氘代阿戈美拉汀的合成

Synthesis of deuterium-labeled agomelatine

以苯酚为原料,氘代碘甲烷与氘代醋酸酐为氘代试剂.经过氘代甲基化、傅克酰基化、克脑文盖尔缩合、芳构化、还原及氘代乙酰化反应得到氘代标记的阿戈美拉汀(1).该合成路线简洁,原料易得、反应条件易于控制,总收率为15.2%,化学纯度为99.97%,氘代丰度大于98%.目标化合物结构经质谱、核磁共振等表征确定可用于其药代动力学研究.

Agomelatine‐d6 （1） was synthesized from phenol via deuterated methylation ,Friedel‐crafts acylation ,Knoevenagel condensation ,aromatization ,reduction and deuterated acetyla‐tion .Deuterium methyl iodide and acetic anhydride were used as labeling reagents .The syn‐thetic method was simple and efficient ,and all starting materials used in this study were com‐mercially available .The total yield was 15 .2% ,and the structure of the target compound was confirmed by MS and NMR .Its chemical purity was 99 .97% and isotopic enrichment exceeded 98% .It can be used as an internal standard for pharmacological studies .