Synthesis Of4-Hydroxy-2-Pyridone Analogs

4-Hydroxy-2-pyridones exhibited excellent biological activities such as antifungal, antibacterial, and cytotoxic activity and so on. The recent progresses in structural modification, synthesis and biological activity of4-hydroxy-2-pyridones were reviewed. After discussed the advantages and disadvantages of various synthetic methods, the target compounds were designed and synthesized through Ilicicolin H as lead compound. The thesis includes the followings:(1) Pyridine-N-oxide was prepared from the reaction between pyridine and H2O2.4-Methoxy pyridine-N-oxide was prepared through nitration and replaced the nitro group by sodium methoxide.4-Methoxy-2-pyridone was obtained from oxidation and hydrolysis by former product.(2) Cinnamoyl azide was synthesized from the reaction between cinnamic acid and diphenyl phosphorazidate(DPPA),4-methoxy cinnamoyl azide was obtained in the same way. Then styryl isocyanates were generated by heating the azides followed by Curtuis Rearrangement. The intermediates,(E)-diethyl2-(styrylcarbamoyl)malonate,(E)-ethyl2-((E)-styrylcarbamoyl)-3-hydr-oxybut-2-enoate and (E)-ethyl2-{[(E)-4-methoxystyryl]carbamoyl}-3-hydroxybut-2-enoate were prepared from the vinyl isocyanate and diethyl malonate or ethyl acetoacetate.4-hydroxy-2-pyridones were synthesized after cyclization.(3) Cyclization experimental results of (E)-diethyl2-(styrylcarbamnoyl)malonate showed that (E)-4-hydroxy-2-oxo-5-phenyl-N-styryl-1,2-dihydropyridine-3-carboxamide was obtained in diphenyl ether at210℃-250℃in43.8%yield. However, Ethyl4-hydroxy-2-oxo-5-phenyl-1,2- dihydropyridine-3-carboxylate was synthesized in xylene in44.9%yield.(4) Single crystal of (E)-ethyl2-{[(E)-4-methoxystyryl]carbamoyl}-3-hydroxybut-2-enoate was obtained by dissolving the compound in petroleum ether and ethyl acetate (1:1), It was monoclinic. Three-dimensional structure of the crystal structure was formed by intramolecular hydrogen bonding interaction.(5) Totally, seventeen compounds were synthesized. Four target compounds and three intermediates have not been reported. The structures of these compounds were characterized by IR,’H NMR,13C NMR, MS and HRMS.