拉科酰胺的合成研究进展

拉科酰胺是一种新型N-甲基-D-门冬氨酸受体甘氨酸结合位点拮抗剂，它主要用于治疗癫痫和神经性疼痛。本文详细介绍了半合成法及全合成法制备拉科酰胺的研究进展。半合成法主要通过生物酶法或者手性拆分制备其前体原料R-丝氨酸及其衍生物，再经化学合成得到最终产物拉科酰胺。全合成法则以苯甲醇为原料，经缩合、催化水解、取代、保护氧化、脱保护缩合等反应得到拉科酰胺。分析了各种合成方法的优势及其存在的问题：半合成法的优势在于合成路线较短，反应易于进行，但也存在反应试剂昂贵、副反应多、收率低等缺点，而全合成法的优势在于原料易得、成本较低，其不足是反应步骤较长、拆分产率较低，因此拉科酰胺今后发展的方向应该是寻找更适合的合成路线以及现有的合成工艺的优化，同时提高原料来源以及降低反应试剂成本，使工业化成本大大降低。

Progress in the synthesis of Lacosamide

Lacosamide(LCM)，a novel antagonist of the glycinebinding site on N-methyl-D-aspartate（NMDA） receptors，is mainly applied to the treatment of epilepsy and neuropathic pain. This review is to introduce recent studies on the synthesis of Lacosamide through both total synthesis and semi-synthesis methods. For the semi-synthesis method，chemical resolution or enzymatic kinetic resolution is usually adopted for producing its precursor material R-serine and its derivatives，and then the final product Lacosamide is obtained by chemical synthesis. For the total synthesis method，benzyl alcohol is used as raw material，and the final product Lacosamide is then obtained through a series of reaction：condensation，catalyzed hydrolysis，substitution，protective oxidation，de-protective condensation. Furthermore，the advantages and disadvantages of both synthesis methods are analyzed：the advantages of semi-synthesis are that reactions are easy to be reached，and the synthesis procedure is short，but its disadvantages includes expensive reaction reagent，too many side-effects，low yield and so on；while total synthesis is featured as easy raw material obtaining and low cost，long reaction procedure and low resolution yield. Therefore，the future development of Lacosamide should follow a more suitable synthesis route and adopt the revised modern synthesis techniques. Besides，to reduce the industrial cost significantly，the resource of raw material should be improved and the cost of reaction reagent should be reduced also.