摘要
本文详细报道了具有抗乙酰胆碱酯酶(AChE)活性的新型石松类生物碱:消旋石杉碱甲[(±)-Huperzine A]的全合成。采用5-乙氧羰基-6-甲基吡啶酮-2(7)为原料,经7步反应合成重要中间体(14),后者经Michael加成,获三环系化合物(17),再经Wittig反应后,分得相应几何构型的化合物(24),最后经改良的Curtius重排和脱除保护基等反应,获全合成终产物(1),并与天然石杉碱甲的IR,~1HNMR,MS相一致。
Details of the total synthesis of (±)-huperzine A, which exhibits potent activity as an inhibitor of reversible aeetylcholinesterase are described in this paper.After 7 reaction steps from 5-ethoxycarbonyl-6-methyl-2-pyridone(7) as the starting material, the key intermediate 2-methoxy-5-methoxyearbonyl-6-keto-5, 6, 7, 8-tetrahydroquinoline (14) was obtained in 40％ overall yield. Michael addition of the compound (14) with methacrolein rendered tricyclic compound (17), which was further made to undergo a series of reactions, including the Wittig reaction, modified Curtius rearrangement as well as the reaction of deprotective group to give the synthesized (±)-Huperzine A, identical to the natural specimen in IR, ~1HNMR and MS.
出处
《中国药物化学杂志》
CAS
CSCD
1992年第2期1-8,共8页
Chinese Journal of Medicinal Chemistry
