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Overcoming the "Choke Points" in Semaglutide Side Chain Synthesis with Core Technologies to Enable Efficient GLP-1 Drug Manufacturing
Semaglutide, a groundbreaking product in the GLP-1 drug class, owes its extended half-life and enhanced receptor affinity largely to its unique side chain, Ste-Glu-AEEA-AEEA-OSU (CAS: 1169630-40-3) . This side chain covalently modifies the peptide backbone, significantly improving pharmacokinetics and therapeutic performance. However, its complex structure presents two critical synthetic challenges: Precise Assembly of Repetitive AEEA Units: The side chain features consecutive AEEA (aminoethoxyethoxyacetic acid) units, which require stepwise coupling via highly activated intermediates (e.g., AEEA-AEEA). Any impurities or deviations compromise downstream reaction efficiency and may trigger irreversible byproducts. Stereochemistry and Stability of Glutamic Acid (Glu): The glutamic acid component must maintain strict L-configuration, and its carboxyl groups require directional protection (e.g., OtBu) to preserve biological activity. Leveraging deep expertise in peptide chemistry a...
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