[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-12-phenylmethoxycarbonyloxy-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate | 160237-44-5

• 英文名称: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-12-phenylmethoxycarbonyloxy-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 160237-44-5
• 化学式: C₄₃H₅₆O₁₂Si
• 分子量: 792.996
• InChiKey: HULGYZQFSNOVHZ-CNCBABBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.47
• 重原子数：
  56
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  164
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-12-phenylmethoxycarbonyloxy-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 在 palladium on activated charcoal 咪唑 、 硼烷四氢呋喃络合物 、 二乙胺基三氟化硫 、 氢气 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成
  参考文献：
  名称：

  New highly active taxoids from 9β-dihydrobaccatin-9,10-acetals. Part 2

  摘要：

  To investigate structure-activity relationships of the 9,10-acetal-9beta-dihydro taxoids, we modified the 7-hydroxyl groups of the 9,10-acetonide-3'-(4-pyridyl) analogue to deoxy, methoxy, alpha-F, and 7beta,8beta-methano group. As a result of this study, we found that the 7-deoxy analogue was the strongest among these analogues. In addition, we found that the 7-deoxy-3'-(4-pyridyl) and 7-deoxy-3'-(2-pyridyl) analogues showed stronger activity against cell lines expressing P-glycoprotein than the corresponding 3'-phenyl analogue. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00628-5
• 作为产物：
  描述：

  10-脱乙酰基巴卡丁 III 在 咪唑 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-12-phenylmethoxycarbonyloxy-9-triethylsilyloxy-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

文献信息

• Synthesis of new baccatin III derivatives through transesterification of β-keto esters with a protected 10-deacetylbaccatin III
  作者：Tadakatsu Mandai、Akiyoshi Kuroda、Hiroshi Okumoto、Katsuyoshi Nakanishi、Katsuhiko Mikuni、Ko-ji Hara、Ko-zo Hara

  DOI：10.1016/s0040-4039(99)02055-9

  日期：2000.1

  Synthesis of a new array of baccatin III derivatives bearing a β-keto ester appendage on C-13 is successfully achieved through transesterification of a wide range of β-keto esters with a protected baccatin III.

  通过将多种β-酮酯与受保护的浆果赤霉素III进行酯交换反应，成功地合成了一系列新的一系列浆果赤霉素III衍生物，它们在C-13上带有β-酮酯附件。
• A semisynthesis of paclitaxel via a 10-deacetylbaccatin III derivative bearing a β-keto ester appendage
  作者：Tadakatsu Mandai、Akiyoshi Kuroda、Hiroshi Okumoto、Katsuyoshi Nakanishi、Katsuhiko Mikuni、Ko-ji Hara、Ko-zo Hara

  DOI：10.1016/s0040-4039(99)02056-0

  日期：2000.1

  A semisynthesis of paclitaxel has successfully been accomplished starting from a newly developed baccatin III derivative bearing a β-keto ester appendage on C-13.

  从新开发的在C-13上带有β-酮酯附件的浆果赤霉素III衍生物开始成功地完成了紫杉醇的半合成。
• 一种7-三氯乙氧羰基多西他赛的制备方法
  申请人：无锡紫杉药业股份有限公司

  公开号：CN115197176A

  公开（公告）日：2022-10-18

  本发明公开了一种7‑三氯乙氧羰基多西他赛的制备方法，技术方案包括：S1：将10‑DAB、2‑甲基咪唑用DMF搅拌溶清，滴加三乙基氯硅烷反应，加水淬灭，得中间体I；S2：中间体I用四氢呋喃溶解，加入DMAP，滴加氯甲酸苄酯反应，得中间体II；S3：中间体II用吡啶溶清，加入氟化氢吡啶反应，加入二氯甲烷，滴加TrocCl反应，加水淬灭，得中间体III；S4：中间体III用甲苯溶解，加入多西侧链酸、DMAP和DCC反应，加水淬灭，加入盐酸反应，得中间体IV；S5：中间体IV用甲醇溶清，加入钯碳，密封后置换氮气三次，再置换为氢气，常压反应，纯化得目标产物；本发明的优点是通过选择性保护的方式定向得到各目标中间体，整体收率较高，分离难度较低，操作简易。