2′-O-（苄氧羰基）紫杉醇 | 148930-30-7

• 中文名称: 2′-O-（苄氧羰基）紫杉醇
• 英文名称: 2’-carboxybenzoylpaclitaxel
• 英文别名: 2'-benzyloxycarbonyl-paclixatel；2'-Z-paclitaxel；2'-O-(Benzyloxycarbonyl)taxol；2'-benzyloxycarbonyltaxol；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-15-[(2R,3S)-3-benzamido-3-phenyl-2-phenylmethoxycarbonyloxypropanoyl]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: 148930-30-7
• 化学式: C₅₅H₅₇NO₁₆
• 分子量: 988.055
• InChiKey: VWNYXOYSAFBZTM-XXWNPYBWSA-N

物化性质

• 沸点：
  1020.4±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、DCM、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  72
• 可旋转键数：
  19
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  237
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  2′-O-（苄氧羰基）紫杉醇 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 7-(β-alanyl)paclitaxel
  参考文献：
  名称：

  Antitumor agents. 256. Conjugation of paclitaxel with other antitumor agents: Evaluation of novel conjugates as cytotoxic agents

  摘要：

  Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 2'- or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL-CPT conjugates, 8-10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED50 = 14.8, 3.1, 19.4 nM compared with 55.5 nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8-10 are possible antitumor drug candidates, particularly for prostate cancer. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.051
• 作为产物：
  描述：

  在 palladium on activated charcoal N-碘代丁二酰亚胺 、 4 A molecular sieve 、 氢气 、 N,N-二异丙基乙胺 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 37.0 ℃ 、413.69 kPa 条件下， 反应 7.0h， 生成 2′-O-（苄氧羰基）紫杉醇
  参考文献：
  名称：

  Synthesis and antitumor evaluation of paclitaxel phosphonooxymethyl ethers: a novel class of water soluble paclitaxel pro-drugs

  摘要：

  The synthesis, pharmacokinetic properties, and antitumor evaluation of novel paclitaxel phosphonooxymethyl ether derivatives 8-11 and salts thereof is described. These compounds exhibit improved water solubility as compared to paclitaxel (1) and upon incubation with plasma and alkaline phosphatase they readily release parent drug. The in vivo antitumor evaluation of compounds 8-11 established them as suitable pro-drugs of paclitaxel. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00321-6

文献信息

• Phosphonooxy and carbonate derivatives of taxol
  申请人：Bristol-Myers Squibb Company

  公开号：US05272171A1

  公开（公告）日：1993-12-21

  The present invention is directed to novel taxol derivatives useful as anti-tumor agents. Also provided by this invention is pharmaceutical formulations and methods of treating mammalian tumors with the compounds of this invention.

  本发明涉及新型紫杉醇衍生物，可用作抗肿瘤药物。本发明还提供了药物配方和使用本发明化合物治疗哺乳动物肿瘤的方法。
• Synthesis and Biological Evaluation of a Biotinylated Paclitaxel with an Extra-Long Chain Spacer Arm
  作者：Lev. G. Lis、Mary A. Smart、Anna Luchniak、Mohan L. Gupta、Vadim J. Gurvich

  DOI：10.1021/ml300149z

  日期：2012.9.13

  A biotinylated paclitaxel derivative with an extra-long chain (LC-LC-biotin) spacer arm was synthesized using an improved synthetic reaction sequence. The biotinylated paclitaxel analogue retained excellent microtubule stabilizing activity in vitro. Furthermore, it was shown that this analogue can simultaneously engage streptavidin and the binding site on microtubules, making it suitable for localization

  使用改进的合成反应序列合成了具有超长链（LC-LC-生物素）间隔臂的生物素化紫杉醇衍生物。生物素化的紫杉醇类似物在体外保留了极好的微管稳定活性。此外，该类似物可以同时结合链霉亲和素和微管上的结合位点，使其适用于定位研究或通过链霉亲和素键将紫杉醇连接到固体基质上。
• Fluoro taxols
  申请人：Bristol-Myers Squibb Company

  公开号：US05294637A1

  公开（公告）日：1994-03-15

  This invention relates to a fluorinated taxol of formula I ##STR1## in which R.sup.1 is --COR.sup.z in which R.sup.z is RO-- or R; R.sup.g is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, or a radical of the formula --W--R.sup.x in which W is a bond, C.sub.2-6 alkenediyl, or --(CH.sub.2).sub.t --, in which t is one to six; and R.sup.x is naphthyl, furyl, thienyl or phenyl, and furthermore R.sup.x can be optionally substituted with one to three same or different C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen or --CF.sub.3 groups; R.sup.2 is --OCOR, H, OH, --OR, --OSO.sub.2 R, --OCONR.sup.o R, --OCONHR, --OCOO(CH.sub.2).sub.t R, or --OCOOR; and R and R.sup.o are independently C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.3-6 cycloalkyl, C.sub.2-6 alkynyl, or phenyl, optionally substituted with one to three same or different C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen or --CF.sub.3 groups. Further provided by this invention are pharmaceutical formulations and useful intermediates for the fluorinated taxols of formula I. A method of treating mammalian tumors using a compound of formula I is also provided.

