Synthesis Of4-Hydroxy-2-Pyridone Analogs

The thesis mainly includes the following two parts:Advances in4-hydroxy-2-pyridones as natural alkaloids, and the structural modification of Ilicicolin H.Advances in4-hydroxy-2-pyridones as natural alkaloids:Recent progress on4-hydroxy-2-pyridones is reviewed in detail, especially at the structure features, bioactivities and synthetic methodology.The structural modification of Ilicicolin H:We adopt the method of simplicity and introduce new groups to synthesize a series of analogues. The antifungal activity and structure-activity relationship was discussed. The present work comprises the following research:1. Acyl azides was synthesized by the reaction of acrylic acid derivatives with Diphenylphosphoryl azide (DPPA). Isocyanate were generated from acyl azides by Curtius rearrangement. The five cyclization intermediates2-carbamoyl-3-hydroxy-2-butenoates were prepared from the isocyanate and ethyl acetoacetate.3-acetyl-4-hydroxy-2-pyridones were obtained by heating the intermediates in diphenyl ether at220-230℃.2. Four2-carbamoyl malonate cyclization intermediates were obtained by the reaction of isocyanate and diethyl malonate.4-hydroxy-2-pyridone-3-carboxylates were synthesized by refluxing the2-carbamoyl malonates in xylene. However, if the intermediates were treated in diphenyl ether at220-230℃, the4-hydroxy-2-pyridone-3-carboxamides were obtained. The structure s were confirmed by spectroscopic analysis.3. We explored the reaction of Ethyl4-hydroxy-5-(4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate with excess CH3I. The experimental results show that the methyl can only be connected to the N atom, not the hydroxyl group.4. A single crystal for compound3-acetyl-4-hydroxy-5-(4-methoxyphenyl)-1-methylpyridin-2(1H)-one was cultured in DCM:methanol=1:1. The single crystal structure suggests that the hydrogen bonds formed between4-hydroxy and3-acetyl. 5. Totally, thirty seven compounds were designed and synthesized, thirty three of them had not yet been reported. Fourteen target4-hydroxy-2-pyridones were synthesized. Their structures were characterized by IR,1H NMR,13C NMR and HRMS analysis.