In vivo transformations of artemisinic acid in Artemisia annua plants
In vivo transformations of artemisinic acid in Artemisia annua plants
复制标题
DOI：
10.1016/j.tet.2007.06.062
复制
发表时间：
2007-09-17
期刊：
影响因子：
2.1
通讯作者：
Sy, Lai-King
中科院分区：
文献类型：
--
作者：
Brown, Geoffrey D.;Sy, Lai-King
在15-位上用C-13和H-2标记的青蒿酸通过切下的茎被喂给完整的青蒿植物，并且通过1D和2D-NMR光谱研究其在体内的转化。已分离出七种标记代谢物，所有这些都是已知的该物种的天然产物。青蒿酸的转化--在一组植物中观察到，这组植物通过水耕法给药而保持存活，在一组植物中观察到，这组植物通过干燥而死亡--与最近描述的其11，13-二氢类似物二氢青蒿酸的转化密切相关。因此，似乎类似的机制，包括青蒿酸和二氢青蒿酸中δ（4，5）双键的自发自氧化和随后所得烯丙基氢过氧化物的重排，可能涉及两种化合物所经历的生物转化。所有的倍半萜代谢物，这是从青蒿酸的体内转化获得的保留其在11，13-位的不饱和度，没有证据表明转化为任何11，13-二氢代谢物，包括青蒿素，抗疟疾药物，这是由A. annua。这一观察结果导致了一个统一的生物合成方案的建议，该方案解释了许多作为天然产物从A. annua。在该方案中，在从紫穗槐-4，11-二烯开始的生物合成途径中存在分叉，导致青蒿酸或二氢青蒿酸;然后这两个确定的前体分别是两个大家族的高度氧化的11，13-双烯和11，13-二氢倍半萜代谢物的亲本，这是从该物种中已知的。(C)2007爱思唯尔有限公司版权所有。
Artemisinic acid labeled with both C-13 and H-2 at the 15-position has been fed to intact plants of Artemisia annua via the cut stem, and its in vivo transformations studied by 1D- and 2D-NMR spectroscopy. Seven labeled metabolites have been isolated, all of which are known as natural products from this species. The transformations of artemisinic acid-as observed both for a group of plants, which was kept alive by hydroponic administration of water and for a group, which was allowed to die by desiccation-closely paralleled those, which have been recently described for its 11,13-dihydro analog, dihydroartemisinic acid. It seems likely therefore that similar mechanisms, involving spontaneous autoxidation of the Delta(4,5) double bond in both artemisinic acid and dihydroartemisinic acid and subsequent rearrangements of the resultant allylic hydroperoxides, may be involved in the biological transformations, which are undergone by both compounds. All of the sesquiterpene metabolites, which were obtained from in vivo transformations of artemisinic acid retained their unsaturation at the 11,13-position, and there was no evidence for conversion into any 11,13-dihydro metabolite, including artemisinin, the antimalarial drug, which is produced by A. annua. This observation led to the proposal of a unified biosynthetic scheme, which accounts for the biogenesis of many of the amorphane and cadinane sesquiterpenes that have been isolated as natural products from A. annua. In this scheme, there is a bifurcation in the biosynthetic pathway starting from amorpha-4,11-diene leading to either artemisinic acid or dihydroartemisinic acid; these two committed precursors are then, respectively, the parents for the two large families of highly oxygenated 11,13-dehydro and 11,13-dihydro sesquiterpene metabolites, which are known from this species. (C) 2007 Elsevier Ltd. All rights reserved.