PyBOP | CAS 128625-52-5 | ≥98%

Fmoc and Boc solid-phase peptide synthesis — PyBOP is the standard phosphonium coupling reagent for both Fmoc- and Boc-based SPPS, providing coupling efficiency equivalent to BOP without generating the carcinogenic by-product HMPA. In the activation step, PyBOP reacts with the carboxylic acid of the incoming protected amino acid in the presence of a tertiary amine base (DIPEA or NMM) to form a benzotriazolyl active ester intermediate, which then aminolyses the resin-bound free amine to form the peptide bond. The tripyrrolidinophosphine oxide (TPPO) by-product is non-carcinogenic and easily removed during standard washing cycles. PyBOP was introduced by Coste, Le-Nguyen, and Castro (Tetrahedron Lett. 1990, 31, 205) and has since become one of the most widely used coupling reagents in both academic and industrial peptide synthesis.

Fragment condensation without guanidination — the most important advantage of PyBOP over uronium/aminium reagents (HBTU, HATU, HCTU) is the absence of guanidination side reactions. When uronium reagents are used in excess, the tetramethylguanidinium cation can react directly with free amino groups on the peptide, irreversibly capping the N-terminus and terminating chain elongation. Because PyBOP carries a phosphonium cation instead of a guanidinium, this capping reaction is structurally impossible. This makes PyBOP the reagent of choice for convergent peptide synthesis and any protocol where the coupling reagent cannot be precisely controlled stoichiometrically.

Head-to-tail macrolactamisation and cyclic peptides — PyBOP is a preferred reagent for intramolecular cyclisation of linear peptide precursors. In cyclisation reactions the coupling reagent is typically used in significant excess to drive the entropically disfavoured ring closure to completion. The guanidination-free profile ensures the free N-terminus remains available throughout the reaction. Høeg-Jensen et al. (Tetrahedron Lett. 1991, 32, 7617) demonstrated PyBOP’s effectiveness in macrolactam formation.

Safe BOP replacement — elimination of HMPA — BOP (Castro’s reagent, 1975) was one of the first high-performance phosphonium coupling reagents but generates one equivalent of hexamethylphosphoramide (HMPA) per coupling cycle. HMPA is classified as a Category 1B carcinogen (H350) under CLP, making BOP unsuitable for industrial-scale peptide manufacturing. PyBOP was specifically designed to solve this problem — the three pyrrolidine rings replace the three dimethylamino groups of BOP, yielding TPPO instead of HMPA while preserving identical coupling kinetics and stereochemical fidelity.

Esterification, conjugation, and specialty applications — beyond amide bond formation, PyBOP activates carboxylic acids for esterification with alcohols, useful in the preparation of structured triacylglycerols with defined regiochemistry for lipid research (von Eggelkraut-Gottanka et al., Tetrahedron Lett. 2003, 44, 3551). PyBOP has also been employed in peptide-oligonucleotide conjugate preparation and solid-phase synthesis of 3,5-pyrazolidinediones on soluble PEG supports, demonstrating versatility beyond conventional peptide chemistry.