  本发明涉及一种化学式为I的氟化紫杉醇，其中R.sup.1是--COR.sup.z，其中R.sup.z为RO--或R；R.sup.g为C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基，或具有--W--R.sup.x的基团，其中W是键，C.sub.2-6烯二基，或--(CH.sub.2).sub.t--，其中t为1至6；R.sup.x为萘基，呋喃基，噻吩基或苯基，此外R.sup.x还可以选择地用一个至三个相同或不同的C.sub.1-6烷基，C.sub.1-6烷氧基，卤素或--CF.sub.3基团取代；R.sup.2为--OCOR，H，OH，--OR，--OSO.sub.2 R，--OCONR.sup.o R，--OCONHR，--OCOO(CH.sub.2).sub.t R，或--OCOOR；R和R.sup.o分别为C.sub.1-6烷基，C.sub.2-6烯基，C.sub.3-6环烷基，C.sub.2-6炔基，或苯基，可选地用一个至三个相同或不同的C.sub.1-6烷基，C.sub.1-6烷氧基，卤素或--CF.sub.3基团取代。此外，本发明还提供了该化学式I的氟化紫杉醇的药物制剂和有用的中间体。同时也提供了使用化学式I化合物治疗哺乳动物肿瘤的方法。
• 7,8-cyclopropataxanes
  申请人：Bristol-Myers Squibb Company

  公开号：US05254580A1

  公开（公告）日：1993-10-19

  An antitumor compound of formula I ##STR1## in which R.sup.1 is --COR.sup.z in which R.sup.z is t-butyloxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, or phenyl, optionally substituted with one to three same or different C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen or --CF.sub.3 groups; R.sup.2 is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, or a radical of the formula --W--R.sup.x in which W is a bond, C.sub.2-6 alkenediyl, or --(CH.sub.2).sub.t --, in which t is one to six; and R.sup.x is naphthyl, furyl, thienyl or phenyl, and furthermore R.sup.x can be optionally substituted with one to three same or different C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halogen or --CF.sub.3 groups; R.sup.3 is OCOR, --OCOOR, H, or OH; R.sup.4 is hydrogen; or R.sup.3 and R.sup.4 jointly form a carbonyl group; and R is C.sub.1-6 alkyl. Also provided by this invention are pharmaceutical formulations (compositions) and a method of treating mammalian tumors with a compound of formula I.

  公式I的抗肿瘤化合物为 ##STR1## 其中 R.sup.1 为 --COR.sup.z，其中 R.sup.z 为 t-丁氧基，C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基或苯基，可选地取代一个至三个相同或不同的C.sub.1-6烷基，C.sub.1-6烷氧基，卤素或--CF.sub.3基团; R.sup.2 为C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基或公式--W--R.sup.x的基团，其中W为键，C.sub.2-6烯二基或--(CH.sub.2).sub.t --，其中t为1至6；且R.sup.x为萘基，呋喃基，噻吩基或苯基，此外，R.sup.x还可以选择性地取代一个至三个相同或不同的C.sub.1-6烷基，C.sub.1-6烷氧基，卤素或--CF.sub.3基团; R.sup.3为OCOR，--OCOOR，H或OH; R.sup.4为氢; 或R.sup.3和R.sup.4共同形成一个羰基团; 而R为C.sub.1-6烷基。本发明还提供了公式I的化合物的制药配方（组成）和治疗哺乳动物肿瘤的方法。
• The chemistry of taxanes: reaction of taxol and baccatin derivatives with Lewis acids in aprotic and protic media
  作者：Shu-Hui Chen、Stella Huang、Jianmei Wei、Vittorio Farina

  DOI：10.1016/s0040-4020(01)80381-1

  日期：1993.4

  proceed via anchimeric assistance by the C-4 acetate group. Several minor products, including a novel derivative possessing a bridged C-ring, were also isolated. A mechanistic rationale is provided for all compounds formed. When taxol derivatives were treated with Lewis acids in methanol, ester cleavage reactions were observed. We provide conditions that are selective for C-10 acetate cleavage and

  几种路易斯酸被证明可以完全打开紫杉醇和浆果赤霉素衍生物的氧杂环丁烷环。已表明该反应是通过C-4乙酸酯基团通过邻氨基苯甲酸协助进行的。还分离了几种次要产物，包括具有桥C环的新型衍生物。提供了所形成的所有化合物的机械原理。当在甲醇中用路易斯酸处理紫杉醇衍生物时，观察到酯裂解反应。我们提供对C-10乙酸酯裂解和C-13侧链甲醇裂解具有选择性的条件。