Azacyclopropene compound, and preparation method and application thereof

A technology of compounds and nitrogen heterocycles, applied in the field of molecular probes in chemical biology, can solve the problem of selective modification research but few

Active Publication Date: 2020-10-23
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, the most extensive selective modification is the small molecule research based on the modification of cyst...

Method used

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  • Azacyclopropene compound, and preparation method and application thereof
  • Azacyclopropene compound, and preparation method and application thereof
  • Azacyclopropene compound, and preparation method and application thereof

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preparation example Construction

[0087] Compound preparation

[0088] In addition to standard methods known in the literature or exemplified in experimental procedures, the compounds of the invention can be prepared using the methods shown in the following synthetic schemes. Combined with the following synthesis scheme, the compounds and synthesis methods described in the present invention can be better understood. The synthetic schemes describe methods that can be used to prepare the compounds described in the present invention, and the methods described are illustrative scheme descriptions for illustrative purposes only and are not intended to limit the scope of the invention.

[0089]

[0090] Synthetic Scheme 1

[0091]

[0092] Synthetic Scheme 2

[0093] Compound application

[0094] The present invention also provides the application of the above-mentioned aziridine compound. The compound of formula I provided by the present invention has the effect of labeling the amino acid residues of prot...

Embodiment 1

[0104]

[0105] In the first step, compound 1 (8 mL, 48.2 mmol) was dissolved in dry THF (5 mL), LDA (6.58 mL, 53.1 mmol) was added under argon protection at -15°C, and reacted at 0°C for 30 minutes. Then 3-bromopropyne (4.24 mL, 53.1 mmol) was added and reacted at room temperature for 12 h. with saturated NH 4 The Cl solution was quenched and extracted with ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and compound 2 (8.32 g, 88%) was obtained by silica gel column chromatography. 1 H NMR (400MHz, CDCl 3 )δ3.36(s,2H),2.85–2.73(m,2H),2.50–2.42(m,2H),1.96–1.94(m,1H),1.46(s,12H).

[0106] In the second step, compound 2 (3.0g, 15.2mmol) was added to NH 2 OH·HCl (1.17g, 16.72mmol) in pyridine (10mL) was reacted at 50°C for 24h, the solvent was removed under reduced pressure, diluted with water and extracted with ethyl acetate. The organic layers were combined and ...

Embodiment 2

[0109]

[0110] In the first step, compound 4 (8mL, 48.2mmol) was dissolved in dry THF (5mL), sodium hydride (1.95g, 48.7mmol) was added under the protection of argon at 0°C, and reacted at 0°C for 30 minutes. Then 3-bromopropyne (4.24 mL, 53.1 mmol) was added and reacted at room temperature for 12 h. with saturated NH 4 The Cl solution was quenched and extracted with ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and compound 5 (7.57 g, 80%) was obtained by silica gel column chromatography. 1 H NMR (400MHz, CDCl 3 )δ3.56(t, J=7.5Hz, 1H), 2.63(dt, J=7.6, 2.2Hz, 2H), 2.26(s, 3H), 1.96(t, J=2.7Hz, 1H), 1.44( s,9H).

[0111] The synthesis of compound 6 refers to the synthesis of compound 3 in Example 1.

[0112] Synthesis of Compound Az-2 Reference Example 1 Synthesis of Compound Az-1, yield 40%. 1 H NMR (400MHz, CDCl 3 )δ3.14(dd, J=18.3,2.7Hz,1H),2.71(dd,J=18....

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Abstract

The invention relates to an azacyclopropene compound with a structure as shown in a formula I, and a preparation method and application thereof. The azacyclopropene compound has high selectivity and high efficiency in labeling (modifying) protein amino acid residues, can selectively modify acidic amino acid residues, has a good labeling effect, can be used for researching the activity of proteins,and is crucial to chemical proteomics application and development of covalent inhibitors.

Description

technical field [0001] The invention relates to the technical field of chemical biology molecular probes, in particular to an aziridine compound and its preparation method and application. Background technique [0002] Covalent modification of proteins using chemical tools is a powerful approach to identify, quantify, and modulate these protein biomolecules. Small molecular compounds are powerful tools for studying protein functions. They can regulate protein functions by forming covalent bonds, and provide benefits for the treatment of some diseases, such as enhancing and sustaining the inhibitory effect of drugs. However, most human proteins are not ready for drug design due to the lack of small molecule ligands. Selective modification of specific protein sites is one of the effective ways to solve the above problems. At present, the most extensive selective modification is the small molecule research based on the modification of cysteine ​​and lysine residues, and aspar...

Claims

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Application Information

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IPC IPC(8): C07D203/04C07K1/13
CPCC07D203/04C07K1/13Y02P20/55
Inventor 李正球麻楠叶文才丁克胡俊
Owner JINAN UNIVERSITY
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