2,3 - Dihydro - 3 - (hydroxymethyl)-1 ,4 - Benzoxazine Derivatives Design, Synthesis And Biological Activity Study

The 2,3-dihydro-1,4-benzodioxine system has been widely used as a substructure of several biologically interesting agents and hence, a variety of reports have been presented for their synthesis and biological evaluation of compounds including this ring.The chemical synthesis results showed that the reaction in the condition of 1 equiv. of 2-nitroaroxymethyloxiranes with 3 equiv. of iron powder and 9 equiv. glacial acetic acid in the mixture solvents of alcohol and water (v/v = 9:1) at refluxing temperature which was the optimized condition gave the highest yield. When 2-nitroaroxymethyloxiranes with electron-withdrawing groups in benzene ring such as 4-chloro, 4,6-dichloro and 6-chloro were subjected to the optimized condition, the reaction yields were relatively higher. The competitive formation of the polar byproducts was nearly not observed. However, when there was an electron-donating group in benzene ring such as 4-methyl, 4-tert-butyl, the reaction yields were relatively lower. Though 2,3-Dihydro-3-hydroxymethyl-6-amino-1,4-benzoxazine was difficult to be purified, the yield still can reached 42 percent. The structure of 2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine was characterized by ¹³C NMR, ¹H NMR, IR, MS and elemental analysis spectral data. The structures of other compounds were characterized by ¹H NMR, IR, MS and elemental analysis spectral data.The biological evaluation results showed that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine was the most effective small molecule in promoting HUVEC apoptosis and inhibiting A549 cell proliferation, but 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine could remarkably inhibit HUVEC apoptosis and might induce the formation of microvessel. These findings lead us to find their targets and to investigate the mechanisms of the small molecules acting in controlling cell proliferation, differentiation and apoptosis in our next researches.In this paper, we also investigated the synthesis of 3-formylchromones. 3-formylchromones had been one of the most important and useful intermediates. Modification of 3-formylchromones can give a series of heterocycle compounds. By far the most convenient method of synthesizing 3-formylchromone is by the Vilsmeier-Haack reaction. According to this method, we synthesized two 3-formylchromones and...