14β-hydroxy-2α,5α,10β-triacetoxy-4(20),11-taxadiene | 191536-23-9

• 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: 14β-hydroxy-2α,5α,10β-triacetoxy-4(20),11-taxadiene
• 英文别名: [(1S,2S,3S,5S,8S,10S,14S)-2,10-diacetyloxy-14-hydroxy-8,12,15,15-tetramethyl-4-methylidene-5-tricyclo[9.3.1.03,8]pentadec-11-enyl] acetate
• CAS: 191536-23-9
• 化学式: C₂₆H₃₈O₇
• 分子量: 462.584
• InChiKey: MBZPYSATAQTKSV-SFPMZPPXSA-N

物化性质

• 熔点：
  195 °C
• 沸点：
  522.5±50.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  14β-hydroxy-2α,5α,10β-triacetoxy-4(20),11-taxadiene 在 chromium(VI) oxide 、 叔丁基过氧化氢 、 偶氮二异丁腈 、 potassium tert-butylate 、 亚膦酸 、 sodium hydride 、 环己烯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 5α-hydroxy-2α,10β-diacetoxy-4(20),11-taxadien-13-one
  参考文献：
  名称：

  Synthesis and biological evaluation of taxinine analogues as orally active multidrug resistance reversal agents in cancer

  摘要：

  Three novel taxinine analogues were prepared and tested for their activity as multidrug resistance (MDR) reversal agents in comparison with verapamil. In vitro testing demonstrated that compounds 8-10 possess MDR-reversal activity in the KB/V cell line. Half-hour after treatment with 5, 10, and 20 mumol/L compound 9, the intracellular rhodamine 123 concentration increased 2.3, 2.9, and 3.2-fold, respectively, higher than 1.88-fold of 10 mumol/L verapamil in KB/V cell line. In vivo studies with VCR-resistant KB/V tumor xenografts showed that compound 9 in combination with VCR significantly inhibited tumor growth. Treatment with VCR or 9 alone did not result in growth inhibition. These results reveal that three taxinine analogues are good modifiers of MDR in tumor cells. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.089
• 作为产物：
  描述：

  taxuyunnanin C 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 以36%的产率得到14β-hydroxy-2α,5α,10β-triacetoxy-4(20),11-taxadiene
  参考文献：
  名称：

  Synthesis and structure–activity relationships of sinenxan A derivatives as multidrug resistance reversal agents

  摘要：

  Two types of sinenxan A derivatives with different side chains at C-5 were synthesized and evaluated for their in vitro multidrug resistant reversal activities. Several derivatives exhibited better activities than the positive control verapamil. The structure-activity relationships of these derivatives suggested that a carbonyl group at C-13 and the length of side chain at C-5 are important for the activity. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.099

文献信息

• Synthesis and structure–activity relationships of taxuyunnanine C derivatives as multidrug resistance modulator in MDR cancer cells
  作者：Toshiaki Hasegawa、Jiao Bai、Jungui Dai、Liming Bai、Junichi Sakai、Shigenori Nishizawa、Yuhua Bai、Midori Kikuchi、Mariko Abe、Takao Yamori、Akihiro Tomida、Takashi Tsuruo、Katsutoshi Hirose、Masayoshi Ando

  DOI：10.1016/j.bmcl.2007.04.030

  日期：2007.7

  the multidrug resistance of cancer cells. The cytotoxicity (IC(50)) of the compounds was examined against human normal cell line, WI-38, and cancer model cell lines, VA-13 and HepG2. Since compounds 6 and 8 had no cytotoxicity, they were expected to be lead compounds of MDR cancer reversal agents. On the contrary, compounds 3, 5, and 9a showed cell growth inhibitory activity toward VA-13 and/or HepG2

  通过对紫杉云南碱C进行化学修饰和生物转化，获得了一系列在不同位置（如C-2，C-5，C-7，C-9，C-10或C-14）带有较大基团的新一代紫杉类化合物（1 ）及其类似物4、5和10。化合物3、5、6、8和9a对MDR 2780AD细胞中的钙黄绿素蓄积具有显着的活性。实际上，最有效的化合物9a在C-14处具有肉桂酰氧基，在C-10处具有羟基，实际上对于MDR 2780AD细胞中抗癌剂长春新碱的细胞蓄积是有效的。6和9a对紫杉醇，阿霉素和长春新碱的增强作用与维拉帕米对MDR 2780AD细胞的增强作用相同。因此，化合物6和9a可以调节癌细胞的多药耐药性。检查了这些化合物对人正常细胞系的细胞毒性（IC（50）），WI-38和癌细胞模型VA-13和HepG2。由于化合物6和8没有细胞毒性，因此它们有望成为MDR癌症逆转剂的先导化合物。相反，化合物3、5和9a在MDR 2780AD中表现出对VA-
• Substrate specificity for the hydroxylation of polyoxygenated 4(20),11-taxadienes by Ginkgo cell suspension cultures
  作者：Jungui Dai、Min Ye、Hongzhu Guo、Weihua Zhu、Dayong Zhang、Qiu Hu、Junhua Zheng、Dean Guo

