Synthesis And Antimicrobial Activity Of4-hydroxy-2-pyridone Analogs

It is import to study the structure-activity relationships of4-hydroxy-2-pyridone since itwidely exists in many natural active alkaloids. The advance in4-hydroxy-2-pyridone is reviewedin this article, including structure features, bioactivity, and synthetic methodology. Based on this,we concentrated on the research of modification and the activity in anti-fungus and anti-bacteria ofIlicicolin H as a lead compound. The main work is as follows:(1).The acyl azide compound was obtained from p-methoxycinnamic acid in the presence ofdiphenylphosphorylazide (DPPA) and then was used to synthesis the corresponding isocyanate viaCurtius rearrangement. The isocyanate was used to react with two different β-carbonyl esters inthe presence of NaH, which gave the products (E)-ethyl-3-((4-methoxystyryl)amino)-3-oxopropanoate and (E)-ethyl-2-(cyclohexanecarbonyl)-3-((4-methoxystyryl)amino)-3-oxo-propanoate, respectively. We analyzed the mechanism of the way to form the former compoundand got the aimed cyclized product from the latter.(2).The acyl azide compound was synthesized from the p-hydroxycinnamic acid, which wasacetylated by acetic anhydride, in the presence of diphenylphosphorylazide (DPPA) and then wasused to synthesis the corresponding isocyanate via Curtius rearrangement. The isocyanate wasused to react with three different β-carbonyl esters in the presence of NaH, which gave three(E)-ethyl-3-((4-acetoxystyryl) amino)-3-oxopropanoate derivatives. And then these compoundswere cyclized to obtain4-hydroxy-5-(4-acetoxyphenyl)-2-pyridone-3-carboxamide aimedproducts in2-methoxyethyl ether. Finally, we used K2CO3as the deacetylated reagent and gotanother three aimed products.(3).The condition of the de-protection of hydroxyl group was optimized in the synthesis of 4-hydroxy-5-(4-hydroxyphenyl)-2--pyridone-3-carboxamide.(4).The antifungal and antibacterial activity of the bimolecular cyclized products werescreened by filter paper diffusion and broth dilution. The analysis results indicate that thesecompounds have significant antifungal activity against Candida albicans, weak activity againstYeast, but no inhibitory activity on E.coli and Staphylococcus aureus. Both of the two compounds’MIC against Candida albicans are below50μg/mL.(5).Totally, nineteen compounds were synthesized. And sixteen of them had not been reportedin the literature yet, including eight4-hydroxy-2-pyridone targeting compounds. All of thecompounds were characterized by IR,1H NMR,13C NMR, MS or HRMS analysis to conformtheir structures.