Liquid-phase synthesis method of thymopentin based on phosphorus or phosphorousoxy diphenylmethanol and derivatives and auxiliary groups

Abstract

The invention relates to a liquid-phase synthesis method of thymopentin (TP-5) based on polyarylphosphorus or phosphoroxyphenylcarbinol (POB) compounds and their derivatives and auxiliary groups, comprising the following steps: a phosphorus or phosphite carrier replaces solid phase resin to be connected with the C- end of Fmoc-protected tyrosine under the action of a coupling dehydrant; N-end Fmocis removed after separation and purification; coupling with Fmoc, valine with side chain protection, asparaginic acid, lysine and arginine and Fmoc removal reaction are carried out to prepare a precursor C of thymopentin; and side chain is deprotected and the carrier is cleaved to obtain a solid of thymopentin. Compared with existing synthetic methods, the synthesis method of the invention has the advantages of liquid-phase and solid-phase synthesis, and can be adopted for simpler, faster, economical, efficient and large-scale synthesis of thymopentin. The POB auxiliary groups can be recovered and directly reused, raw material waste is reduced, waste pollution is lowered, costs are saved, and the method is good for environmental protection.

Description

technical field [0001] The invention belongs to the synthesis method of polypeptide in the field of bioorganic chemistry, and relates to a liquid-phase synthesis method of thymopentin based on phosphorus or phosphorous oxybenzhydrin alcohol and its derivatives and assistants. Background technique [0002] Thymus hormones are a family of polypeptide protein hormones secreted by the thymus. These hormones play a crucial role in individual development and regulation of immune system function. Thymopoientin (TP) is one of the hormones secreted by thymus epithelial cells. It is a 49-amino acid polypeptide isolated from human thymus tissue. It can promote the differentiation and development of thymocytes and peripheral T cells and B cells. Regulate the body's immune function and other biological activities, see literature: Jiang Dingwen, Li Chufang, Foreign Medicine: Biological Products for Prevention, Diagnosis, and Therapy, 1999, 2(2): 69-72. It was isolated from bovine thymus ...

AI Technical Summary

Problems solved by technology

1. Biotechnology method: Although the research on the production of TP-5 by biotechnology is very active, the main problem is that on the one hand, the technology is relatively complicated and immature, and it is restricted by factors such as raw materials; on the other hand, due to The reason of the raw material may also cause the pollution of the product, it is difficult to produce on a large scale, and the development prospect is very bleak

However, the existing problem is that the intermediate product must be separated and purified with acetonitrile after each step of the reaction in the synthesis process, which requires a large amount of use and high cost: multiple cycles of purification and recrystallization processes take a long time; the high risk of HF makes it difficult to Peptide cleavage and protective group removal need to be completed in a special device, which makes the process and equipment complicated

[0013] In short, the current chemical synthesis method of thymopentin (TP-5) is relatively complicated in liquid phase reaction, with many separation steps, long time-consuming cycle, small purification scale and high production cost, while the production scale of solid phase reaction is small and the price of raw materials is expensive. , waste, resin waste and serious environmental pollution problems

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