Biosynthesis of the Amaryllidaceae alkaloid galanthamine
Biosynthesis of the Amaryllidaceae alkaloid galanthamine
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DOI：
10.1016/s0031-9422(97)01024-8
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发表时间：
1998-10-01
期刊：
影响因子：
3.8
通讯作者：
Zenk, MH
中科院分区：
文献类型：
--
作者：
Eichhorn, J;Takada, T;Zenk, MH
应用放射性以及C-13-标记的4 '-O-甲基去甲颠茄碱到田间生长的Leucojum aestivum植物的器官中，分别导致最佳掺入加兰他敏（27%）和N-去甲基加兰他敏（31%）。与基于文献结果的预期相反，N-甲基化4 '-O-甲基降颠茄碱在L.并且掺入加兰他敏以及N-去甲基加兰他敏中的速率仅为4 '-O-甲基降贝拉定的约1/3。此外，它表明，N-去甲基加兰他敏是N-甲基化加兰他敏在生物合成的最后一步。本文提出了加兰他敏生物合成的一个改进方案，包括4 '-O-甲基降贝拉定与假定的二烯酮发生酚氧化偶联，二烯酮经历醚桥的自发闭合产生N-去甲基那维定，N-去甲基那维定经立体选择性还原和N-甲基化产生胆碱酯酶抑制剂加兰他敏。(C)1998爱思唯尔科技有限公司版权所有。
Application of radioactively as well as C-13-labelled 4'-O-methylnorbelladine to organs of field grown Leucojum aestivum plants resulted in an optimal incorporation into galanthamine (27%), and N-demethylgalanthamine (31%), respectively. In contrast to expectations based on results from the literature, the N-methylated 4'-O-methylnorbelladine was metabolized into a minor extent in L. aestivum and was incorporated into galanthamine as well as into N-demethylgalanthamine to only about 1/3 of the rate of 4'-O-methylnorbelladine. Furthermore, it was shown that N-demethylgalanthamine is N-methylated to galanthamine in the final step of biosynthesis. A revised scheme for the biosynthesis of galanthamine is presented involving the phenol oxidative coupling of 4'-O-methylnorbelladine to a postulated dienone which undergoes spontaneous closure of the ether bridge to yield N-demethylnarwedine which upon stereoselective reduction and N-methylation yields the cholineesterase inhibitor galanthamine. (C) 1998 Elsevier Science Ltd. All right reserved.