amorph-4-ene-12-ol | 855425-50-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: amorph-4-ene-12-ol
• 英文别名: Dihydroartemisinic alcohol；2-[(1R,4R,4aS,8aS)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalen-1-yl]propan-1-ol
• CAS: 855425-50-2
• 化学式: C₁₅H₂₆O
• 分子量: 222.371
• InChiKey: SIKURLYPEUHJFQ-VBBGFSMDSA-N

物化性质

• 沸点：
  313.4±11.0 °C(Predicted)
• 密度：
  0.929±0.06 g/cm3(Predicted)
• 保留指数：
  1755

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  amorph-4-ene-12-ol 在 potassium tert-butylate 、 sodium iodide 作用下， 以 吡啶 、 丙酮 、 叔丁醇 为溶剂， 生成 amorpha-4,11-diene
  参考文献：
  名称：

  Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis

  摘要：

  The endoperoxide sesquiterpene lactone artemisinin and its derivatives are a promising new group of drugs against malaria. Artemisinin is a constituent of the annual herb Artemisia annua L. So far only the later steps in artemisinin biosynthesis - from artemisinic acid - have been elucidated and the expected olefinic sesquiterpene intermediate has never been demonstrated. In pentane extracts of A. annua leaves we detected a sesquiterpene with the mass spectrum of amorpha-4,11-diene. Synthesis of amorpha-4,11-diene from artemisinic acid confirmed the identity. In addition we identified several sesquiterpene synthases of which one of the major activities catalysed the formation of amorpha-4,11-diene from farnesyl diphosphate. This enzyme was partially purified and shows the typical characteristics of sesquiterpene syntheses, such as a broad pH optimum around 6.5-7.0, a molecular mass of 56 kDa, and a K-m of 0.6 mu M. The structure and configuration of amorpha-4,11-diene, its low content in A. annua and the high activity of amorpha-4,11-diene synthase all support that amorpha-4,11-diene is the likely olefinic sesquiterpene intermediate in the biosynthesis of artemisinin. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0031-9422(99)00206-x
• 作为产物：
  描述：

  methyl artemisinate 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 nickel dichloride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 14.0h， 生成 amorph-4-ene-12-ol
  参考文献：
  名称：

  质子和碳 13 核磁共振和一些紫杉烷（金好素衍生物）溶液中的构象

  摘要：

  报道了从巴西种植的青蒿中分离的青蒿素 I、II 和 V 以及合成衍生物青蒿素烯烃、酮和环氧树脂的总质子和碳 13 NMR 归属。这些化合物在溶液中的构象和构象平衡是从光谱数据和分子力学计算中获得的。

  DOI：

  10.1002/mrc.1260321004

文献信息

• Chemo- and Diastereoselective Hydrosilylation of Amorphadiene toward the Synthesis of Artemisinin
  作者：Geoffrey Schwertz、Andrea Zanetti、Marllon Nascimento de Oliveira、Mario Andrés Gomez Fernandez、Zacharias Amara、Janine Cossy

  DOI：10.1021/acs.joc.0c00617

  日期：2020.8.7

  A formal synthesis of artemisinin starting from amorphadiene is described. This new route relies on the development of a catalytic chemo- and diastereoselective hydrosilylation. The practicability of this method is demonstrated by converting amorphadiene to dihydroartemisinic aldehyde using a one-pot hydrosilylation/oxidation sequence, minimizing the number of purifications and maximizing the productivity

  描述了从吗啡二烯开始的青蒿素的正式合成。这种新途径依赖于催化化学和非对映选择性氢化硅烷化的发展。该方法的实用性通过使用一锅法氢化硅烷化/氧化顺序将吗啡二烯转化为二氢青蒿醛，通过一次实际的一锅法使纯化次数最少和生产率最大化来证明。此外，该方法可以与结晶诱导的非对映选择性转化（CIDT）结合使用，以增强关键目标中间体二氢青蒿醛的光学纯度。
• CONVERSION OF AMORPHA-4,11-DIENE TO ARTEMISININ AND ARTEMISININ PRECURSORS
  申请人：Reiling Kinkead Keith

  公开号：US20060270863A1

  公开（公告）日：2006-11-30

  The present invention relates to methods for the conversion of amorpha-4,11-diene to artemisinin and various artemisinin precursors.

  本发明涉及将阿莫非-4,11-二烯转化为青蒿素和各种青蒿素前体的方法。
• Proton and carbon-13 NMR and conformation in solution of some amorphanes (quinghaosu derivatives)
  作者：Anita J. Marsaioli、Fred Y. Fujiwara、Mary Ann Foglio、Nikolai Sharapin、Jin-Sheng Zhang

  DOI：10.1002/mrc.1260321004

  日期：1994.10

  The total proton and carbon‐13 NMR assignments of quinghaosu I, II and V isolated from Artemisia annua cultivated in Brazil and of the synthetic derivatives quinghaosu alkene, ketone and epoxy are reported. The conformations and conformational equilibria of these compounds in solution were obtained from the spectral data and molecular mechanics calculations.

