2-[1-(butyryloxy)-4-methyl-3-pentenyl]naphthazarin

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[1-(butyryloxy)-4-methyl-3-pentenyl]naphthazarin
• 英文别名: butylshikonin；[(1R)-1-(5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] butanoate
• 化学式: C₂₀H₂₂O₆
• 分子量: 358.391
• InChiKey: FMXUZLUFNDEQPM-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  乙酰紫草素 在 4-二甲氨基吡啶 、 sodium hydroxide 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 2-[1-(butyryloxy)-4-methyl-3-pentenyl]naphthazarin
  参考文献：
  名称：

  Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon

  摘要：

  Three naphthoquinones were isolated by bioassay-guided fractionation from the CHCl3 extracts of roots of Lithospermum erythrorhizon. They were identified as acetylshikonin (1), isobutyrylshikonin (2), and (3-hydroxyisovalerylshikonin (3) on the basis of their spectroscopic analyses. The compounds 1-3 were tested for their inhibitory activities against human ACAT-1 (hACAT-1) or human ACAT-2 (hACAT-2). Compound 2 preferentially inhibited hACAT-2 (IC50 = 57.5 wM) than hACAT-1 (32% at 120 mu M), whereas compounds 1 and 3 showed weak inhibitory activities in both hACAT-1 and -2. To develop more potent hACAT inhibitor, shikonin derivatives (5-11) were synthesized by semi-synthesis of shikonin (4), which was prepared by hydrolysis of 1-3. Among them, compounds 5 and 7 exhibited the strong inhibitory activities against hACAT-1 and -2. Furthermore, we demonstrated that compound 7 behaved as a potent ACAT inhibitor in not only in vitro assay system but also cell-based assay system. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.024

文献信息

• Design and Synthesis of Fluoroacylshikonin as an Anticancer Agent
  作者：Wen-Yao Kong、Xiao-Feng Chen、Jing Shi、Shahla Karim Baloch、Jin-Liang Qi、Hai-Liang Zhu、Xiao-Ming Wang、Yong-Hua Yang

  DOI：10.1002/chir.22209

  日期：2013.11

  selectively acylated by various fluorinated carboxylic acids at the side chain of shikonin, were synthesized and their anticancer activity evaluated, in which eight compounds are reported for the first time. Among all the compounds tested, compound S7 showed the most potent anticancer activity against B16‐F10 (malignant melanoma cells), MG63 (human osteosarcoma cells), and A549 (lung cancer cells) with

  合成了一系列在紫草素侧链上被各种氟化羧酸选择性酰化的紫草素衍生物，并对其抗癌活性进行了评估，其中首次报道了八种化合物。在所有测试的化合物中，化合物S7对B16-F10（恶性黑色素瘤细胞），MG63（人骨肉瘤细胞）和A549（肺癌细胞）显示出最有效的抗癌活性，IC 50为0.39±0.01、0.72±0.04和0.58 ±0.02 µmol / L。进行化合物S7的对接模拟以将S7定位在微管蛋白活性位点，以确定可能的结合构象。所有结果表明，化合物S7可能是潜在的抗癌药。手性25：757–762，2013。©2013 Wiley Periodicals，Inc.
• Acylshikonin Analogs: Synthesis and Inhibition of DNA Topoisomerase-I
  作者：Byung-Zun Ahn、Kyong-Up Baik、Gi-Ryang Kweon、Kyu Lim、Byung-Doo Hwang

  DOI：10.1021/jm00006a025

  日期：1995.3

  Compounds bearing an acyl group of a various size at 1'-OH of shikonin were synthesized as acyl analogues of shikonin, which was isolated from the root of Lithospermum erythrorhizon, and evaluated for inhibitory effect on topoisomerase-I activity. A selective acylation at 1'-OH of shikonin in the presence of dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine gave rise to a good yield of corresponding acylshikonin derivatives. In general, analogues with an acyl group of shorter chain lengths (C-2-C-6) exerted a stronger inhibitory action than those with longer chain lengths (C-7-C-20). While the halogen substitution at C-2 of the acetyl moiety failed to increase the inhibitory potency, the placement of double bonds in the acyl group (C-5-C-7) augmented the potency remarkably. Of the 32 derivatives evaluated, 15 compounds exhibited a higher inhibitory effect than shikonin. Noteworthy, the inhibitory potency of acetylshikonin, propanoylshikonin, and 4-pentenoylshikonin was approximately 4-fold greater than that of camptothecin. All these data suggest that the size of acyl moiety is important for the enhancement of potency, and the presence of olefinic double bonds is also beneficial.
• Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon
  作者：Sojin An、Yong-Dae Park、Young-Ki Paik、Tae-Sook Jeong、Woo Song Lee

  DOI：10.1016/j.bmcl.2006.11.024

  日期：2007.2

  Three naphthoquinones were isolated by bioassay-guided fractionation from the CHCl3 extracts of roots of Lithospermum erythrorhizon. They were identified as acetylshikonin (1), isobutyrylshikonin (2), and (3-hydroxyisovalerylshikonin (3) on the basis of their spectroscopic analyses. The compounds 1-3 were tested for their inhibitory activities against human ACAT-1 (hACAT-1) or human ACAT-2 (hACAT-2). Compound 2 preferentially inhibited hACAT-2 (IC50 = 57.5 wM) than hACAT-1 (32% at 120 mu M), whereas compounds 1 and 3 showed weak inhibitory activities in both hACAT-1 and -2. To develop more potent hACAT inhibitor, shikonin derivatives (5-11) were synthesized by semi-synthesis of shikonin (4), which was prepared by hydrolysis of 1-3. Among them, compounds 5 and 7 exhibited the strong inhibitory activities against hACAT-1 and -2. Furthermore, we demonstrated that compound 7 behaved as a potent ACAT inhibitor in not only in vitro assay system but also cell-based assay system. (c) 2006 Elsevier Ltd. All rights reserved.