Synthesis method of goserelin

Abstract

The invention provides a synthesis method of goserelin. The synthesis method comprises the following steps: generating pGlu-His (Trt)-Trp (Boc)-Ser (tBu)-Tyr (tBu)-OH and Fmoc-D-Ser (tBu)-Leu-Arg (NO2)-Pro-OH by virtue of a solid-phase synthesis method; carrying out Fmoc removal on the generated Fmoc-D-Ser (tBu)-Leu-Arg (NO2)-Pro-OH, so as to generate NH2-D-Ser (tBu)-Leu-Arg (NO2)-Pro-AzaGly-NH2; carrying out liquid phase coupling on two fragments, namely pGlu-His (Trt)-Trp (Boc)-Ser (tBu)-Tyr (tBu)-OH and NH2-D-Ser (tBu)-Leu-Arg (NO2)-Pro-AzaGly-NH2, and then removing an-NO2 protecting group, so as to obtain a goserelin crude product; and preparing a refined goserelin product through RP-HPLC (Reverse Phase-High Performance Liquid Chromatography) purification and freeze-drying. The method has the beneficial effects that the problem that the synthesis yield is low when a conventional Fmoc / tBu solid-phase reaction system is adopted is solved, the production period is shortened, the method is more suitable for large-scale production. Meanwhile, the production cost is also greatly reduced.

Description

technical field [0001] The invention belongs to the chemical synthesis of medical polypeptide raw materials, and specifically relates to a synthesis method of goserelin. Background technique [0002] Goserelin, also known as goserelin, goserelin, goserelin, goserelin, etc., is a synthetic decapeptide compound with an amino acid sequence of pGlu-His-Trp-Ser-Tyr-D- Ser(tBu)-Leu-Arg-Pro-AzaGly-NH 2 . It is a structural analogue of luteinizing hormone-releasing hormone (GnRH). The difference from natural GnRH is that it can promote the release of gonadal hormones on the 6th and 10th groups of the peptide chain, and its effect is 50 times stronger than that of GnRH secreted by the human body. ~100 times, LHRH analogues can feedback inhibit the secretion of LH and FSH by competing for most receptors of pituitary LHRH, thereby inhibiting the production of ovarian estrogen and achieving the therapeutic effect of drug-induced ovariectomy. For male patients, the concentration of se...

AI Technical Summary

Problems solved by technology

The operation of liquid-phase synthesis is cumbersome, each synthesis step needs to be purified, and the synthesis yield is very low. It is not suitable for the synthesis of peptides with more than 5 amino acids. The price of raw materials for liquid-phase synthesis is much higher than that of Fmoc / tBu solid produced in large-scale industrial production The price of raw materials in the phase system directly affects the production cost; for solid-phase synthesis methods, SPPS in peptide synthesis is generally used for the total synthesis of the entire sequence. However, goserelin contains tBu and conventional The Fmoc / tBu solid-phase reaction system is incompatible, and the conventional Fmoc / tBu solid-phase reaction system cannot be synthesized or the yield is very low, which is not suitable for large-scale production

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