The synthesis of Tirzepatide mainly adopts the strategy of solid-phase fragment condensation and solid-liquid binding, which focuses on solving the static hindrance effect of unnatural amino acids (such as Aib) in its 39 amino acid long chains, complex modifications of side chains (such as C20 diacid-PEG-γ-Glu-double AEEA-Lys²⁰), and racemic impurity control. The following are specific synthesis methods and technical points:
The synthesis of semaglutide is an extremely complex process because it is a large, chemically modified peptide class (consisting of 31 amino acids). It is not easily done by pure chemical synthesis like small molecule drugs. Its synthesis can relies on a combination of solid-phase peptide synthesis(SPPS) and selective liquid-phase chemical modification. Here's an overview of the key steps of its synthesis route:
The recombinant production of semaglutide is a "semi-recombinant" process that combines genetic engineering fermentation and chemical modification, and the core is to express intermediate peptides through microorganisms, and then enzymatic digestion, chemical modification and purification to obtain the final product. Here are the key process steps and technical points: