2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7-octahydronaphthalen-1-yl)propionic acid | 72807-99-9

• 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: 2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7-octahydronaphthalen-1-yl)propionic acid
• 英文别名: (2R)-2-[(1S,4R,4aS)-4-methyl-7-oxo-2,3,4,4a,5,6-hexahydro-1H-naphthalen-1-yl]propanoic acid
• CAS: 72807-99-9
• 化学式: C₁₄H₂₀O₃
• 分子量: 236.311
• InChiKey: XVDYCZISNDOFRJ-LSKIRQOJSA-N

物化性质

• 沸点：
  419.8±14.0 °C(predicted)
• 密度：
  1.12±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7-octahydronaphthalen-1-yl)propionic acid 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 (3R,3aS,6R,6aS,10aS)-3,6-dimethyl-3a,4,5,6,6a,7,8,10-octahydro-3H-benzo[h][1]benzofuran-2,9-dione
  参考文献：
  名称：

  二氢青蒿酸和二氢-的合成外延-deoxyarteannuin乙掺入稳定同位素标记的15位用于研究成青蒿素的生物合成

  摘要：

  [15- 13 c ^ 2 ^ h 3 ] -二氢青蒿酸（图3a）和[15- 13 CH 3 ]二氢外延-deoxyarteannuin B（图7b），用于评估在体内生物合成的前体青蒿素，已经从获得重建综合。青蒿素（1）的酸降解产生的十氢萘酮酸8用作常见的中间体：将标记的甲基格氏试剂添加到8中，可以通过改变所采用的后处理条件以高收率制备任何标记的前体。结果表明，两种化合物在储存时都易于自氧化，当用这些标记的前体在旨在确定青蒿中青蒿素生物合成途径的饲养实验中使用此类标记的前体时，这种氧化和随后的重排反应的产物可能与真正的代谢物混淆。

  DOI：

  10.1016/s0040-4020(01)00711-6
• 作为产物：
  描述：

  青蒿素 在 barium dihydroxide 、 硫酸 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 2-(4-methyl-7-oxo-(1α-H),2,3,(4β-H),(4aα-H),5,6,7-octahydronaphthalen-1-yl)propionic acid
  参考文献：
  名称：

  Epimerization in acid degradation products of artemisinin

  摘要：

  用酸处理青蒿素 1 可以得到环己烷二酮降解产物 10（这是研究青蒿素生物合成的有用中间体），也可以得到经过外延化的蜕皮素体系 8。核磁共振光谱、化学反应和分子建模表明，在表聚蜕皮素系列（8、17、14）中，笨重的 7-取代基采用轴向溶液构象，与该取代基为赤道构象的天然构型（11、15、13）相比，这种构象在热力学上更有利。相反，在环己烷二酮系列中，7-取代基为赤道型的天然构型更受青睐。本文讨论了这两个系列中存在不同构象偏好的原因，这些偏好最终导致了环化反应的发生，并介绍了一种用于识别环化产物的简单光谱程序。

  DOI：

  10.1039/a702714a

文献信息

• Synthesis of labelled dihydroartemisinic acid
  作者：Geoffrey D Brown、Lai-King Sy

  DOI：10.1016/j.tet.2003.11.069

  日期：2004.1

  [15-13C2H3]-Dihydroartemisinic acid (2a), [15-C2H3]-dihydroartemisinic acid (2b) and [15-13CH3]-dihydroartemisinic acid (2c) have been obtained in good yield and high isotopic enrichment by a reconstructive synthesis from artemisinin. These labelled compounds were designed to be used in biosynthetic experiments to determine the origins of artemisinin and other sesquiterpene natural products from Artemisia

  [15- 13 c ^ 2 ^ h 3 ] -二氢青蒿酸（图2a），[15-C 2 H ^ 3 ] -二氢青蒿酸（图2b）和[15- 13 CH 3 ] -二氢青蒿酸（2C）已经以良好的收率获得通过青蒿素的重组合成实现高同位素富集。这些标记的化合物被设计用于生物合成实验，以确定青蒿素和其他来自青蒿的倍半萜烯天然产物的来源。
• Design and Synthesis of Novel Artemisinin-Like Ozonides with Antischistosomal Activity
  作者：Zhong-Shun Yang、Wen-Min Wu、Ying Li、Yu-Lin Wu

  DOI：10.1002/hlca.200590229

  日期：2005.11

  artemisinin-like ozonides 10 were synthesized via a facile three-step procedure starting with the degraded product of artemisinin (Scheme). The Criegee ozonolysis reaction of the unsaturated lactone intermediates 14 is the key step which provided the target molecules 10. The in vivo pharmacological results suggested that this type of artemisinin analogues exhibited moderate antischistosomal activity (Table)

  开发用于血吸虫病预防和治疗新的药物，一系列新的青蒿素样臭氧化物10合成通过开始与青蒿素的降解产物（一个浅显三个步骤过程流程）。不饱和内酯中间体14的Criegee臭氧分解反应是提供目标分子10的关键步骤。在体内的药理结果表明，这种类型的青蒿素类似物表现出适度的抗血吸虫活性（表）。
• Design, Synthesis, and Pharmacological Evaluation of 2-(2,5-Dimethyl-5,6,7,8-tetrahydroquinolin-8-yl)-<i>N</i>-aryl Propanamides as Novel Smoothened (Smo) Antagonists
  作者：Gang Liu、Ding Xue、Jun Yang、Juan Wang、Xiaohua Liu、Wenjing Huang、Jie Li、Ya-Qiu Long、Wenfu Tan、Ao Zhang

  DOI：10.1021/acs.jmedchem.6b01247

  日期：2016.12.22

  A series of novel Smo antagonists were developed either by directly incorporating the basic skeleton of the natural product artemisinin or by first breaking artemisinin into structurally simpler and stable intermediates and then reconstructing into diversified heterocyclic derivatives, equipped with a Smo-targeting bullet. 2-(2,5-Dimethy1-5,6,7,8-tetrahydroquinolin-8-yl)-N-arylpropanamide 65 was identified as the most potent, with an IC50 value of 9.53 nM against the Hh signaling pathway. Complementary mechanism studies confirmed that 65 inhibits Hh signaling pathway by targeting Smo and shares the same binding site as that of the tool drug cyclopamine. Meanwhile, 65 has a good plasma exposure and an acceptable oral bioavailability. Dose-dependent antiproliferative effects were observed in ptch+/;p53-/- medulloblastoma cells, and significant tumor growth inhibitions were achieved for 65 in the ptch+/-;p53-/- medulloblastoma allograft model.
• Structure elucidation of arteannuin O, a novel cadinane diol from Artemisia annua, and the synthesis of arteannuins K, L, M and O
  作者：Lai-King Sy、Kung-Kai Cheung、Nian-Yong Zhu、Geoffrey D Brown

  DOI：10.1016/s0040-4020(01)00633-0

  日期：2001.10

  The novel cadinane diol, arteannuin O (1), has been obtained from Artemisia annua and its structure has been established by 2D NMR and X-ray crystallography. A reconstructive synthesis of arteannuin O from artemisinin is described, which also yields the natural products arteannuin K and arteannuin L. Mechanistic considerations have led to the conclusion that the stereochemistry of the 5-hydroxyl group was wrongly assigned when arteannuins K, L and M were first reported as natural products. This was confirmed by derivatization of synthetic arteannuins K, L and M as their Mosher esters. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Syntheses of dihydroartemisinic acid and dihydro-epi-deoxyarteannuin B incorporating a stable isotope label at the 15-position for studies into the biosynthesis of artemisinin
  作者：Lai-King Sy、Nian-Yong Zhu、Geoffrey D Brown

  DOI：10.1016/s0040-4020(01)00711-6

  日期：2001.10

  [15-13C2H3]-Dihydroartemisinic acid (3a) and [15-13CH3]-dihydro-epi-deoxyarteannuin B (7b), intended for evaluation in vivo as biosynthetic precursors to artemisinin, have been obtained from a reconstructive synthesis. The decalenone acid 8 from acid degradation of artemisinin (1) serves as a common intermediate: following addition of labeled methyl Grignard reagent to 8, either labeled precursor can

  [15- 13 c ^ 2 ^ h 3 ] -二氢青蒿酸（图3a）和[15- 13 CH 3 ]二氢外延-deoxyarteannuin B（图7b），用于评估在体内生物合成的前体青蒿素，已经从获得重建综合。青蒿素（1）的酸降解产生的十氢萘酮酸8用作常见的中间体：将标记的甲基格氏试剂添加到8中，可以通过改变所采用的后处理条件以高收率制备任何标记的前体。结果表明，两种化合物在储存时都易于自氧化，当用这些标记的前体在旨在确定青蒿中青蒿素生物合成途径的饲养实验中使用此类标记的前体时，这种氧化和随后的重排反应的产物可能与真正的代谢物混淆。