10-deacetoxy-paclitaxel | 148121-24-8

• 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: 10-deacetoxy-paclitaxel
• 英文别名: 10-deacetoxypaclitaxel；10-deacetoxytaxol；10-deacetylpaclitaxel；10-desacetoxytaxol；[(1S,2S,3R,4S,7R,9S,10S,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-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: 148121-24-8
• 化学式: C₄₅H₄₉NO₁₂
• 分子量: 795.884
• InChiKey: JKUFNLVYPRJLGU-XAOCBTQESA-N

物化性质

• 沸点：
  930.3±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  58
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  195
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  10-deacetoxy-paclitaxel 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 N-甲基吲哚酮 、 四丙基高钌酸铵 、 4 A molecular sieve 、 氢氟酸 、 双(三甲基硅烷基)氨基钾 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 51.0h， 生成
  参考文献：
  名称：

  Synthesis of a novel C-10 spiro-epoxide of paclitaxel

  摘要：

  New analogues of paclitaxel (1a, active constituent of Taxol((R))) were synthesized containing an epoxide at the C-10 position. The introduction of the epoxide was carried out by selective removal of the C10-acetate followed by protection of the C2 ' -and C7-hydroxyl groups. After oxidation to yield a ketone at the C10-position, this intermediate was reacted with dimethylsulfonium ylide. Deprotection and further manipulations provide the C10-spiro epoxide of paclitaxel (1b) and the corresponding C7-MOM ether (1c). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00280-3
• 作为产物：
  描述：

  紫杉醇 在 samarium diiodide 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 0.17h， 以90%的产率得到10-deacetoxy-paclitaxel
  参考文献：
  名称：

  紫杉烷二萜的化学：10-脱乙酰氧基-11,12-环氧紫杉醇的立体选择性合成

  摘要：

  用间氯过苯甲酸完成10-deacetoxybaccatin III（6）和10-deacetoxypaclitaxel（9）中烯烃的环氧化反应，产生了新的五环体系。由于在分子的β-面发生环氧化，因此环氧直接引导的环氧化剂似乎没有在反应的立体选择性中起作用。在微管组装试验中，10 -Deacetoxy-11,12-epoxypaclitaxel（10）比紫杉醇（1）更具活性，对紫杉醇对B16黑色素瘤细胞的毒性比紫杉醇低三倍。

  DOI：

  10.1016/0040-4039(95)01928-b

文献信息

• Process for the preparation of baccatin III analogs bearing new C2 and C4 functional groups
  申请人：Florida State University

  公开号：US06727369B1

  公开（公告）日：2004-04-27

  Process for the preparation of a derivative or analog of baccatin III or 10-desacetyl baccatin III having a C2 substituent other than benzoate and/or a C4 substituent other than acetate in which the C2 benzoate substituent and/or the C4 acetate substituent of a derivative of baccatin III or 10-desacetyl baccatin III is/are selectively reduced to the corresponding hydroxy group(s) and converted to R7COO— and/or R8COO—, respectively, wherein R7 and R8 are independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C8 alkynyl, moncyclic aryl, or monocyclic heteroaryl.

  这段文字是关于制备紫杉醇前体化合物——特别是baccatin III或10-desacetyl baccatin III的衍生物或类似物——的化学工艺描述。该工艺涉及对baccatin III或10-desacetyl baccatin III的C2位置上的苯甲酸酯基团和/或C4位置上的醋酸酯基团进行选择性还原，将它们转化为相应的羟基，并进一步转化为R7COO—和/或R8COO—，其中R7和R8独立地代表氢、C1-C6烷基、C2-C6烯基、C2-C8炔基、单环芳基或单环杂芳基。以下是中文翻译： 制备baccatin III或10-去乙酰基baccatin III的衍生物或类似物的工艺，该衍生物或类似物具有除苯甲酸酯以外的C2取代基和/或除醋酸酯以外的C4取代基，其中baccatin III或10-去乙酰基baccatin III衍生物的C2位苯甲酸酯取代基和/或C4位醋酸酯取代基被选择性地还原为相应的羟基，并且分别转化为R7COO—和/或R8COO—，其中R7和R8独立地为H，C1-C6烷基，C2-C6烯基，C2-C8炔基，单环芳基或单环杂芳基。
• Synthesis of 10-deacetoxytaxol and 10-deoxytaxotere
  作者：Ashok G. Chaudhary、David G.I. Kingston

