引入含氟砌块对天然产物母核5-色酮骨架的构效解析

Structure-activity analysis of natural products core 5-chromone skeleton by introducing fluorine-containing building blocks

目的将极强电负性的氟原子引入2-羟基-2-三氟甲基-3-噻吩-5-色酮C_(23)H_(21)BrF_(3)NO_(3)S的芳香性结构,获得高脂溶性、高稳定的化合物。方法以对溴基苯甲醛、达咪酮、4,4,4-三氟-1-(噻吩-2-基)丁烷-1,3-二酮和醋酸铵为原料,少量的乙醇作溶剂,多组分一锅法合成目标化合物。核磁共振谱(^(1)H-NMR和^(13)C-NMR)、红外光谱(IR)、高分辨质谱(HRMS)和X射线单晶衍射确证目标化合物的结构,并分析该结构的各平面角度。结果获得目标产物,即2-羟基-7,7-二甲基-3-(噻吩-2-羰基)-4-(对溴苯基)-2-(三氟甲基)-3,4,7,8-四氢-5(6H)-色酮。产物结构经核磁、红外和高分辨质谱确证。单晶X射线衍射分析显示,该产物的晶体结构属正交晶系,空间群Pbca。采用直接法解析该晶体结构,全矩阵最小二乘法修正的原子参数显示,最终的偏离因子为R=0.0464,wR=0.1133。该分子结构中新构筑的吡啶环为半椅式构象。结论本研究通过多组分反应将三氟甲基高效且便捷地引入到色酮骨架。

Objective To introduce an extremely electronegative fluorine atom into the aromatic structure of 2-hydroxy-2-trifluoromethyl-3-thiophene-5-chromone C_(23)H_(21)BrF_(3)NO_(3)S,so as to obtain a target compound with enhanced lipid solubility and stability.Methods In the current study,p-bromobenzaldehyde,dammidone,4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione and ammonium acetate were used as raw materials,while a small amount of ethanol was used as the solvent.The target compound was synthesized by the multi-component one-pot method.The crystal structure was verified by^(1)H-NMR and^(13)C-NMR,IR,HRMS,and X-ray diffraction method and the angle of each surface was analyzed.Results The target product was obtained,that is 2-hydroxy-7,7-dimethy-3-(thiophene-2-carbony)-4-(p-bromophenyl)-2-(trifluoromethyl)-3,4,7,8-tetrahydro-5(6H)-chromone.The crystal structure was verified by^(1)H-NMR and^(13)C-NMR,IR,and HRMS.According to X-ray diffraction,the crystal structure belonged to the orthorhombic system,and the space group was Pbca.In addition,the direct method was used to analyze the crystal structure,and the atomic parameters corrected by the full matrix least square method showed that the final deviation factor was R=0.0464,and wR=0.1133.The newly constructed pyridine ring in the molecular structure has a half-chair conformation.Conclusions The trifluoromethyl group was efficiently and conveniently introduced into the chromone framework through a multi-component reaction.