In vivo transformations of dihydroartemisinic acid in Artemisia annua plants
In vivo transformations of dihydroartemisinic acid in Artemisia annua plants
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DOI：
10.1016/j.tet.2003.11.070
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发表时间：
2004-01-26
期刊：
影响因子：
2.1
通讯作者：
Sy, LK
中科院分区：
文献类型：
--
作者：
Brown, GD;Sy, LK
[15-（CH_3）-C-13-H-2]-双氢青蒿酸（2a）和[15-（CH_3）-H-2]-双氢青蒿酸（2b）通过根被供给到完整的黄花蒿植物中，并通过一维H-2 NMR光谱和二维C-13-H-2相关NMR光谱（C-13-（2）H COSY）研究它们在体内的转化。标记的双氢青蒿酸在A. annua，虽然根中的转化要慢得多，也更有限。这16种代谢产物中有15种以前已报道为A. annua。有证据表明，在体内转化的双氢青蒿酸的第一步是形成烯丙基氢过氧化物的分子氧与δ（4，5）-双键在这个化合物的反应。所有16种次级代谢物的来源可能会被解释为这些氢过氧化物的已知的进一步反应。在体内的双氢青蒿酸的转化的定性模式基本上是不变的，当比较植物，这一直保持活着，植物被允许死亡后喂养的标记前体。这一点，再加上观察到的模式的转化2在体内表现出非常密切的平行自发自氧化化学2，这是我们最近在体外证明，使我们得出结论，主要的"代谢途径"的双氢青蒿酸在A。annua涉及其自发自氧化和随后的衍生自2的烯丙基氢过氧化物的自发反应。可能不需要在任何随后的生物发生步骤中引起酶的参与，从而产生在A.黄花树作为天然产品。(C)2003 Elsevier Ltd.保留所有权利。
[15-(CH3)-C-13-H-2]-dihydroartemisinic acid (2a) and [15-(CH3)-H-2]-dihydroartemisinic acid (2b) have been fed via the root to intact Artemisia annua plants and their transformations studied in vivo by one-dimensional H-2 NMR spectroscopy and two-dimensional, C-13-H-2 correlation NMR spectroscopy (C-13-(2) H COSY). Labelled dihydroartemisinic acid was transformed into 16 12-carboxy-amorphane and cadinane sesquiterpenes within a few days in the aerial parts of A. annua, although transformations in the root were much slower and more limited. Fifteen of these 16 metabolites have been reported previously as natural products from A. annua. Evidence is presented that the first step in the transformation of dihydroartemisinic acid in vivo is the formation of allylic hydroperoxides by the reaction of molecular oxygen with the Delta(4,5)-double bond in this compound. The origin of all 16 secondary metabolites might then be explained by the known further reactions of such hydroperoxides. The qualitative pattern for the transformations of dihydroartemisinic acid in vivo was essentially unaltered when a comparison was made between plants, which had been kept alive and plants which were allowed to die after feeding of the labelled precursor. This, coupled with the observation that the pattern of transformations of 2 in vivo demonstrated very close parallels with the spontaneous autoxidation chemistry for 2, which we have recently demonstrated in vitro, has lead us to conclude that the main 'metabolic route' for dihydroartemisinic acid in A. annua involves its spontaneous autoxidation and the subsequent spontaneous reactions of allylic hydroperoxides which are derived from 2. There may be no need to invoke the participation of enzymes in any of the later biogenetic steps leading to all 16 of the labelled 11,13-dihydro-amorphane sesquiterpenes which are found in A. annua as natural products. (C) 2003 Elsevier Ltd. All rights reserved.