New synthesis method of important biochemical reagent L-leucine-4-nitroaniline hydrochloride

A technology of nitroaniline and biochemical reagents, applied in the field of synthesis of fluorescent peptidase substrates, can solve the problems of low direct condensation yield, non-reaction or low yield, high cost, etc. Easy-to-obtain, simple-to-operate effects

Active Publication Date: 2013-02-20
SUZHOU BAILINGWEI HYPERFINE MATERIAL
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Problems solved by technology

[0004] But now it is known that there are many methods for preparing the key intermediate Boc-L-leucine-4-nitroaniline (Boc-L-Leu-pNA). Condensation reagents such as DCC, DCC/HOBt, or acid anhydride method for direct condensation yields are very low (0-30%)
Document 1: (Shioiri, Takayuki; Murata, Mitsuo; Hamada, Yasumasa; Chemical and Pharmaceutical Bulletin; 1987; 35(7); 2698-2704) used a seri

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  • New synthesis method of important biochemical reagent L-leucine-4-nitroaniline hydrochloride
  • New synthesis method of important biochemical reagent L-leucine-4-nitroaniline hydrochloride
  • New synthesis method of important biochemical reagent L-leucine-4-nitroaniline hydrochloride

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Embodiment 1

[0028] The first step reaction: preparation of intermediate 3

[0029] Add compound 2 (12.2g, 93.1mmol, 1eq), dioxane / water (60mL / 60mL) into a 500mL four-necked flask under magnetic stirring, and configure 165mL aqueous solution of sodium hydroxide (7.5g, 210.4mmol, 2eq) , the solution was slowly added to the bottle, the temperature did not change significantly, after the solid was completely dissolved, under an ice-water bath, a mixed solution of BOC anhydride (42.6g, 210.4mmol, 2.26eq) and dioxane (42mL) was added dropwise. After dropping, the reaction was continued at room temperature. After TLC monitors the complete reaction of raw materials, it is adjusted to acidity with dilute hydrochloric acid. The reaction solution was extracted with ethyl acetate (200 mL*3). The organic phase was washed three times with saturated sodium chloride solution (100 mL*3), dried over sodium sulfate, and concentrated under reduced pressure to obtain 21.8 g of intermediate 3, a colorless vi...

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Abstract

The invention relates to a new synthesis method of an important biochemical reagent L-leucine-4-nitroaniline hydrochloride. The method includes: under the action of sodium hydroxide, reacting an L-Leu-OH solution with BOC anhydride to obtain Boc-L-Leu-OH; subjecting the Boc-L-Leu-OH and a pyridine solution of p-nitroaniline to condensation under the action of phosphorus oxychloride so as to generate the key intermediate Boc-L-Leu-pNA, with the condensation method being novel and not reported in the literature; and reacting a glacial acetic acid solution of the Boc-L-Leu-pNA with a hydrogen chloride gas so as to generate Boc-L-leucine-4-nitroaniline hydrochloride. The method has the advantages of easily available starting raw materials, short reaction steps, convenient operation, high yield, and low cost.

Description

technical field [0001] The invention belongs to the field of biochemical reagent amino acid p-nitroaniline, in particular to a new method for synthesizing fluorescent peptidase substrates. Background technique: [0002] The amino acid p-nitroaniline is a valuable and widely used chromogenic substrate for the determination of proteolytic enzyme activity in body fluids; L-leucine-4-nitroaniline is a substrate for leucine aminopeptidase; In addition, L-leucine-4-nitroaniline hydrochloride can also be used as an intermediate of diazo dyes and sulfur dyes (such as oxaprop-methyl, fluorescent whitening agent KCB). However, since p-nitroaniline is a very weak nucleophile, the synthesis of such compounds is very difficult and the yield is very low. [0003] [0004] But now it is known that there are many methods for preparing the key intermediate Boc-L-leucine-4-nitroaniline (Boc-L-Leu-pNA). Condensation reagents such as DCC, DCC / HOBt, or the anhydride method carry out direct ...

Claims

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Application Information

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IPC IPC(8): C07C237/04C07C231/12
Inventor 宋绍兴邹增龙顾扬
Owner SUZHOU BAILINGWEI HYPERFINE MATERIAL
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