γ-氨基丁酸衍生物的化学-酶法合成研究进展

Advances in the chemoenzymatic synthesis of gamma-aminobutyric acid derivatives

γ-氨基丁酸(gamma-aminobutyric acid,GABA)衍生物是一类治疗神经退行性疾病的高效抑制性神经递质药物,市场需求较大。目前,GABA衍生物的主要合成策略为化学法,面临工艺复杂、产率低、原子经济性低、环境负担大等诸多挑战。化学-酶法合成GABA衍生物具有原子经济性高、产率高、环境友好等优点,受到业内人士越来越多的关注。本文综述了GABA衍生物的化学和化学-酶合成方法,并在此基础上,介绍了典型GABA衍生物(如加巴喷丁、普瑞巴林和布瓦西坦等)的工业合成最新进展和未来发展方向。

Gamma-aminobutyric acid(GABA)derivatives are a class of effective inhibitory neurotransmitters for treating neurodegenerative diseases,with an immense market demand.Chemical methods are currently the main synthetic strategies for GABA derivatives,facing challenges such as complex processes,low yields,low atom economy,and environmental burden.In recent years,chemoenzymatic synthesis of GABA derivatives has garnered increasing attention because of the high atom economy,high yields,and environmental friendliness.This article reviews the latest advances in the chemical synthesis and chemoenzymatic synthesis of GABA derivatives.Furthermore,it introduces the progress in the industrial synthesis of representative GABA derivatives such as gabapentin,pregabalin,and brivaracetam and prospects the future development of GABA derivatives.