9α,10β-dihydroxy-2α-acetoxy-5α-cinnamoyloxy-taxa-4(20),11-dien-13-one | 15135-57-6

• 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: 9α,10β-dihydroxy-2α-acetoxy-5α-cinnamoyloxy-taxa-4(20),11-dien-13-one
• 英文别名: 2α-acetoxy-5α-cinnamoyloxy-9α,10β-dihydroxytaxa-4(20),11-dien-13-one；[(1R,2R,3R,5S,8R,9R,10R)-2-acetyloxy-9,10-dihydroxy-8,12,15,15-tetramethyl-4-methylidene-13-oxo-5-tricyclo[9.3.1.03,8]pentadec-11-enyl] (E)-3-phenylprop-2-enoate
• CAS: 15135-57-6
• 化学式: C₃₁H₃₈O₇
• 分子量: 522.639
• InChiKey: VINWCUNFNJBSQA-IRZWYNESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9α,10β-dihydroxy-2α-acetoxy-5α-cinnamoyloxy-taxa-4(20),11-dien-13-one 在 吡啶 、 4-二甲氨基吡啶 、 氢氧化钾 、 四氧化锇 、 N-甲基吲哚酮 、 盐酸羟胺 、 四丁基氟化铵 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 生成 2α-benzoyloxy-5β,20-epoxy-4α-hydroxy-9α,10β-isopropylidenedioxy-11-taxen-13-one
  参考文献：
  名称：

  Structure–activity relationships of some taxoids as multidrug resistance modulator

  摘要：

  1,7-Deoxy-4-deacetylbaccatin III (12) and its five analogues 6-9, 13, and their oxetane ring opened derivatives 14, 16, and 17, which were synthesized from taxinine, showed significant activity as MDR reversal agent by the assay of the calcein accumulation toward MDR human ovarian cancer 2780AD cells. The most effective compound 12 in this assay is actually efficient for the recovery of cytotoxic activity of paclitaxel (taxol), adriamycin (ADM), and vincristine (VCR) toward MDR 2780AD cells at the same level toward parental 2780 cells. This activity of 12 is very interesting because baccatin 111 (4) has no such MDR reversal activity but has cytotoxic activity. The essential functional groups inducing such a difference in biological activity between 4 and 12 are 4 alpha-acetoxyl for 4 and 4 alpha-hydroxyl for 12. In seven compounds possessing MDR reversal activity, compound 12 is the most desirable compound for anti-MDR cancer reversal agent, because it has the highest accumulation ability of anticancer agent in MDR cancer cells and weak cytotoxic activity. Compounds 8 and 13 showed significant cytotoxic activity toward HepG2 and VA-13, respectively, as well as MDR reversal activity. They are expected to become lead compounds for new types of anticancer agent or anti-MDR cancer agent. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.068
• 作为产物：
  描述：

  紫杉宁 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 以92%的产率得到9α,10β-dihydroxy-2α-acetoxy-5α-cinnamoyloxy-taxa-4(20),11-dien-13-one
  参考文献：
  名称：

  Structure–activity relationships of some taxoids as multidrug resistance modulator

  摘要：

  1,7-Deoxy-4-deacetylbaccatin III (12) and its five analogues 6-9, 13, and their oxetane ring opened derivatives 14, 16, and 17, which were synthesized from taxinine, showed significant activity as MDR reversal agent by the assay of the calcein accumulation toward MDR human ovarian cancer 2780AD cells. The most effective compound 12 in this assay is actually efficient for the recovery of cytotoxic activity of paclitaxel (taxol), adriamycin (ADM), and vincristine (VCR) toward MDR 2780AD cells at the same level toward parental 2780 cells. This activity of 12 is very interesting because baccatin 111 (4) has no such MDR reversal activity but has cytotoxic activity. The essential functional groups inducing such a difference in biological activity between 4 and 12 are 4 alpha-acetoxyl for 4 and 4 alpha-hydroxyl for 12. In seven compounds possessing MDR reversal activity, compound 12 is the most desirable compound for anti-MDR cancer reversal agent, because it has the highest accumulation ability of anticancer agent in MDR cancer cells and weak cytotoxic activity. Compounds 8 and 13 showed significant cytotoxic activity toward HepG2 and VA-13, respectively, as well as MDR reversal activity. They are expected to become lead compounds for new types of anticancer agent or anti-MDR cancer agent. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.068

文献信息

• Syntheses of Taxuspine C Derivatives as Functional Inhibitors of P-Glycoprotein, an ATP-Associated Cell-Membrane Transporter.
  作者：Magoichi SAKO、Hikokazu SUZUKI、Kosaku HIROTA

  DOI：10.1248/cpb.46.1135

  日期：——

  UV-Irradiation of taxinine and related compounds in acetonitrile induced a smooth transannulation between the C-3 and C-11 positions without any influence from the C-2, C-9 and C-10 substituents to give tetracyclic taxuspine C derivatives in almost quantitative yields. Photochemical transannular reaction of taxoids possessing a cinnamoyl group in the side-chain was accompanied by an E,Z-isomerization

