石松生物碱研究进展

本文综述了自1994年以来天然石松生物碱的研究进展和石衫碱甲的抗乙酰胆酯酶生物活性及它的构效关系研究。按照石松生物碱的分类方法，系统归纳了lycopodine,lycodine,fawcettimine和misceualleous四种类型生物碱的结构特点和内在的相互关系，以及各种类型的新天然化合物。石杉碱甲是由我国科学家首先发现的一个天然的石松生物碱，药理实验证明它是一个高选择性的乙酰胆碱酯酶抑制剂，具有口服生物利用度高、作用时间长、副反应小的特点，优于巳上市的第一代治疗老年痴呆药物E2020，Tacrine，Physostigmine和Galanthamine。已合成的大量的石杉碱甲类似物的药理实验表明，作为AChE抑制剂，石杉碱甲是一个紧凑的结构，现有的结构要素一个都不能少。不过。以天然石杉碱甲为原料合成的席夫碱衍生物和用石杉碱甲的结构片断与Tacrine相结合的类似物研究取得了可喜的进展。

Progress in the Research of Lycopodium Alkaloids

The Lycopodiwn alkaloids discovered from January, 1994 to March, 2003, and the research progress of huperzine A (HA) were reviewed. This paper illustrated the structure characters of lycopodine-type, lycodine-type, fawcettimine-type and miscellaneous group, common four types of Lycopodium alkaloids. Pharmacological studies showed HA was a potent, high selective, and reversible acetycholinesterase(AChE) inhibitor. The structure-activity relationship studies on HA disclosed that HA possesses a concise structure, in which most of structure fragments, such as two double bonds, pyridone ring, tri-carbon bridge ring, and the N-atom of the amino group were necessary for its high anti- AchE activity. Recently, some HA Schiff base derivatives and HA-tacrine hybrids were reported that they had near or better anti-AChE activity than HA.