苯并-α-吡喃酮类生物活性物质的合成

Synthesis of some biologically active coumarins

从简单的原料2,3,4-三甲氧基苯甲醛出发,经选择性地去甲基化、Knoevenagel缩合关环、硝基还原及酰化等反应,设计合成了3个未见文献报道的3位酰氨基取代的苯并-α-吡喃酮类生物活性物质。其结构经1H NMR、13C NMR、IR分析确证。同时对合成过程中最关键的Knoevenagel缩合反应条件进行了研究,降低了反应溶剂的毒性并通过正交实验优化了合成工艺,确定较佳工艺条件为:以甲苯与环己烷(V甲苯∶V环己烷=7∶3)为溶剂,哌啶为催化剂,n(2-羟基-3,4-二甲氧基苯甲醛)∶n(硝基乙酸甲酯)∶n(催化剂)=1∶1.2∶0.20,反应温度98℃±2℃,反应时间6 h,平均收率87.2%,高于文献值。目标化合物是一种新的苯并-α-吡喃酮类物质,具有潜在的抗癌活性,有望成为新的抗癌药物。

Three novel derivatives of 2H-1-benzopyran-2-one were designed and synthesized from 2,3,4-trimethoxybenzaldehyde by methoxy reduction,Knoevenagel,nitro reduction and acylation reaction. Its structure was confirmed by 1H-NMR,13C-NMR,IR analysis. Experiments based upon orthogonal design with four factors and three levels were carried out for the optimization of Knoevenagel reaction condition. The experimental results show that the optimal condition is found as follows:using toluene and cyclohexane[V(toluene)∶V(cyclohexane)=7∶3] as solvent and piperidine as catalyst,n(2-hydroxy-3,4 dimethoxybenzaldehyde)∶n(methyl nitroacetate)∶n(catalyst)=1∶1.2∶0.20,the reaction temperature of 98℃±2℃and reaction time of 6h. Under this optimal condition,the average yield can reach 87.2%,higher than the values in literature. Target compounds are novel coumarin derivatives,with potential anticancer activity.