Method for synthesizing triptorelin from solid phase polypeptide

Abstract

The invention discloses a preparation method of solid phase peptide synthesis triptorelin, which includes the following steps: with Rink Amide AM resins or Rink Amide MBHA resins as starting materials, amino acids with protective groups are sequentially connected according to solid phase synthesis, so as to obtain protective decapeptide resins, and meanwhile crude products are obtained by sequentially removing Fmoc-protective groups and synchronously removing side-chain protective groups and cutting peptides, and triptorelin elaborate products are prepared after the crude products are separated and purified by C18 (or C8 ) column and freeze-dried. The preparation method is stable in technology, convenient in raw and auxiliary material sources, short in production cycle, high in yield, stable in quality, low in production cost and high in transpeptidase yield. Besides, as the preparation method avoids using poisonous reagents, such as hydrogen fluoride, and the like, the pollution of three wastes is low, purification yield is over 25 percent and each step of transpeptidase yield is above 98 percent; the yield after cutting peptides is 78.8 percent and the total yield is 25.4 percent.

Description

technical field [0001] The invention relates to a preparation method of triptorelin, in particular to a preparation method of solid phase polypeptide synthesis triptorelin. Background technique [0002] Chinese name: Triptorelin, Triptorelin Acetate, English name: Triptorelin, Triptorelin Acetate [0003] Structural formula: pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH 2 , molecular formula: C 64 h 82 N 18 o 13 Molecular weight: 1311.5 [0004] Triptorelin is clinically used to treat related sex hormone disorders, including advanced prostate cancer, endometriosis, central precocious puberty, etc. [0005] Triptorelin is a gonadotropin-releasing hormone analogue, which mainly acts on the anterior pituitary gland. In the early stage of high-dose application, it can cause a transient increase in the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and in the later stage it will cause The sensitivity of the pituitary gland is reduced, which red...

AI Technical Summary

Problems solved by technology

[0007] There are certain defects in the current methods. Trifluoroacetic acid must be used for each round of decapping, so the peptide yield is low, resulting in high production costs; there are many wastes, and trifluoroacetic acid is used for purification, which pollutes the environment. The rate is generally below 25%

Therefore current method has limited the large-scale production and use of triptorelin acetate