2α,5α,10β-triacetoxy-4(20),11-taxadien-13-one | 444307-64-6

• 英文名称: 2α,5α,10β-triacetoxy-4(20),11-taxadien-13-one
• 英文别名: [(1R,2R,3S,5S,8S,10S)-2,10-diacetyloxy-8,12,15,15-tetramethyl-4-methylidene-13-oxo-5-tricyclo[9.3.1.03,8]pentadec-11-enyl] acetate
• CAS: 444307-64-6
• 化学式: C₂₆H₃₆O₇
• 分子量: 460.568
• InChiKey: PQWUEVXGQMOQTG-JTELSQPYSA-N

物化性质

• 熔点：
  72-74 °C
• 沸点：
  529.7±50.0 °C(predicted)
• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  96
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2α,5α,10β-triacetoxy-4(20),11-taxadien-13-one 在 吡啶 、 4-二甲氨基吡啶 、 四氧化锇 、 potassium tert-butylate 、 potassium carbonate 、 N-甲基吗啉氧化物 、 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 、 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 33.0h， 生成 5β,20-epoxy-2α,4α,10β-triacetoxy-11-taxen-13-one
  参考文献：
  名称：

  Synthesis of 7,9-dideoxybaccatin IV analogs from sinenxan A

  摘要：

  Sinenxan A, a taxoid isolated from callus tissue cultures of Taxus yunnanensis was converted into 13-oxo-7,9-dideoxy-2-debenzoyl-2-acetyl-baccatin IV and 7.9-dideoxy-2-debenzoyl-4-deacetyl-baccatin IV, a key framework of 1,7,9-trideoxypaclitaxel. Several special steps in this transformation are worthy of note: (1) deoxygenation by treatment with hypophosphorous acid at C-14 positions (2) a highly regioselective O-deacetylation of taxane:, at C-5 position; and (3) stereoselective reduction of the 13-carbonyl group by transannular assistance from the C-4-hydroxyl. (c) 2005 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2005.03.137
• 作为产物：
  描述：

  4β-S-methyl-dithiocarboxy-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 、 亚膦酸 、 环己烯 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 2α,5α,10β-triacetoxy-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

文献信息

• Synthetic study of 1,7,9-trideoxypaclitaxel via sinenxan A
  作者：Meng Zhang、Dali Yin、Ji-Yu Guo、Xiao-Tian Liang

  DOI：10.1016/s0040-4039(02)02330-4

  日期：2002.12

  Sinenxan A, a biosynthetic taxane, was converted into compound 9, a key intermediate of 1,7,9-trideoxypaclitaxel. Two special steps in this transformation are worthy of note: (1) regioselective removal of C-5-acetyl; and (2) stereoselective reduction of the 13-carbonyl group by transannular assistance from the C-4-hydroxyl. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 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.
• A Cytochrome P450 Enzyme Catalyses Oxetane Ring Formation in Paclitaxel Biosynthesis
  作者：Changkang Li、Xinxin Yin、Shuai Wang、Songyang Sui、Jimei Liu、Xincheng Sun、Jinming Di、Ridao Chen、Dawei Chen、Yaotian Han、Kebo Xie、Jungui Dai

  DOI：10.1002/anie.202407070

  日期：2024.7.29

  Oxetane 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.