Method for synthesizing terlipressin by solid-phase oxidization and cyclization

Abstract

The invention discloses a method for synthesizing terlipressin by solid-phase oxidization and cyclization. The method comprises the following steps: (1) obtaining Fmoc-Gly-amino resins by using Fmoc-Gly-OH and amino resins; (2) coupling the Fmoc-Gly-amino resins one by one to obtain linear terlipressin-amino resins; (3) synthesizing the linear terlipressin-amino resins into terlipressin-amino resins by adopting iodine solid-phase oxidized cyclization; (4) cracking and cutting the terlipressin-amino resins to obtain raw peptides of the terlipressin; and (5) carrying out purification, salt conversion and freeze-drying on the raw peptides to obtain terlipressin acetate. The invention has the key innovations that solid-phase oxidization reduces a large amount of waste liquid brought by liquid-phase oxidization, accelerates the reaction time, belongs to process greening reformation and greatly improves the total yield.

Description

technical field

[0001] The invention relates to a method for synthesizing a polypeptide, in particular to a method for synthesizing the polypeptide compound terlipressin by solid-phase oxidation and cyclization. Background technique

[0002] Terlipressin is a new type of artificially synthesized long-acting vasopressin preparation, it is a prodrug, inactive in itself, in the body through the action of aminopeptidase, the 3 glycerols at its N-terminus are removed. After aminoacyl residues, active lysine vasopressin is slowly "released", so terlipressin acts as a depot from which lysine vasopressin is released at a steady rate.

[0003] The molecular formula of terlipressin is: Gly-Gly-Gly-c[Cys-Tyr-Phe-Gln-Asn-Cys]-Pro-Lys-Gly-NH 2

[0004] At present, although there are reports on the synthesis process of terlipressin at home and abroad, most of them are liquid phase synthesis or solid-liquid combination synthesis process. The solid-liquid combination synthesis process ha...

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