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The preparation method of fmoc-d-pro-d-pro-oh

A -bt, -su technology, applied in the field of peptide synthesis, can solve the problems of low product purity, low production efficiency, and high cost, and achieve the effect of low preparation cost, short production steps, and reduced steps

Active Publication Date: 2020-11-10
成都郑源生化科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The problems in the existing methods are: long steps, low yield, low production efficiency, and the product purity is usually not high; or the cost is particularly expensive

Method used

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  • The preparation method of fmoc-d-pro-d-pro-oh
  • The preparation method of fmoc-d-pro-d-pro-oh
  • The preparation method of fmoc-d-pro-d-pro-oh

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Add 43.5g Fmoc-D-Pro-OSu, 100mL ethanol, 0.2mol D-Pro-Na, 3g neodymium selenide NdSe to the reaction flask 2 , stirred at room temperature for 24 hours. Filter, rinse with ethyl acetate, collect the solid, add 200 mL of ethyl acetate, 50 mL of water, acidify with hydrochloric acid to pH ≤ 2, separate the layers; wash the ester layer with 50 mL of saline for 3 times. Concentrate the ester layer to 50mL, add 100mL of n-hexane, crystallize, filter, and dry; 100mL diethyl ether is beaten at 30°C for 3h, filtered, and air-dried at 45°C for 4h; 300mL of water is beaten for 8h, filtered, and air-dried at 45°C to obtain a white solid . The structure is confirmed to be correct by MS and NMR, the product is Fmoc-D-Pro-D-Pro-OH, and its carbon spectrum is shown in the accompanying drawing Figure 1~3 , the total product is 30.5 grams, and the yield is 70.1%. HPLC purity 98.93%, maximum single impurity 0.23%.

Embodiment 2

[0059] Add 100 g of Fmoc-D-Pro-ONB, 200 mL of methanol, 0.4 mol of D-Pro-Na, and 4 g of neodymium selenide into the reaction flask, and stir at room temperature for 24 hours. Filter, collect the solid, add 400ml of ethyl acetate, 100mL of water, acidify with hydrochloric acid to pH ≤ 2, separate the layers; wash the ester layer with 50ml of saline for 3 times. Concentrate the ester layer to 100mL, add 200mL of n-hexane, crystallize, filter, and dry; 200mL diethyl ether is beaten at 30°C for 3h, filtered, and air-dried at 45°C for 4h; 500mL of water is beaten for 8h, filtered, and air-dried at 45°C to obtain a white solid . Compared with the sample obtained in Example 1, it was confirmed that the white solid was Fmoc-D-Pro-D-Pro-OH, the total amount of the product was 63.5 grams, the yield was 73.1%, and the HPLC purity of the product was 98.94%.

Embodiment 3

[0061] Add 91g of Fmoc-D-Pro-OBt, 200mL of methanol, 0.3mol of D-Pro-Na, and 5g of neodymium selenide into the reaction flask, and stir at room temperature for 24 hours. Filter, collect the solid, add 400mL ethyl acetate, 100mL water, acidify with hydrochloric acid to pH ≤ 2, separate the liquids; wash the ester layer 3 times with 50mL brine. Concentrate the ester layer to 100mL, add 200mL of n-hexane, crystallize, filter, and dry; 200mL diethyl ether is beaten at 30°C for 3h, filtered, and air-dried at 45°C for 4h; 500mL of water is beaten for 8h, filtered, and air-dried at 45°C to obtain a white solid . Compared with the sample obtained in Example 1, it was confirmed that the white solid was Fmoc-D-Pro-D-Pro-OH, the total amount of the product was 60.5 grams, the yield was 69.7%, and the HPLC purity was 98.92%.

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Abstract

The invention discloses a preparation method of Fmoc-D-Pro-D-Pro-OH and belongs to the field of polypeptide synthesis. The preparation method of Fmoc-D-Pro-D-Pro-OH comprises the following steps thata, Fmoc-D-Pro-OR, D-Pro-Na, NdSe2 and a solvent are mixed and react to obtain Fmoc-D-Pro-D-Pro-ONa, wherein the Fmoc-D-Pro-OR can react with esters of amide bonds; b, the Fmoc-D-Pro-D-Pro-ONa is acidified to obtain the Fmoc-D-Pro-D-Pro-OH. The Fmoc-D-Pro-D-Pro-OH prepared through the method is shorter in production step, high in main reaction speed and easier to purify, fewer byproducts are generated, the production efficiency is improved, and the method is suitable for industrial production.

Description

technical field [0001] The preparation method of Fmoc-D-Pro-D-Pro-OH of the present invention belongs to the field of polypeptide synthesis. Background technique [0002] Fmoc-D-Pro-D-Pro-OH is fluorenylmethoxycarbonyl-D-prolyl-D-proline, which is a chemical intermediate, often used in peptide synthesis or as a quality control standard for peptide synthesis raw materials . [0003] In the prior art, there are two common methods for preparing Fmoc-D-Pro-D-Pro-OH. [0004] One is the liquid phase synthesis method: first react to generate Fmoc-D-Pro-OR activated ester, then react with D-Pro-OR′, connect peptide to generate Fmoc-D-Pro-D-Pro-OR′, and then saponify to generate D-Pro-D-Pro, and then add Fmoc protecting group to generate Fmoc-D-Pro-D-Pro-OH. However, this method has long steps, and the preparation process needs to remove the Fmoc group first, and then add the Fmoc group, which increases the consumption of Fmoc reagents and increases the cost. [0005] The other ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/078C07K1/06
CPCC07K5/06165
Inventor 杨再宽郑征韩祥
Owner 成都郑源生化科技有限公司