Method for preparing carperitide acetate

The technology of caperitide and acetic acid is applied in the field of preparation of caperitide acetate, which can solve the problems of no solid-phase synthesis process method, etc., and achieve the effects of considerable economical and practical value, easy post-processing and less input of raw materials

Active Publication Date: 2012-03-21
HYBIO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, there is a domestic patent for capecritide (patent number: ZL200510012425.5), which is produced by genetic recombination technology, and there is no report on the solid-phase synthesis process; the CA1245635A1 patent reports that the Boc route is used to synthesize capecritide. The CA1245637A1 patent repo

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Embodiment 1, the synthesis of Fmoc-Tyr (tBu)-Wang Resin

[0049] Add 4.8 grams of Wang Resin (sub=0.5mmol / g) to a 50ml reaction column, add DMF to swell for 30 minutes, and wash the resin three times with an appropriate amount of DMF. Weigh Fmoc-Tyr(tBu)-OH (2.89g, 6.3mmol), HOBT (1.02g, 7.56mmol), mix them all, add DMF (10ml), DCM (10ml) and stir to dissolve completely. Then DIC (0.98ml, 6.3mmol) was added and stirred at room temperature for 20min. The reaction solution was transferred to a reaction column, and DMAP (29.3mg, 0.24mmol) was added, and reacted for 3h with nitrogen blowing. Drain the reaction solution and wash the resin 4 times with DMF, then add acetic anhydride (16.2ml, 180mmol), pyridine ((13.8ml, 180mmol) and react for 2h. Drain the reaction solution and wash the resin 6 times with DMF. Vacuum dry, Sampling and measuring its degree of substitution is 0.3mmol / g.

Embodiment 2

[0050] Embodiment 2, the synthesis of Fmoc-Tyr (tBu)-Wang Resin

[0051]Add 3.0 grams of Wang Resin (sub=0.8mmol / g) to a 50ml reaction column, add DMF to swell for 30 minutes, and wash the resin three times with an appropriate amount of DMF. Weigh Fmoc-Tyr(tBu)-OH (2.89g, 6.3mmol), HOBT (1.02g, 7.56mmol), mix them all, add DMF (10ml), DCM (10ml) and stir to dissolve completely. Then DIC (0.98ml, 6.3mmol) was added and stirred at room temperature for 20min. The reaction solution was transferred to a reaction column, and DMAP (29.3mg, 0.24mmol) was added, and reacted for 3h with nitrogen blowing. Drain the reaction solution and wash the resin 4 times with DMF, then add acetic anhydride (16.2ml, 180mmol), pyridine ((13.8ml, 180mmol) and react for 2h. Drain the reaction solution and wash the resin 6 times with DMF. Vacuum dry, Sampling and measuring its degree of substitution is 0.4mmol / g.

Embodiment 3

[0052] Embodiment 3, the synthesis of Fmoc-Tyr (tBu)-Wang Resin

[0053] Add 2.4 grams of Wang Resin (sub=1.0mmol / g) to a 50ml reaction column, add DMF to swell for 30 minutes, and wash the resin three times with an appropriate amount of DMF. Weigh Fmoc-Tyr(tBu)-OH (2.89g, 6.3mmol), HOBT (1.02g, 7.56mmol), mix them all, add DMF (10ml), DCM (10ml) and stir to dissolve completely. Then DIC (0.98ml, 6.3mmol) was added and stirred at room temperature for 20min. The reaction solution was transferred to a reaction column, and DMAP (29.3mg, 0.24mmol) was added, and reacted for 3h with nitrogen blowing. Drain the reaction solution and wash the resin 4 times with DMF, then add acetic anhydride (16.2ml, 180mmol), pyridine ((13.8ml, 180mmol) and react for 2h. Drain the reaction solution and wash the resin 6 times with DMF. Vacuum dry, Sampling and measuring its degree of substitution is 0.6mmol / g.

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PUM

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Abstract

The invention discloses a method for preparing carperitide acetate. The method comprises the following steps of: 1) reacting Fmoc-Tyr(tBu)-OH with WangResin with the substitution value of 0.5-1.0mmol/g to obtain Fmoc-Tyr(tBu)-WangResin; 2) synthesizing the Fmoc-Tyr(tBu)-WangResin by adopting a mode of coupling one by one to obtain linear carperitide-WangResin; 3) oxidizing the carperitide-WangResin by using a solid-phase oxidation method; 4) cracking by using trifluoroacetic acid to obtain crude carperitide; and 5) purifying the crude carperitide by using reversed phase high performance liquid chromatography to obtain high-purity refined carperitide. The process has the advantages of simple reaction and operation, simple posttreatment, high yield, low cost and the like.

Description

technical field [0001] The invention relates to a preparation method of a polypeptide, in particular to a preparation method of capecritide acetate. Background technique [0002] Caperitide contained in this product is also known as recombinant atrial peptide, caperidine, Hamp, and human brain natriuretic peptide. Its indications are acute heart failure (including exacerbation of chronic heart failure). The pharmacological effect of capecritide is to stimulate myocardial stretching, synthesized by intraventricular particles, and then distributed throughout the body through coronary arteries, acting on vascular smooth muscle and kidney and other tissues to regulate blood pressure and electrolyte balance in the body. This product is a circulation regulating hormone composed of 28 amino acids, which acts as a vasodilator and diuretic. The vasodilation caused by this product is due to the combination with the ANP (atrial natriuretic polypeptide) receptor of vascular smooth mus...

Claims

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Application Information

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IPC IPC(8): C07K14/58C07K1/20C07K1/06C07K1/04
Inventor 张文治付信刘建马亚平袁建成
Owner HYBIO PHARMA
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