Hectogram-scale synthesis of [Aib⁸ , Arg³⁴ ]-GLP-1 (7-37) by liquid-phase fragment condensation

Based on small-scale synthesis (0.3 g), a 100-g scale-up synthesis of crude [Aib⁸ , Arg³⁴ ]-glucagon-like peptide-1 (GLP-1) (7-37) was completed. The crude [Aib⁸ , Arg³⁴ ]-GLP-1 (7-37) was purified using a dynamic axial compression column 200 (DAC-200). Approximately 61 g of [Aib⁸ , Arg³⁴ ]-GLP-1 (7-37) with a purity of >99% was obtained through one-step reverse-phase chromatography. The purification yield was approximately 92%. The yield from the total reaction was approximately 60%. In summary, we developed an economical and environmentally friendly route to the synthesis and purification of crude [Aib⁸ , Arg³⁴ ]-GLP-1 (7-37), laying a foundation for subsequent industrial production.