A kind of chiral gamma-butyrolactone derivative and its synthesis method and application

A technology for butyrolactone and derivatives, applied in the field of optically active γ-butyrolactone derivatives and their synthesis, can solve the problems of many steps in the synthesis process, unstable raw materials, inconvenient operation, etc., and achieve fewer reaction steps and better Anti-cancer effect with low cost

Active Publication Date: 2022-03-08
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

There are many shortcomings in the synthesis of many optically active γ-butyrolactone derivatives reported today, most of which are harsh conditions, or the raw materials used are unstable or difficult to obtain, the synthesis process has many steps, the yield is low, and the operation is extremely inconvenient

Method used

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  • A kind of chiral gamma-butyrolactone derivative and its synthesis method and application
  • A kind of chiral gamma-butyrolactone derivative and its synthesis method and application
  • A kind of chiral gamma-butyrolactone derivative and its synthesis method and application

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Experimental program
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Effect test

Embodiment 1

[0055] The preparation of embodiment 1 compound 3b1

[0056]

[0057] Rh 2 (esp) 2 (0.008mmol), chiral phosphoric acid (0.02mmol), 3-p-bromophenylcyclopropene carboxylic acid (0.36mmol), and p-bromobenzylideneaniline (0.2mmol) were dissolved in a test tube containing 2.5mL tetrahydrofuran, and Stir at a specific temperature (25° C.) and react for 96 hours. After the imine reaction is complete, the solvent is removed by rotary evaporation under reduced pressure to obtain a crude product. The crude product was subjected to column chromatography (ethyl acetate:petroleum ether=1:10-1:3) to obtain a pure product. Yield 91%, dr>95:5, er:93:7.

[0058] 1 H NMR (500MHz, CDCl 3 )δ7.65–7.61(m,2H),7.55–7.49(m,4H),7.38–7.33(m,3H),7.12–7.06(m,2H),6.73(dd,J 1 =J 2 =7.4Hz,1H),6.55–6.50(m,2H),5.19(dd,J=6.4,1.8Hz,1H),5.19(dd,J=6.4,1.8Hz,1H),4.53(d,J= 6.1Hz, 1H), 4.53(d, J=6.1Hz, 1H), 4.49(s, 1H), 4.49(s, 1H). 13 C NMR (125MHz, CDCl 3 )δ170.6,146.2,144.9,137.5,132.4,132.1,132.0,129...

Embodiment 2

[0059] The preparation of embodiment 2 compound 3aq

[0060]

[0061] Rh 2 (esp) 2 (0.008mmol), chiral phosphoric acid (0.02mmol), 3-phenylcyclopropene carboxylic acid (0.36mmol), and p-fluorobenzylidene p-chloroaniline (0.2mmol) were dissolved in a test tube containing 2.5mL tetrahydrofuran, and Stir at a specific temperature (25° C.) and react for 96 hours. After the imine reaction is complete, the solvent is removed by rotary evaporation under reduced pressure to obtain a crude product. The crude product was subjected to column chromatography (ethyl acetate:petroleum ether=1:10-1:3) to obtain a pure product. Yield 80%, dr: 94:6, er: 95:5.

[0062] 1 H NMR (500MHz, CDCl 3 )δ7.76(dd,J 1 =J 2 =6.6,3.0Hz,2H),7.46–7.37(m,5H),7.32(d,J=1.8Hz,1H),7.10(dd,J 1 =J 2 =8.5Hz,2H),7.05–7.01(m,2H),6.47–6.42(m,2H),5.17(dd,J=6.9,1.7Hz,1H),4.57(d,J=3.9Hz,1H) ,4.46(dd,J=6.8,4.2Hz,1H). 13 C NMR (125MHz, CDCl 3 )δ170.8, 162.7 (d, J = 247.9Hz), 144.9, 144.4, 133.8 (d, J = 3.2Hz), 1...

Embodiment 3

[0063] The preparation of embodiment 3 compound 3a1

[0064]

[0065] Rh 2 (esp) 2 (0.008mmol), chiral phosphoric acid (0.02mmol), 3-phenylcyclopropene carboxylic acid (0.36mmol), benzylidene p-bromoaniline (0.2mmol) were dissolved in a test tube containing 2.5mL tetrahydrofuran, at a specific temperature Stir at (25° C.) and react for 96 hours. After the imine reaction is complete, the solvent is removed by rotary evaporation under reduced pressure to obtain a crude product. The crude product was subjected to column chromatography (ethyl acetate:petroleum ether=1:10-1:3) to obtain a pure product. Yield 89%, dr:95:5, er:94.5:5.5.

[0066] 1 H NMR (400MHz, CDCl 3 )δ7.75(dd,J 1 =J 2 =6.4,2.7Hz,2H),7.49–7.28(m,9H),7.15(d,J=8.7Hz,2H),6.41(d,J=8.7Hz,2H),5.19(dd,J=7.1, 1.2Hz, 1H), 4.61(d, J=3.5Hz, 1H), 4.44(dd, J=6.9, 4.1Hz, 1H). 13 C NMR (100MHz, CDCl 3 )δ170.9,145.6,144.8,138.0,133.0,131.9,129.7,129.3,129.1,128.8,127.21,127.15,116.0,110.6,83.0,61.9.HRMS(ESI)m / z:calcd....

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Abstract

The invention discloses a chiral γ-butyrolactone derivative, a synthesis method and application thereof. Its structure is shown in formula (1); wherein, Ar 1 、Ar 2 and Ar 3 Each independently is phenyl, halogenated phenyl, nitro-substituted phenyl, C 1～4 Alkyl substituted phenyl, C 1～4 Alkoxy substituted phenyl, C 1～4 Haloalkyl is substituted for phenyl, naphthyl or halonaphthyl. The derivatives described in the present invention have a novel structure, and have good anti-cancer effects, especially for human breast cancer cells (MCF-7) and human lung adenocarcinoma cells (A549), and have good inhibitory effects, It exhibits good anti-breast cancer and lung cancer cell effects, and can be prepared as an anti-breast cancer and lung cancer drug for application; in addition, the preparation method of the compound is simple, using cheap and easy-to-obtain compounds as raw materials, and has mild reaction conditions, The invention has beneficial effects such as few reaction steps, fast reaction, less waste generated, simple and safe operation, high atom economy, high selectivity, and high yield.

Description

technical field [0001] The invention belongs to the fields of synthetic medicine and chemical industry, and mainly relates to an optically active gamma-butyrolactone derivative and its synthesis method and application. Background technique [0002] γ-butyrolactone is the basic skeleton of many natural products, more than 10% of natural compound molecules contain γ-butyrolactone structure, and is widely used in various fields, such as materials, agriculture, biology, medicine and so on. Optically active γ-butyrolactone derivatives have bactericidal, anti-inflammatory, anti-allergic, anti-virus, anti-cancer, anti-rheumatic, insecticidal and herbicidal effects. At the same time, the γ-butyrolactone derivatives can be easily synthesized For many complex natural products, efficient synthesis of γ-butyrolactone structures has always been an important research direction in synthetic methodology and natural product synthesis chemistry. The synthesis of many optically active γ-butyr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D307/58A61P35/00
CPCC07D307/58A61P35/00
Inventor 胡文浩杨晓涵刘俊文张丹张梦楚
Owner SUN YAT SEN UNIV
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