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.