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(S)-BIONL derivative CSP filler and preparation method and application thereof

A technology of -BIONL and S-6-ABINOL, which is applied in the field of -BIONL derivative CSP filler and its preparation, can solve problems such as obstacles and inability to separate chiral compounds, and achieve good stability, stable chiral recognition ability, Meet the effect of pharmaceutical analysis and production quality control

Active Publication Date: 2020-01-07
KUNMING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, about 57% of clinically used drugs are chiral drugs, but most of them are used as racemates, and there are less than 100 single enantiomer drugs used clinically
[0004] 1,1'-binaphthol has a C2 symmetry axis and contains two identical naphthalene units. The two naphthalene rings hinder the free rotation of the 1,1'-bond, so BINOL molecules have a stable chiral configuration , but there is still the problem that chiral compounds of various structural types cannot be separated

Method used

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  • (S)-BIONL derivative CSP filler and preparation method and application thereof
  • (S)-BIONL derivative CSP filler and preparation method and application thereof
  • (S)-BIONL derivative CSP filler and preparation method and application thereof

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preparation example Construction

[0041] The present invention also provides a preparation method of the (S)-BIONL derivative CSP filler described in the above technical scheme, comprising the following steps:

[0042] Carry out hydroxyl protection to S-6-A BINOL, obtain the compound with the structure shown in formula II;

[0043]

[0044] Condensing a compound having a structure shown in formula II with a silylating agent to obtain a condensation product;

[0045] The condensation product is bonded to an acidified silica gel carrier, and then subjected to dehydroxylation protection to obtain the (S)-BIONL derivative CSP filler.

[0046] The present invention carries out hydroxyl protection on S-6-A BINOL to obtain a compound having a structure shown in formula II (abbreviated as (S)-1);

[0047]

[0048] The present invention preferably carries out structural modification to the BINOL of S configuration, obtains S-6-acrylic acid BINOL (S-6-A BINOL) at the 6-position substitution acrylic acid of naphth...

Embodiment 1

[0079] This example is to modify the structure of S-configuration BINOL. Substitute acrylic acid at the 6-position of the naphthalene ring to obtain S-6-acrylic acid BINOL (S-6-A BINOL). For 1 and 1 of S-6-A BINOL Carry out hydroxyl protection at the ' position to obtain compound (S)-1, (S)-1 is bonded to the acidified silica gel carrier after silanization, and then removes hydroxyl protection to obtain S-6-acrylic acid BINOL chiral fixed packing (S -6-A BINOL CSP).

[0080] In a 50mL single-necked bottle, dissolve the derivative (S)-1 (1.125mmol, 500mg) in anhydrous dichloromethane (15mL), then add triethylamine (3.375mmol, 0.47mL), and stir in an ice bath After 5 minutes 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate (1.2375 mmol, 470.25 mg) was added. After removing the ice and stirring at room temperature for 30 minutes, 3-aminopropyltriethoxysilane (1.125 mmol, 0.26 mL) was added and reacted at room temperature for 3 hours, and the reaction wa...

Embodiment 2

[0093] This example is to modify the structure of S-configuration BINOL. Substitute acrylic acid at the 6-position of the naphthalene ring to obtain S-6-acrylic acid BINOL (S-6-A BINOL). For 1 and 1 of S-6-A BINOL The hydroxyl group was protected at the ' position to obtain compound (S)-1, and the compound (S)-1 was bonded to an aminopropyl silica gel carrier, and finally dehydroxylated to obtain S-6-A BINOL CSP.

[0094] Take 10g of silica gel, 100mL of 4M hydrochloric acid, N 2 Reflux for 5 hours, cool to room temperature, wash the silica gel with ultrapure water until neutral, and dry it in vacuum at 140°C for 24 hours to obtain acidified silica gel, which is stored in a sealed and cool place for later use. Acidify silica gel (3.5g) and add it into a 250mL three-necked flask filled with 100mL of dry toluene. The toluene takes out the residual moisture and cools to room temperature. According to the specific surface area of ​​silica gel, add 2 times the amount of 3-aminopro...

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Abstract

The invention provides an (S)-BIONL derivative CSP filler and a preparation method and application thereof, belonging to the field of analytical chemistry. The (S)-BIONL derivative CSP filler providedby the invention can be used for separating chiral compounds of various structure types, has good stability and is applicable as a high-performance liquid chromatographic filler. Data of embodimentsindicate that the (S)-BIONL derivative CSP filler provided by the invention can be used for splitting five chiral compounds such as 1,1'-binaphthol, 5-methoxyflavanone, 2'-hydroxyflavanone, thalidomide and N-(3,5-dinitrobenzoyl)-alpha-phenylethylamine under a normal phase condition, has stable chiral recognition ability in a normal-phase chromatography mode, and can meet the requirements of dailydrug analysis and production quality control.

Description

technical field [0001] The invention relates to the technical field of analytical chemistry, in particular to a (S)-BIONL derivative CSP filler and a preparation method and application thereof. Background technique [0002] Chirality is one of the essential attributes of nature on which human beings depend. Biomacromolecules such as proteins, polysaccharides, and nucleic acids all have chirality, and optically active chiral substances widely exist in animals and plants. At present, about 57% of clinically used drugs are chiral drugs, but most of them are used as racemates, and there are less than 100 clinically used single enantiomer drugs. The absorption, distribution, metabolism, excretion and other pharmacokinetic processes of chiral drugs in the body, as well as the mutual recognition and interaction with biomolecules such as proteins, nucleic acids, enzymes, receptors, etc., have certain stereoselectivity, resulting in different enantioselective Because of the differen...

Claims

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Application Information

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IPC IPC(8): B01J20/29B01J20/30B01D15/38G01N30/02
CPCB01D15/3833B01J20/29B01J20/3085G01N30/02G01N2030/027
Inventor 沈报春王永茜杨璨瑜孙孔春
Owner KUNMING MEDICAL UNIVERSITY
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