Yi Yang
Chemical Development, Global Pharmaceutical R&D, Ferring Pharmaceuticals A/S, Denmark
Yi Yang
Chapters authored
Green Chemistry of Minimal-Protection Solid-Phase Peptide Synthesis
The conventional SPPS (solid-phase peptide synthesis) requires protecting the nucleophilic side chains of amino acids to prevent undesired modifications. A large volume of TFA (trifluoroacetic acid) is generally needed to remove these protecting groups post the peptide assembly. Such a process significantly lowers the productivity of the subject peptide manufacturing and is deemed contradictory to green chemistry concepts. Enabling the side-chain unprotected amino acid couplings should break through such a bottleneck in peptide production and drastically increase productivity. This aspiration creates the concept of MP-SPPS (Minimal-Protection Solid-Phase Peptide Synthesis), accomplished in peptide API (Peptide Z) manufacturing. Side-chain unprotected arginine and tyrosine have been successfully incorporated into the target peptide chain on solid supports. The target peptide Z could be readily obtained by treating the peptidyl resin with a diluted acid solution, that is, 10% TFA/TFT (trifluorotoluene), and precipitating the solid product in a radically reduced volume of anti-solvent. The MP-SPPS process achieves a 5.3-fold increase in peptide Z manufacturing and complies with the philosophy of green chemistry.
Part of the book: Advances in Green Chemistry