3-hydroxyindole derivatives and synthesis method and use thereof

A technology of hydroxyindole derivatives and synthesis methods, which is applied in the directions of drug combination, organic chemistry, antitumor drugs, etc., can solve the problems of complicated operation, high cost, low cost, etc., and achieves simple and safe operation, high selectivity, high Yield effect

Inactive Publication Date: 2011-05-25
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The present invention overcomes the disadvantages of high cost, low yield and complicated operation in the preparation method of the prior art, and provides a kind of 3-oxindole derivative The synthetic method has the beneficial effects of low cost, high yield, good selectivity and simple operation

Method used

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  • 3-hydroxyindole derivatives and synthesis method and use thereof
  • 3-hydroxyindole derivatives and synthesis method and use thereof
  • 3-hydroxyindole derivatives and synthesis method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Benzyl alcohol (0.4 mmol), nitrogen methyl isatin (0.2 mmol), indium tribromide (14 mg) and 4? molecular sieves (0.1 g) were dissolved in dichloromethane (4 ml), and then Methyl p-methoxyphenyldiazoacetate (0.4mmol, 2.0eq) in dichloromethane (1.0ml) was added dropwise to the reaction system within 1 hour, and the reaction system was refluxed at 40°C. , stirred for 0.5 hours, and the solvent was removed by rotary evaporation under reduced pressure to obtain a crude product. The crude product was subjected to column chromatography (ethyl acetate:petroleum ether=1:20~1:5) to obtain pure product. The yield was 90%, and the dr value was equal to 90:10. The resulting product 3-oxindole derivative ( 8a ), its structural formula is shown in the following formula, and its nuclear magnetic resonance 1 H NMR, 13 C NMR spectrum see figure 1 .

[0059]

Embodiment 2

[0061] Benzyl alcohol (0.4 mmol), 4-chloroazimysatin (0.2 mmol), indium tribromide (14 mg) and 4? molecular sieves (0.1 g) were dissolved in dichloromethane (4 ml), then, Methyl p-methoxyphenyldiazoacetate (0.4mmol, 2.0eq) dissolved in dichloromethane (1.0ml) was added dropwise to the reaction system within 1 hour, and the reaction system was refluxed at 40°C, After the dropwise addition was completed, the mixture was stirred for 0.5 hour, and the solvent was removed by rotary evaporation under reduced pressure to obtain a crude product. The crude product was subjected to column chromatography (ethyl acetate:petroleum ether=1:20~1:5) to obtain pure product. The yield was 84%, and the dr value was equal to 68:32. The resulting product 3-oxindole derivative ( 8b ), its structural formula is shown in the following formula, and its nuclear magnetic resonance 1 H NMR, 13 C NMR spectrum see figure 2 .

[0062]

Embodiment 3

[0064] Benzyl alcohol (0.4 mmol), 5-chloroazimysatin (0.2 mmol), indium tribromide (14 mg) and 4? molecular sieves (0.1 g) were dissolved in dichloromethane (4 ml), then, Methyl p-methoxyphenyldiazoacetate (0.4mmol, 2.0eq) dissolved in dichloromethane (1.0ml) was added dropwise to the reaction system within 1 hour, and the reaction system was refluxed at 40°C, After the dropwise addition was completed, the mixture was stirred for 0.5 hour, and the solvent was removed by rotary evaporation under reduced pressure to obtain a crude product. The crude product was subjected to column chromatography (ethyl acetate:petroleum ether=1:20~1:5) to obtain pure product. The yield was 56%, and the dr value was equal to 62:38. The resulting product 3-oxindole derivative (8c) has a structural formula as shown in the following formula, and its nuclear magnetic resonance 1 H NMR, 13 C NMR spectrum see image 3 .

[0065]

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Abstract

The invention relates to 3-hydroxyindole derivatives, a synthesis method thereof and use thereof. The synthesis method of the 3-hydroxyindole derivatives comprises: dissolving alcohol, an isatin derivative, indiumbromide and a 4-angstrom molecular sieve in an organic solvent, refluxing at 40 DEG C, dripping organic solvent solution of a diazo compound, stirring, removing solvent to obtain a coarse product, and obtaining the 3-hydroxyindole derivatives by column chromatography in solution of ethyl acetate and petroleum ether in a volume ratio of 1:20 to 1:5. In the method, the molar ratio of the diazo compound to the alcohol to the isatin derivative, to the indiumbromide is 2:2:1:0.2, and the added amount per millimol of the 4-angstrom molecular sieve is 4 grams. The synthesis method for preparing the series of 3-hydroxyindole derivatives with diastereoselectivity by one step has the advantages of high atom economy, high selectivity and high yield, the cost of a catalyst is low, and the operation is simple and safe. The 3-hydroxyindole derivatives prepared in the invention has high anticancer activity and can be widely used in medical and chemical fields.

Description

technical field [0001] The invention relates to the field of synthetic medicine and chemical industry, in particular to a 3-hydroxyindole derivative and its synthesis method and application. Background technique [0002] Oxindole derivatives with diastereoselectivity have good anticancer activity and are an important skeleton structure for building natural products and drugs, especially 3-substituted 3-hydroxy-2-oxidized indole derivatives Exist in a large number of biologically active alkaloids, such as TMC-95A, welwitindolinone C, celogentin K, convolutamydines and SM-130686, drugs, antibiotics, antifungals. It can also be used to synthesize many antitumor drugs, antibiotics, and antifungal drugs. The traditional chemical synthesis method of 3-substituted 3-hydroxyl-2-oxidized indole derivatives with diastereomer selectivity is a multi-step synthesis method. The above methods all have high cost, low yield and tedious operation. shortcoming. [0003] The latest method of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/38A61P35/00
Inventor 胡文浩张霞季竟竟周静赵政贾涛
Owner EAST CHINA NORMAL UNIV
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