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Total Synthesis of Semaglutide Based on a Soluble Hydrophobic-Support-Assisted Liquid-Phase Synthetic Method
Xingbang Liu1, Na Zhang1, Xiaotong Gu1
1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China.
Abstract:
Considering the high cost of the production of semaglutide, which is currently the most promising antidiabetic drug especially for the treatment of type 2 diabetes mellitus, a new synthetic route of semaglutide production that possesses excellent yield and high purity is of vital importance. Herein, we reported a newly developed synthetic route of semaglutide that is simple and efficient, based on a soluble hydrophobic-support-assisted liquid-phase synthetic method by applying Alloc-chemistry to the synthesis of the main chain peptide and side chain peptide of semaglutide. With careful optimization of the reaction conditions and innovative strategy of post-synthetic treatments, the total yield and purity of the crude semaglutide was improved satisfactorily.
