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Novel tetracyclonaphthooxazole derivative and preparation method thereof

A technology of naphthooxazole derivatives and derivatives, which is applied in the field of novel tetracyclic naphthooxazole derivatives and their preparation, and can solve the problems of limiting the application of such compounds, cumbersome synthesis methods, and low synthesis efficiency

Inactive Publication Date: 2015-07-08
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the existing synthesis methods of naphthooxazole derivatives are relatively cumbersome and the synthesis efficiency is not high, which limits the application of such compounds

Method used

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  • Novel tetracyclonaphthooxazole derivative and preparation method thereof
  • Novel tetracyclonaphthooxazole derivative and preparation method thereof
  • Novel tetracyclonaphthooxazole derivative and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049]

[0050] The preparation of 2-substituted aminoquinone substrates refers to Khodade, V.S.; Dharmaraja, A.T.; Chakrapani, H.Bioorg.Med.Chem.Lett.2012,22,3766.

[0051] Weigh 86mg (0.4mmol) 2-n-propylamino-1,4-naphthoquinone, 107mg (0.6mmol) diphenylacetylene, 12mg (0.02mmol) [Rh(Cp*)Cl 2 ] 2 (Cp*=pentamethylcyclopentadiene), 12mg (0.04mmol) AgSbF 6 and 160 mg (0.8 mmol) Cu(OAc) 2 .H 2 O was added to a round bottom reaction flask, dissolved with 2mL t-AmOH, and heated at 120°C for 6h to complete the reaction. Added 10 mL of water, extracted three times with ethyl acetate (5 mL x3), combined the organic phases, washed with saturated brine, dried over anhydrous sodium sulfate, evaporated the solvent under reduced pressure, and separated by silica gel column chromatography to obtain 113 mg of light yellow solid compound 1, Yield 73%; 25mg light yellow solid compound 29, yield 14%.

[0052] Compound 1:

[0053] 1 H NMR (300MHz, CDCl 3 )δ7.60(d,J=8.4Hz,1H),7.33(m,5H),...

Embodiment 2

[0057]

[0058] Except that diphenylacetylene was replaced by di-p-methylphenylacetylene, 110 mg of light yellow solid compound 2 was prepared according to the method of Example 1, and the yield was 66%. 27 mg of light yellow solid compound 30, yield 14%.

[0059] Compound 2:

[0060] 1 H NMR (400MHz, CDCl 3 )δ7.62(d,J=8.3Hz,1H),7.27(m,5H),7.17(m,3H),7.03(d,J=8.1Hz,2H),6.53(m,1H),3.06( q,J=7.6Hz,2H),2.42(s,3H),2.32(s,3H),1.53(t,J=7.6Hz,3H); 13 C NMR (101MHz, CDCl 3 )δ168.1, 150.0, 149.9, 140.5, 138.5, 138.4, 137.1, 133.5, 132.3, 131.2, 130.9, 129.8, 128.8, 128.6, 128.4, 120.5, 120.0, 115.8, 115.6, 98.3, 21.3 (2) EI-MS (m / z) 417 (M + ), HRMS C 29 h 23 NO 2 [M + ], calculated value: 417.1729, measured value: 417.1728.

[0061] Compound 30:

[0062] 1 H NMR (300MHz, CDCl 3 )δ7.63(dd,J=8.3,0.9Hz,1H),7.29(dd,J=8.2,7.5Hz,1H),7.16(m,7H),7.00(d,J=7.9Hz,2H), 6.54(dd, J=7.4,0.9Hz,1H),6.18(q,J=6.7Hz,1H),2.38(s,3H),2.28(s,3H),2.18(s,3H),1.80(d ,J=6.7Hz,3H); 13 C NMR (1...

Embodiment 3

[0064]

[0065] Except that diphenylacetylene was replaced by di-p-chlorophenylacetylene, 117 mg of light yellow solid compound 3 was prepared according to the method of Example 1, and the yield was 64%.

[0066] 1 H NMR (300MHz, CDCl 3 )δ7.61(d,J=8.4Hz,1H),7.36(d,J=8.3Hz,2H),7.24(m,2H),7.18(m,4H),7.14(m,2H),6.43( d,J=7.4Hz,1H),3.02(q,J=7.6Hz,2H),1.49(t,J=7.6Hz,3H); 13 C NMR (101MHz, CDCl 3 )δ168.3, 149.5, 149.1, 140.7, 138.6, 134.7, 133.8, 133.5, 132.4, 132.1, 130.2, 129.6, 128.6, 128.1, 120.3, 120.0, 116.6, 115.7, 115.5, 98.1-MS, 22.3 / z)457(M + ), HRMS C 27 h 17 NO 2 Cl 2 [M + ], calculated value: 457.0636, measured value: 457.0633.

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Abstract

The invention discloses a novel tetracyclonaphthooxazole derivative. The structure of the novel tetracyclonaphthooxazole derivative is represented by general formula (I) shown in the specification. The invention also discloses a preparation method of the tetracyclonaphthooxazole derivative. The method allows the tetracyclonaphthooxazole derivative to be innovatively synthesized through using a carbon hydrogen activation serial reaction with amino substituted quinone as a reaction substrate. The method has the advantages of simplicity, easy implementation and high efficiency. The synthetic tetracyclonaphthooxazole derivative has a similar structure with a traditional DNA clastogen, can inhibit cell proliferation and growth, and has antibacterial, antifungal, anti-HIV and antitumor bioactivity. The invention also discloses an application of above compounds as a cell proliferation and growth inhibitor, and an application of the compounds in the preparation of antitumor medicines.

Description

technical field [0001] The invention relates to the fields of organic chemistry and medicinal chemistry, in particular to a novel tetracyclic naphthooxazole derivative and a preparation method thereof. Background technique [0002] As dominant skeletons, benzoxazole and naphthooxazole widely exist in a variety of active natural products and synthetic molecular structures. It has various biological activities such as anti-bacteria, anti-fungal, anti-HIV, and anti-tumor. [0003] In recent years, scientists have successively discovered some other biologically active compounds containing benzoxazole and naphthooxazole skeleton molecules. In 1999, González et al. reported that the compound pseudopteroxazol could inhibit the growth of tuberculosis bacteria (Rodríguez, A.D.; Ramire, C.; Rodríguez, I.I.; González, E.Org. Lett. 1999, 1, 527); in 2013, Shin et al. reported that the compound Herqueioxazole aureus sortase A enzyme has significant inhibitory activity (Julianti, E.; Le...

Claims

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Application Information

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IPC IPC(8): C07D498/06A61P35/00A61P31/04A61P31/10A61P31/18
CPCC07D498/06
Inventor 张翱缪泽鸿王美凝宋姗姗
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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