts carboxylic acids to reactive OAt esters for amide bond formation.
• Solid-phase and solution-phase peptide synthesis: a high-efficiency activator for Fmoc- and Boc-strategy SPPS and solution-phase peptide coupling.
• Difficult sequences and hindered residues: effective for hindered couplings, including secondary and α,α-disubstituted amino acids, N-methyl residues and difficult short sequences.
• Cyclisation and fragment coupling: used for head-to-tail peptide cyclisation and fragment coupling, where tolerance of excess reagent is useful for slow conversions.
• Low racemisation: the HOAt-derived active ester reduces epimerisation during activation; the weaker base collidine is used for racemisation-prone residues.
• Advantage over uronium and BOP reagents: unlike HATU and related uronium/aminium salts it forms no guanidinylated by-product at the amine, and unlike BOP it generates no HMPA by-product.
• Broader carboxyl and phosphate activation: beyond peptide-chain assembly, PyAOP is a general activator of carboxylic acids and has been reported as an activator of intact trimetaphosphate in triphosphorylation chemistry.

Further Reading

For guidance on selecting between carbodiimides, aminium/uronium salts, phosphonium salts and other reagent classes for amide and peptide bond formation, see NorrChemica's Lab Journal guide: Choosing a Coupling Reagent for Amide and Peptide Bond Formation.