  在乙腈中紫外线照射紫杉碱及相关化合物可诱导C-3和C-11位置之间平稳过渡，而不受C-2，C-9和C-10取代基的影响，从而得到几乎定量的四环紫杉烷C衍生物产量。在侧链上具有肉桂酰基的紫杉烷类化合物的光化学跨环反应伴随着肉桂酰基部分的E，Z-异构化。发现长春新碱（一种对癌症化疗有用的药物）在具有多重耐药性的卵巢癌细胞中的细胞蓄积最有效地增加了5-O-苯甲酰化的5-O-癸氨酰紫杉醇C的含量。这表明5-O-苯甲酰化的红豆杉C衍生物可能是有前途的P糖蛋白功能抑制剂，它可作为癌症化疗药物的ATP相关外排泵。
• A taxane-11,12-oxide from Taxus yunnanensis
  作者：Qin Yue、Qi-Cheng Fang、Xiao-Tian Liang

  DOI：10.1016/0031-9422(96)00299-3

  日期：1996.10

  Abstract A new taxoid, decinnamoyl-taxinine B-11,12-oxide, was isolated from the leaves and stems of Taxus yunnanensis . This is the first example of an 11,12-epoxy taxoid isolated from the yew tree.

  摘要 从云南红豆杉的叶和茎中分离到了一种新的紫杉类，癸二酰紫杉碱B-11,12-氧化物。这是从紫杉树中分离出的 11,12-环氧紫杉醇的第一个例子。
• An Efficient Conversion of Taxinine to Taxinine NN-1, an Anticancer Agent and a Modulator of Multidrug-Resistant Tumor Cells
  作者：Shujun Zhang、Jinlan Wang、Katutoshi Hirose、Masayoshi Ando

  DOI：10.1021/np020240n

  日期：2002.12.1

  Taxinine NN-1 (1), which shows significant activities as a modulator of multidrug-resistant cancer cells and as an anticancer agent in an in vitro assay based on a HCC panel, was synthesized in order to obtain sufficient material for a higher order bioassay from easily available taxinine (2). The synthesis was achieved via intermediate 8, which was derived from 2 by the stepwise protection of a 9, 10-dihydroxyl group as acetonide and a 2-hydroxyl group as a MOM protecting group. The temporary elimination of a cinnamoyl group at C-5 of 8 and successive reduction of a C-13 carbonyl group of the resulting 9 gave 10 and the undesired 13-epimer 11. The latter was recycled to 9 by oxidation with MnO2. Stepwise acetylation and cinnamoylation at C-13 and C-5 of 10 and successive deprotection of the acetonide protecting group at C-9,10 of the resulting 13 gave diol 14. Diacetylation of 14 and deprotection of the MOM protecting group at C-2 of the resulting 15 gave 1. The overall yield of 1 was 45% in 11 steps from 2.
• Sako, Magoichi; Suzuki, Hikokazu; Yamamoto, Noriyuki, Journal of the Chemical Society. Perkin transactions I, 1998, # 3, p. 417 - 421
  作者：Sako, Magoichi、Suzuki, Hikokazu、Yamamoto, Noriyuki、Hirota, Kosaku、Maki, Yoshifumi

  DOI：——

  日期：——
• Structure–activity relationships of some taxoids as multidrug resistance modulator
  作者：Toshiaki Hasegawa、Jao Bai、Shujun Zhang、Jinlan Wang、Junichi Matsubara、Junichi Kawakami、Akihiro Tomida、Takashi Tsuruo、Katsutoshi Hirose、Junichi Sakai、Midori Kikuchi、Mariko Abe、Masayoshi Ando

  DOI：10.1016/j.bmcl.2006.09.068

  日期：2007.2

  1,7-Deoxy-4-deacetylbaccatin III (12) and its five analogues 6-9, 13, and their oxetane ring opened derivatives 14, 16, and 17, which were synthesized from taxinine, showed significant activity as MDR reversal agent by the assay of the calcein accumulation toward MDR human ovarian cancer 2780AD cells. The most effective compound 12 in this assay is actually efficient for the recovery of cytotoxic activity of paclitaxel (taxol), adriamycin (ADM), and vincristine (VCR) toward MDR 2780AD cells at the same level toward parental 2780 cells. This activity of 12 is very interesting because baccatin 111 (4) has no such MDR reversal activity but has cytotoxic activity. The essential functional groups inducing such a difference in biological activity between 4 and 12 are 4 alpha-acetoxyl for 4 and 4 alpha-hydroxyl for 12. In seven compounds possessing MDR reversal activity, compound 12 is the most desirable compound for anti-MDR cancer reversal agent, because it has the highest accumulation ability of anticancer agent in MDR cancer cells and weak cytotoxic activity. Compounds 8 and 13 showed significant cytotoxic activity toward HepG2 and VA-13, respectively, as well as MDR reversal activity. They are expected to become lead compounds for new types of anticancer agent or anti-MDR cancer agent. (c) 2006 Elsevier Ltd. All rights reserved.