  DOI：10.1016/s0040-4039(00)74046-9

  日期：1993.7

  10-Deacetoxytaxol (9) and 10-deoxytaxotere (10) have been prepared from 10-deacetylbaccatin III by attachment of the C-13 side-chain and deoxygenation. 10-Deacetoxytaxol is comparable to taxol in its cytotoxicity to P-388 cells, but 10-deoxytaxotere is significantly more cytotoxic than taxol.

  10-脱乙酰基紫杉醇（9）和10-脱氧紫杉醇（10）已经通过连接C-13侧链和脱氧由10-脱乙酰基浆果赤霉素III制备。10-脱乙酰氧基紫杉醇在对P-388细胞的细胞毒性方面可与紫杉醇媲美，但10-脱氧紫杉醇的细胞毒性比紫杉醇明显更高。
• Process for the preparation of 10-desacetoxybaccatin III
  申请人：Florida State University

  公开号：US05654447A1

  公开（公告）日：1997-08-05

  A process for abstracting a C10 hydroxy, acyloxy or sulfonyloxy substituent from a taxane in which the C10 hydroxy, acyloxy or sulfonyloxy substituted taxane is reacted with samarium diiodide.

  一种从紫杉烷中提取C10羟基、酰氧基或磺酰氧基取代基的过程，其中将C10羟基、酰氧基或磺酰氧基取代的紫杉烷与二碘化钐反应。
• Electrochemical reduction of taxoids: Selective preparation of 9-dihydro-, 10-deoxy- and 10-deacetoxy-taxoids
  作者：Jean-Pierre Pulicani、Jean-Dominique Bourzat、Hervé Bouchard、Alain Commerçon

  DOI：10.1016/s0040-4039(00)73303-x

  日期：1994.7

  The electrochemical reduction of docetaxel in methanol in the presence of ammonium chloride leads to 9 alpha-dihydro-docetaxel 3 and 9 beta-dihydro-docetaxel 4. Under the same conditions, the electrochemical reduction of paclitaxel gives 10-deacetoxy-paclitaxel 7. Calcium chloride as well as magnesium and cerium chloride, and to some extent strontium and lithium chloride, favor IO-dehydroxylation in the docetaxel series. All these docetaxel analogs retain biological activity.
• Synthesis and interactions of 7-deoxy-, 10-deacetoxy, and 10-deacetoxy-7-deoxypaclitaxel with NCI/ADR-RES cancer cells and bovine brain microvessel endothelial cells
  作者：Haibo Ge、Veena Vasandani、Jacquelyn K. Huff、Kenneth L. Audus、Richard H. Himes、Anna Seelig、Gunda I. Georg

  DOI：10.1016/j.bmcl.2005.09.043

  日期：2006.1

  7-Deoxypaclitaxel, 10-deacetoxypaclitaxel and 10-deacetoxy-7-deoxypaclitaxel were prepared and evaluated for their ability to promote assembly of tubulin into microtubules, their cytotoxicity against NCI/ADR-RES cells and for their interactions with P-glycoprotein in bovine brain microvessel endothelial cells. The three compounds were essentially equivalent to paclitaxel in cytotoxicity against NCI/ADR-RES cells. They also appeared to interact with P-glycoprotein in the endothelial cells with the two 10-deacetoxy compounds having less interaction than paclitaxel and 7-deoxypaclitaxel. (c) 2005 Elsevier Ltd. All rights reserved.