Studies on Synthesis of a Novel, Broad-Spectrum Antitumor Compound 2-(1-hydroxy-4-oxo-cyclohexa-2, 5-dienyl)-pyran-4-one

Author(s): Xiaohua Wang , Liu Yang , Pingping Xue , Jinlan Ruan .

Journal Name: Letters in Organic Chemistry

Volume 14 , Issue 1 , 2017

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Background: Based on the previous studies, used protoapigenone as a model, we adopted chemical synthesis methods to develop the new compounds. It was specifically named as 2-(1-hydroxy- 4-oxo-2, 5-cyclohexadien-1-yl)-4H-Pyran-4-one, including a core group: 1-hydroxycyclohexa-2, 5- dien-4-one. Through our research it significantly inhibited human gynecological tumor, prostate tumor, digestive system tumors and hematological tumors, but without affecting the normal hematopoietic system and immune system. Additionally, this compound can effectively inhibit tumor growth in H22 mice with tumor, while had no effect to peripheral blood leukocytes, ratio of peripheral blood granulocyte cell and lymphocyte, thymus index and spleen index. But the synthetic methods of the compound has been plaguing us and now we invent a new synthetic process of it. The present invention in this article provides the method capable of industrially producing the target product.

Methods: In this article we report on a new route to the synthesis of 2- (1-hydroxy-4-oxo-cyclohexa-2, 5-dienyl)-pyran-4-one (1). Compound 1 was prepared from 4-Methoxyacetophenone by the trimethylsilylation, trimethylsilyl enol ethers intermediate 3 was generated. Using the intermediate 3 with Oxalyl chloride, β-diketone 4 have been prepared. Under a thermal condition, Compound 4 reacted with ethyl vinyl ether to give pyran-4-ones 5. Demethylation of Compound 4 by BBr3, then through oxidization to give the target compound.

Results: The target compound can be efficiently prepared by the method reported in this article. And the overall yield rises to about 25.1% much higher than the existing methods. All of the intermediates were structurally characterized, physico-chemical properties of the synthetic compounds are as follows: 1H NMR (400 MHz, DMSO) δ 8.08 (d, J = 5.8 Hz, 1H, CH), 7.07 (s, 1H, CH), 6.93 (d, J = 10.0 Hz, 2H, ArH), 6.52 (d, J = 2.5 Hz, 1H, CH), 6.32 – 6.23 (m, 3H, ArH, OH); 13C NMR (100 MHz, DMSO) δ 185.3, 178.3, 167.1, 156.9, 148.4, 129.1, 116.9, 113.5, 69.0; HRMS: calcd for C11H8O4 [M-H]- 203.0344, found 203.0347.

Conclusion: The synthesis can be performed in “one pot”, and the target product is yielded. Therefore, the product can be readily separated and purified, whereby the process can be carried out in simple manner at high efficiency. And the overall yield much higher than the existing methods. Thus, the production process of the present invention can reduce production cost, and also, shorten production time.

Keywords: α, β-unsaturated ketones, 4H-pyran-4-ones, tumor growth inhibition.

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Article Details

Year: 2017
Page: [39 - 42]
Pages: 4
DOI: 10.2174/1570178614666161205161634
Price: $58

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