13-acetylbaccatin III | 76446-91-8

• 英文名称: 13-acetylbaccatin III
• 英文别名: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12,15-triacetyloxy-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 76446-91-8
• 化学式: C₃₃H₄₀O₁₂
• 分子量: 628.673
• InChiKey: CIUIETSAKZWPII-UVDWMJHKSA-N

物化性质

• 沸点：
  708.7±60.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  172
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  13-acetylbaccatin III 在 吡啶 、 4-二甲氨基吡啶 、 氟化氢吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 21.0h， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12,15-triacetyloxy-1-hydroxy-9-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]oxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  Design, Synthesis and Structure−Activity Relationships of Novel Taxane-Based Multidrug Resistance Reversal Agents

  摘要：

  A series of novel taxane-based multidrug resistance (MDR) reversal agents (TRAs) has been designed and synthesized. Structure-activity relationship (SAR) study clearly indicates that modification of the C-7 position with hydrophobic arenecarbonyleinnamoyl groups brings about high potency against drug efflux mediated by P-glycoprotein (P-gp). Six TRAs exhibit ability to modulate a wide range of ATP-binding cassette (ABC) transporters, such as P-gp, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP), which may serve as novel broad-spectrum modulators of ABC transporters.

  DOI：

  10.1021/jm049483y
• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 吡啶 、 4-二甲氨基吡啶 、 氟化氢吡啶 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 13-acetylbaccatin III
  参考文献：
  名称：

  New taxanes as highly efficient reversal agents for multi-drug resistance in cancer cells

  摘要：

  New non-cytotoxic taxanes synthesized from 10-deacetylbaccatin III and special hydrophobic acylating agents show remarkable MDR reversal activity (less than or equal to 99.8%) against drug-resistant human breast cancer cells when co-administered with paclitaxel or doxorubicin. This activity is ascribed to the highly efficient blocking of P-glycoprotein efflux by these new taxanes. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)10218-9

文献信息

• The Taxol Pathway 10-<i>O</i>-Acetyltransferase Shows Regioselective Promiscuity with the Oxetane Hydroxyl of 4-Deacetyltaxanes
  作者：Mark E. Ondari、Kevin D. Walker

  DOI：10.1021/ja8067534

  日期：2008.12.17

  revealed the taxane 10beta-O-acetyltransferase was able to catalyze the 4-O-acetylation of 4-deacetylbaccatin III to baccatin III and 13-acetyl-4-deacetylbacatin III to 13-acetylbaccatin III, although each was converted at lesser efficiency than with the natural substrate. In contrast, this enzyme was unable to acetylate 7-acetyl-4-deacetylbaccatin III and 7,13-diacetyl-4-deacetylbaccatin III substrates

  10-脱乙酰浆果赤霉素 III: 10beta-O-乙酰转移酶从红豆杉 regiospecifically 转移短链烷酰基组从其相应的 CoA 硫酯转移到 10-脱乙酰浆果赤霉素 III 的 C10 羟基。这种 10-O-乙酰转移酶与紫杉醇 (Taxol) 生物合成途径上的其他五种红豆杉酰基转移酶和一种额外的未知功能的红豆杉衍生的酰基转移酶一起筛选了针对 4-脱乙酰浆果赤霉素 III、7-乙酰基转移酶的 4-O-乙酰转移酶活性， 13-乙酰基-和 7,13-二乙酰基-4-脱乙酰基浆果赤霉素 III。这些 4-脱酰基衍生物是从天然产物浆果赤霉素 III 通过甲硅烷基保护基操作、双（2-甲氧基乙氧基）氢化铝钠的区域选择性还原酯裂解和乙酸酐的区域选择性乙酰化半合成的。对 4-脱乙酰二萜底物和乙酰辅酶 A 的分析表明紫杉烷 10β-O-乙酰转移酶能够催化 4-脱乙酰浆果赤霉素 III 的 4-O-乙酰化为浆果赤霉素
• Conversion of 9-dihydro-13-acetylbaccatin III to baccatin III and 10-deacetyl baccatin III
  申请人：——

  公开号：US20010041803A1

  公开（公告）日：2001-11-15

  Novel methods and synthetic intermediates to prepare baccatin III and 10-deacetylbaccatin from readily available 9-dihydro-13-acetylbaccatin III are described. Selective protection and deprotection of the C-7 hydroxyl functionality provides an entry into facile synthesis of novel taxol intermediates, as well as, providing new methods for the preparation of paclitaxel and docetaxel in large scale. Selective oxidation of the C-9 hydroxyl without the need for protection of the C-7 hydroxyl is described.

  本文介绍了从易得的9-二氢-13-乙酰基紫杉醇III制备紫杉醇III和10-脱乙酰基紫杉醇的新方法和合成中间体。选择性保护和去保护C-7羟基官能团提供了进入新型紫杉醇中间体的易于合成的途径，同时也提供了大规模制备紫杉醇和多西他赛的新方法。本文还介绍了不需要保护C-7羟基官能团的选择性氧化C-9羟基的方法。
• Targeting FtsZ for Antituberculosis Drug Discovery:  Noncytotoxic Taxanes as Novel Antituberculosis Agents
  作者：Qing Huang、Fumiko Kirikae、Teruo Kirikae、Antonella Pepe、Amol Amin、Laurel Respicio、Richard A. Slayden、Peter J. Tonge、Iwao Ojima

  DOI：10.1021/jm050920y

  日期：2006.1.1

  Screening of 120 taxanes identified a number of compounds that exhibited significant antituberculosis activity. Rational optimization of selected compounds led to the discovery that the C-seco-taxane-multidrug-resistance (MDR) reversal agents (C-seco-TRAs) are non-cytotoxic at the upper limit of solubility and detection (> 80 mu M), while maintaining MIC99 values of 1.25-2.5 mu M against drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis (MTB). Treatment of MTB cells with TRA 3aa and 10a at the MIC caused filamentation and prolongation of the cells, a phenotypic response to FtsZ inactivation.
• Taxus canadensis abundant taxane: conversion to paclitaxel and rearrangements
  作者：Anastasia Nikolakakis、Gaétan Caron、Alice Cherestes、Françoise Sauriol、Orval Mamer、Lolita O Zamir

  DOI：10.1016/s0968-0896(00)00056-0

  日期：2000.6

  An efficient conversion of Taxus canadensis abundant taxane, 9-dihydro-13-acetylbaccatin III to baccatin III is described. Since the synthesis of paclitaxel from baccatin III has been reported, this work can be used for additional supply of this powerful anticancer drug. In addition, new taxanes derived from skeletal rearrangements originating from oxidation-reduction reactions of the Canadian yew major taxane, are reported. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Modified taxols. 3. Preparation and acylation of baccatin III
  作者：Neal F. Magri、David G. I. Kingston、Chote Jitrangsri、Thomas Piccariello

  DOI：10.1021/jo00366a043

  日期：1986.8