  报道了从巴西种植的青蒿中分离的青蒿素 I、II 和 V 以及合成衍生物青蒿素烯烃、酮和环氧树脂的总质子和碳 13 NMR 归属。这些化合物在溶液中的构象和构象平衡是从光谱数据和分子力学计算中获得的。
• Identification of Intermediates and Enzymes Involved in the Early Steps of Artemisinin Biosynthesis in<i>Artemisia annua</i>
  作者：C. M. Bertea、J. R. Freije、H. van der Woude、F. W. Verstappen、L. Perk、V. Marquez、J-W. De Kraker、M. A. Posthumus、B. J. Jansen、Ae. de Groot、M. C. Franssen、H. J. Bouwmeester

  DOI：10.1055/s-2005-837749

  日期：2005.1

  An important group of antimalarial drugs consists of the endoperoxide sesquiterpene lactone artemisinin and its derivatives. Only little is known about the biosynthesis of artemisinin in Artemisia annua L., particularly about the early enzymatic steps between amorpha-4,11-diene and dihydroartemisinic acid. Analyses of the terpenoids from A. annua leaves and gland secretory cells revealed the presence of the oxygenated amorpha-4,11-diene derivatives artemisinic alcohol, dihydroartemisinic alcohol, artemisinic aldehyde, dihydroartemisinic aldehyde and dihydroartemisinic acid. We also demonstrated the presence of a number of biosynthetic enzymes such as the amorpha-4,11-diene synthase and the - so far unknown - amorpha-4,11-diene hydroxylase as well as artemisinic alcohol and dihydroartemisinic aldehyde dehydrogenase activities in both leaves and glandular trichomes. From these results, we hypothesise that the early steps in artemisinin biosynthesis involve amorpha-4,11-diene hydroxylation to artemisinic alcohol, followed by oxidation to artemisinic aldehyde, reduction of the C11-C13 double bond to dihydroartemisinic aldehyde and oxidation to dihydroartemisinic acid.

  一组重要的抗疟药物包括内酯倍半萜内酯青蒿素及其衍生物。人们对青蒿中青蒿素的生物合成知之甚少，尤其是对青蒿-4,11-二烯和二氢青蒿酸之间的早期酶解步骤知之甚少。对黄花蒿叶片和腺体分泌细胞中的萜类化合物进行分析后发现，其中存在含氧的 amorpha-4,11-二烯衍生物青蒿醇、二氢青蒿醇、青蒿醛、二氢青蒿醛和二氢青蒿酸。我们还证明了叶片和腺毛中存在多种生物合成酶，如青蒿-4,11-二烯合成酶和迄今未知的青蒿-4,11-二烯羟化酶，以及青蒿醇和二氢青蒿醛脱氢酶的活性。根据这些结果，我们推测青蒿素生物合成的早期步骤包括将 amorpha-4,11-二烯羟基化为青蒿醇，然后氧化为青蒿醛，将 C11-C13 双键还原为双氢青蒿醛，再氧化为双氢青蒿酸。
• Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis
  作者：Harro J. Bouwmeester、T.Eelco Wallaart、Michiel H.A. Janssen、Bert van Loo、Ben J.M. Jansen、Maarten A. Posthumus、Claus O. Schmidt、Jan-Willem De Kraker、Wilfried A. König、Maurice C.R. Franssen

  DOI：10.1016/s0031-9422(99)00206-x

  日期：1999.11

  The endoperoxide sesquiterpene lactone artemisinin and its derivatives are a promising new group of drugs against malaria. Artemisinin is a constituent of the annual herb Artemisia annua L. So far only the later steps in artemisinin biosynthesis - from artemisinic acid - have been elucidated and the expected olefinic sesquiterpene intermediate has never been demonstrated. In pentane extracts of A. annua leaves we detected a sesquiterpene with the mass spectrum of amorpha-4,11-diene. Synthesis of amorpha-4,11-diene from artemisinic acid confirmed the identity. In addition we identified several sesquiterpene synthases of which one of the major activities catalysed the formation of amorpha-4,11-diene from farnesyl diphosphate. This enzyme was partially purified and shows the typical characteristics of sesquiterpene syntheses, such as a broad pH optimum around 6.5-7.0, a molecular mass of 56 kDa, and a K-m of 0.6 mu M. The structure and configuration of amorpha-4,11-diene, its low content in A. annua and the high activity of amorpha-4,11-diene synthase all support that amorpha-4,11-diene is the likely olefinic sesquiterpene intermediate in the biosynthesis of artemisinin. (C) 1999 Elsevier Science Ltd. All rights reserved.