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Indoline isochroman derivative as well as enzymatic synthesis method and application thereof

A technology of heterochromatic and derivatives of indoline, which is applied in the field of fine chemicals, can solve the problems of complicated operation and high production cost, and achieve the effects of simple operation, low production cost and mild reaction

Pending Publication Date: 2021-12-07
浙江理工大学龙港研究院有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Aiming at the problems in the prior art, the present invention provides an indoline isochroman derivative and a preparation method thereof, which solves the shortcomings of the prior art such as complex operation and high production cost, starting from cheap and easy-to-obtain chemical raw materials, through multiple The oxidative coupling reaction catalyzed by copper oxidase is used to obtain high value-added indoline isochroman compounds, and the reaction conditions are mild, the operation is simple, the cost is low, and the environment is green.

Method used

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  • Indoline isochroman derivative as well as enzymatic synthesis method and application thereof
  • Indoline isochroman derivative as well as enzymatic synthesis method and application thereof
  • Indoline isochroman derivative as well as enzymatic synthesis method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Add 2,3-dihydroxybenzoic acid (0.3mmol, 46.2mg), 3-methylindole (0.15mmol, 19.7mg), CotA (0.1mol%), hydrogen peroxide ( 0.75mmol, 75uL), deionized water (1mL), acetonitrile (1mL), hydrochloric acid (0.3mmol, 13uL) magnetically stirred at room temperature for 48 hours, after the conversion of the substrate was completed, ethyl acetate was added to the reaction system for extraction (3mL* 4), the organic phases were combined and dried with anhydrous sodium sulfate, filtered and concentrated in vacuo to obtain a crude product. The obtained crude product was purified and separated by column chromatography to obtain a yellow solid product with an isolated yield of 87%.

[0032] The synthetic route of embodiment 1 is as follows:

[0033]

[0034] figure 1 It is the proton nuclear magnetic resonance spectrum of the target product obtained in Example 1.

[0035] 1 H NMR (400MHz, CDCl 3 ):11.52(s,1H),7.28(s,1H),7.11(q,J=15.6Hz,8.0Hz,2H),6.93(d,J=7.2Hz,1H),6.79(q,J=17.6 ...

Embodiment 2

[0037] Add 2,3-dihydroxybenzoic acid (0.3mmol, 46.2mg), 6-fluoro-3-methylindole (0.15mmol, 22.4mg), CotA (0.1mol% ), hydrogen peroxide (0.75mmol, 75uL), deionized water (1mL), acetonitrile (1mL), hydrochloric acid (0.3mmol, 13uL) were magnetically stirred at room temperature for 48 hours, and ethyl acetate was added to the reaction system after the conversion of the substrate Extract (3mL*4), combine the organic phases and dry over anhydrous sodium sulfate, filter and concentrate in vacuo to obtain the crude product. The obtained crude product was purified and separated by column chromatography to obtain a yellow solid product with an isolated yield of 85%.

[0038] The synthetic route of embodiment 2 is as follows:

[0039]

[0040] The proton nuclear magnetic resonance spectrum of gained target product is as follows:

[0041] 1 H NMR (400MHz, CDCl 3 ):11.50(s,1H),7.30(s,1H),7.08(d,J=8.0Hz,1H),6.85(q,J=5.6Hz,8.8Hz,1H),6.50(d,J=5.2 Hz, 2H), 5.83(s, 1H), 5.08(s, 1H), 1....

Embodiment 3

[0043] Add 2,3-dihydroxybenzoic acid (0.3mmol, 46.2mg), 5-chloro-3-methylindole (0.15mmol, 24.8mg), CotA (0.1mol% ), hydrogen peroxide (0.75mmol, 75uL), deionized water (1mL), acetonitrile (1mL), hydrochloric acid (0.3mmol, 13uL) were magnetically stirred at room temperature for 48 hours, and ethyl acetate was added to the reaction system after the conversion of the substrate Extract (3mL*4), combine the organic phases and dry over anhydrous sodium sulfate, filter and concentrate in vacuo to obtain the crude product. The obtained crude product was purified and separated by column chromatography to obtain a yellow solid product with an isolated yield of 83%.

[0044] The synthetic route of embodiment 3 is as follows:

[0045]

[0046]The proton nuclear magnetic resonance spectrum of gained target product is as follows:

[0047] 1 H NMR (400MHz, CDCl 3 ):11.51(s,1H),7.31(d,J=8.4Hz,1H),7.11–7.08(m,2H),6.88(d,J=2.0Hz,1H),6.71(d,J=8.4Hz ,1H), 5.82(s,1H), 4.99(s,1H), 1.66(s,...

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Abstract

The invention belongs to the technical field of fine chemical synthesis, and particularly relates to an indoline isochroman derivative as well as an enzymatic synthesis method and application thereof. 2,3-dihydroxy benzoic acid and an indole compound are taken as substrates, multi-copper oxidase is taken as a catalyst, and the indoline isochroman derivative is obtained through reaction. The indoline isochroman compound with high added value is obtained from cheap and easily available chemical raw materials through the oxidative coupling reaction catalyzed by using the multi-copper oxidase as the catalyst, and the method is mild in reaction condition, simple to operate, low in cost, green and environmentally friendly.

Description

technical field [0001] The invention belongs to the field of fine chemicals, and in particular relates to an indoline isochroman derivative and an enzyme-catalyzed synthesis method and application thereof. Background technique [0002] Indoline isochroman compounds are a class of monoterpene alkaloids, which widely exist in many natural products and drug molecules, such as bisdophyline and rhynchophylline. Existing studies have proved that they have potential Biological activity, including antibacterial, anti-inflammatory and antitumor effects. In the world of organic chemistry, the synthesis of bispolyphylline is considered a mountain worth climbing. It has been reported in the literature that the synthesis of indoline isochroman compounds often requires the use of transition metals, which has a huge impact on subsequent drug research, especially on the amount of metal residues. Therefore, the traditional chemical synthesis of indoline isochromans is impractical, uneconom...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D491/052C12P17/18
CPCC07D491/052C12P17/188
Inventor 钟芳锐郭欢戴志锋
Owner 浙江理工大学龙港研究院有限公司
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