  DOI：10.1016/s0045-2068(03)00063-4

  日期：2003.8

  Three C-14 oxygenated taxanes isolated from callus cultures of Taxus spp., 2alpha,5alpha,10beta,14beta-tetra-acetoxy-4(20), 11-taxadiene 3, 2alpha,5alpha,10beta-triacetoxy-14beta-propionyloxy-4(20),11-taxadiene 4, 2alpha,5alpha,10beta-triacetoxy-14beta-(2-methylbutyryl)-oxy-4(20),I I-taxadiene 5, and three deacetylated derivatives of 3, 10beta-hydroxy-2alpha,5alpha,14beta-triacetoxy-4(20),11-taxadiene 6, 14beta-hydroxy-2alpha,5alpha, 10beta-triacetoxy-4(20),11-taxadiene 7, 10beta,14beta-dihydroxy-2alpha,5alpha-diacetoxy-4(20),11-taxadiene 8, could all be regio- and stereo-selectively hydroxylated at the 9alpha-position by Ginkgo cell suspension cultures to yield a series of new 9alpha,14beta-dihydroxylated taxoids. The effects of functional groups, especially at C-14 of the substrates, on the biotransformation were also investigated. The results revealed that substrates with an acetoxyl group at C-14 could be more efficiently 9alpha-hydroxylated than those with a longer ester chain or a hydroxyl group at C-14. An acetoxyl or hydroxyl group at C-10 had no effect on the conversion rates of the substrates, but substrates with the hydroxyl group (compared with the acetoxyl analogues) could be converted into 9alpha-hydroxylated products more easily. (C) 2003 Elsevier Science (USA). All rights reserved.
• 10.1002/anie.202407070
  作者：Li, Changkang、Yin, Xinxin、Wang, Shuai、Sui, Songyang、Liu, Jimei、Sun, Xincheng、Di, Jinming、Chen, Ridao、Chen, Dawei、Han, Yaotian、Xie, Kebo、Dai, Jungui

  DOI：10.1002/anie.202407070

  日期：——

  AbstractOxetane synthase (TmCYP1), a novel cytochrome P450 enzyme from Taxus×media cell cultures, has been functionally characterized to efficiently catalyse the formation of the oxetane ring in tetracyclic taxoids. Transient expression of TmCYP1 in Nicotiana benthamiana using 2α,5α,7β,9α,10β,13α‐hexaacetoxytaxa‐4(20),11(12)‐diene (1) as a substrate led to the production of a major oxetane derivative, 1β‐dehydroxybaccatin IV (1 a), and a minor 4β,20‐epoxide derivative, baccatin I (1 b). However, feeding the substrate decinnamoyltaxinine J (2), a 5‐deacetylated derivative of 1, yielded only 5α‐deacetylbaccatin I (2 b), a 4β,20‐epoxide. A possible reaction mechanism was proposed on the basis of substrate‐feeding, 2H and 18O isotope labelling experiments, and density functional theory calculations. This reaction could be an intramolecular oxidation‐acetoxyl rearrangement and the construction of the oxetane ring may occur through a concerted process; however, the 4β,20‐epoxide might be a shunt product. In this process, the C5‐O‐acetyl group in substrate is crucial for the oxetane ring formation but not for the 4(20)‐epoxy ring formation by TmCYP1. These findings provide a better understanding of the enzymatic formation of the oxetane ring in paclitaxel biosynthesis.
• Synthesis and structure–activity relationships of sinenxan A derivatives as multidrug resistance reversal agents
  作者：Meng Huang、Xin Zhao、Meng Zhang、Jun Gu、Xiaoguang Chen、Dali Yin

  DOI：10.1016/j.bmcl.2010.07.099

  日期：2010.9

  Two types of sinenxan A derivatives with different side chains at C-5 were synthesized and evaluated for their in vitro multidrug resistant reversal activities. Several derivatives exhibited better activities than the positive control verapamil. The structure-activity relationships of these derivatives suggested that a carbonyl group at C-13 and the length of side chain at C-5 are important for the activity. (c) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of taxinine analogues as orally active multidrug resistance reversal agents in cancer
  作者：Xin Zhao、Jun Gu、Dali Yin、Xiaoguang Chen

  DOI：10.1016/j.bmcl.2004.06.089

  日期：2004.9

  Three novel taxinine analogues were prepared and tested for their activity as multidrug resistance (MDR) reversal agents in comparison with verapamil. In vitro testing demonstrated that compounds 8-10 possess MDR-reversal activity in the KB/V cell line. Half-hour after treatment with 5, 10, and 20 mumol/L compound 9, the intracellular rhodamine 123 concentration increased 2.3, 2.9, and 3.2-fold, respectively, higher than 1.88-fold of 10 mumol/L verapamil in KB/V cell line. In vivo studies with VCR-resistant KB/V tumor xenografts showed that compound 9 in combination with VCR significantly inhibited tumor growth. Treatment with VCR or 9 alone did not result in growth inhibition. These results reveal that three taxinine analogues are good modifiers of MDR in tumor cells. (C) 2004 Elsevier Ltd. All rights reserved.