The biosynthesis of papaverine proceeds via (S)-reticuline
The biosynthesis of papaverine proceeds via (S)-reticuline
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DOI：
10.1016/j.phytochem.2010.04.022
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发表时间：
2010-08-01
期刊：
影响因子：
3.8
通讯作者：
Zenk, Meinhart H.
中科院分区：
文献类型：
--
作者：
Han, Xu;Lamshoeft, Marc;Zenk, Meinhart H.
罂粟碱是最早的鸦片生物碱之一，其生物合成假说是在理论基础上发展起来的。Norlaudanosoline （=tetrahydropapaveroline）被认为是多种含氮植物代谢物的直接前体生物碱。这个四羟基化的化合物被认为是完全o -甲基化的。得到的四氢罂粟碱会芳香化成罂粟碱。根据实验数据，这条路径需要修改。将前体施用于8天大的木瓜幼苗，然后直接检查植物提取物中稳定同位素标记的前体的代谢命运，而不进一步纯化代谢物，从而阐明了罂粟碱在体内的途径。中心和最早的苯基异喹啉生物碱不是四氧合的去甲劳达索碱，而是三羟基化的去甲劳索碱，它进一步转化为(S)-网状碱，这是罂粟生物碱的已知前体。罂粟碱途径通过(S)-网状氨酸甲基化生成(S)-劳丁氨酸而打开。第二次甲基化，在3'的位置上，得到了鸦片碱，这两种生物碱都是从罂粟中提取的。随后，劳达苷的n -去甲基化产生已知的罂粟碱前体：四氢罂粟碱。对随后芳构化反应的检查确定了中间产物1,2-二氢罂粟碱的存在，并对其进行了表征。罂粟碱的最后一步是1,2键的脱氢，得到目标化合物罂粟碱。我们在此得出结论，先前声称的去甲网碱在罂粟碱的生物合成中不起作用。(C) 2010 Elsevier Ltd.版权所有。
Papaverine is one of the earliest opium alkaloids for which a biosynthetic hypothesis was developed on theoretical grounds. Norlaudanosoline (=tetrahydropapaveroline) was claimed as the immediate precursor alkaloid for a multitude of nitrogen containing plant metabolites. This tetrahydroxylated compound was proposed to be fully O-methylated. The resulting tetrahydropapaverine should then aromatize to papaverine. In view of experimental data, this pathway has to be revised. Precursor administration to 8-day-old seedlings of Papaver followed by direct examination of the metabolic fate of the stable-isotope-labeled precursors in the total plant extract, without further purification of the metabolites, led to elucidation of the papaverine pathway in vivo. The central and earliest benzylisoquinoline alkaloid is not the tetraoxygenated norlaudanosoline, but instead the trihydroxylated norcoclaurine that is further converted into (S)-reticuline, the established precursor for poppy alkaloids. The papaverine pathway is opened by the methylation of (S)-reticuline to generate (S)-laudanine. A second methylation at the 3' position of laudanine leads to laudanosine, both known alkaloids from the opium poppy. Subsequent N-demethylation of laudanosine yields the known precursor of papaverine: tetrahydropapaverine. Inspection of the subsequent aromatization reaction established the presence of an intermediate, 1,2-dihydropapaverine, which has been characterized. The final step to papaverine is dehydrogenation of the 1,2-bond, yielding the target compound papaverine. We conclusively show herein that the previously claimed norreticuline does not play a role in the biosynthesis of papaverine. (C) 2010 Elsevier Ltd. All rights reserved.