13-Acetyl-7-(triethylsilyl)baccatin III | 152448-78-7

• 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: 13-Acetyl-7-(triethylsilyl)baccatin III
• CAS: 152448-78-7
• 化学式: C₃₉H₅₄O₁₂Si
• 分子量: 742.936
• InChiKey: NHDSHLSYPSNUIW-HSXJCWEMSA-N

物化性质

• 沸点：
  722.1±60.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  52.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  160.96
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  13-Acetyl-7-(triethylsilyl)baccatin 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 15.0h， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12,15-triacetyloxy-1-hydroxy-10,14,17,17-tetramethyl-9-(2-naphthalen-2-yloxyacetyl)oxy-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 咪唑 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 13-Acetyl-7-(triethylsilyl)baccatin III
  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

文献信息

• New taxanes as highly efficient reversal agents for multi-drug resistance in cancer cells
  作者：Iwao Ojima、Pierre-Yves Bounaud、Craig Takeuchi、Paula Pera、Ralph J. Bernacki

  DOI：10.1016/s0960-894x(97)10218-9

  日期：1998.1

  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.
• Selective Deesterification Studies on Taxanes: Simple and Efficient Hydrazinolysis of C-10 and C-13 Ester Functionalities
  作者：Apurba Datta、Michael Hepperle、Gunda I. Georg

  DOI：10.1021/jo00108a053

  日期：1995.2
• Biocatalytic and Regioselective Exchange of 2‐O‐Benzoyl for 2‐O‐(m‐Substituted)Benzoyl Groups to Make Precursors of Next‐Generation Paclitaxel Drugs
  作者：Aimen Al‐Hilfi、Zhen Li、Kenneth M. Merz、Irosha N. Nawarathne、Kevin D. Walker

  DOI：10.1002/cctc.202400186

  日期：2024.5.8

  A taxane 2‐O‐benzoyltransferase (mTBT, derived from Accession: AF297618) biocatalyzed the dearoylation and rearoylation of next‐generation taxane precursors of drugs effective against multidrug‐resistant cancer cells. Various taxanes bearing an acyl, hydroxyl, or oxo group at C13 were screened to assess their turnover by mTBT catalysis. The 13‐oxotaxanes were the most productive, where 2‐O‐debenzoylation of 13‐oxobaccatin III was turned over faster compared to 13‐oxo‐10‐O‐(n‐propanoyl)‐10‐O‐deacetylbaccatin III and 13‐oxo‐10‐O‐(cyclopropane carbonyl)‐10‐O‐deacetylbaccatin III, yielding ~20 mg of each. mTBT catalysis was likely affected by an intramolecular hydrogen bond with the C13−hydroxyl. Oxidation to the 13‐oxo recovered catalysis. The experimental data for the debenzoylation reaction was supported by Gaussian‐accelerated molecular dynamics simulations that evaluated the conformational changes caused by different functional groups at C13 of the substrate. These findings also helped postulate where the 2‐O‐benzoylation reaction occurs on the paclitaxel pathway in nature. mTBT rearoylated the debenzoylated 13‐oxobaccatin III acceptors fastest with a non‐natural 3‐fluorobenzoyl CoA among the other aroyl CoA thioesters evaluated, yielding ~10 mg of each with excellent regioselectivity at laboratory scale. Reducing the 13‐oxo group to a hydroxyl yielded key modified baccatin III precursors (~10 mg at laboratory scale) of new‐generation taxoids.