[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis(phenylmethoxycarbonyloxy)-15-[(2R,3S)-3-phenyl-3-(phenylmethoxycarbonylamino)-2-(phenylmethoxymethoxy)propanoyl]oxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate | 196302-75-7

• 英文名称: [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis(phenylmethoxycarbonyloxy)-15-[(2R,3S)-3-phenyl-3-(phenylmethoxycarbonylamino)-2-(phenylmethoxymethoxy)propanoyl]oxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 196302-75-7
• 化学式: C₇₀H₇₁NO₁₉
• 分子量: 1230.33
• InChiKey: MOERMNWIQZBGJZ-RGKSOCSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.1
• 重原子数：
  90
• 可旋转键数：
  29
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  253
• 氢给体数：
  2
• 氢受体数：
  19

反应信息

• 作为反应物：
  描述：

  [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis(phenylmethoxycarbonyloxy)-15-[(2R,3S)-3-phenyl-3-(phenylmethoxycarbonylamino)-2-(phenylmethoxymethoxy)propanoyl]oxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 在 palladium 10% on activated carbon 盐酸 、 氢气 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 10-去乙酰基-N-去苯甲酰基紫杉醇
  参考文献：
  名称：

  WO2007/73383

  摘要：

  公开号：
• 作为产物：
  描述：

  C-7,C-10-dibenzyloxycarbonyl-10-deacetyl baccatin III 、 benzyl N-[(1S,2R)-3-fluoro-3-oxo-1-phenyl-2-(phenylmethoxymethoxy)propyl]carbamate 在 4-吡咯烷基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以86%的产率得到[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis(phenylmethoxycarbonyloxy)-15-[(2R,3S)-3-phenyl-3-(phenylmethoxycarbonylamino)-2-(phenylmethoxymethoxy)propanoyl]oxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  参考文献：
  名称：

  WO2007/73383

  摘要：

  公开号：

文献信息

• [EN] NEW EFFICIENT METHODS FOR THE SYNTHESIS OF TAXANE DERIVATIVES SUCH AS DOCETAXEL AND THEIR STRUCTURAL ANALOGOUS, AND A METHOD FOR THE PREPARATION THEREOF<br/>[FR] NOUVEAUX PROCÉDÉS EFFICACES POUR LA SYNTHÈSE DE DÉRIVÉS DE TYPE TAXANE TELS QUE LE DOCÉTAXEL ET LEURS ANALOGUES STRUCTURAUX, ET PROCÉDÉ DE PRÉPARATION DE CES DERNIERS
  申请人：KARIMIAN KHASHAYAR

  公开号：WO2016098015A1

  公开（公告）日：2016-06-23

  The present invention relates to a novel process for the preparation of taxanes such as Docetaxel, a very important anticancer drug. Docetaxel 1 is a clinically well-established anti -mitotic chemotherapy medication used mainly for the treatment of breast, ovarian and non-small cell lung cancer. In this work we introduce an efficient and simple process for producing Docetaxel 1 (vide infra), including the following steps: a) hydroxyl acylation reaction of 10-DAB-III with chloroacetic acid to obtaine compound 2; b) condensation reaction of compounds 2 and 3 to obtain compound 4; c) deprotection of protecting group paramethoxy phenyl (PMP) protecting group to obtain compound 5 d) deprotection of protecting group Rl of compound 5 to prepare Docetaxel 1; wherein, Rl is, among other acetylation reagents, chloroacetyl chloride, R2 is, among other ketones and aldehydes, paramethoxy phenyl (PMP), and R3 is, among other alkanes, tert-butyl e) subjecting the crude Docetaxel to fast filtration over a short silica gel filter to obtain anhydrous Docetaxel of > 95% purity f) crystallizing the anhydrous Docetaxel of step e) to obtain pharmaceutical grade Docetaxel trihydrate. In the methods for preparation of the present invention, the protective groups used are easily removed, the purification of the intermediates is convenient, the cost of production is reduced, the steps of reaction are fewer, the yield and the purity are higher, and the processes can be scaled to commercial scale production. Another important aspect of the present invention is the preparation of pharmaceutical grade Docetaxel without resorting to chromatography.

  这项发明涉及一种新型的紫杉醇类药物如多西紫杉醇（Docetaxel）的制备过程。多西紫杉醇是一种临床上已经确立的抗肿瘤药物，主要用于治疗乳腺癌、卵巢癌和非小细胞肺癌。在这项工作中，我们介绍了一种高效简单的多西紫杉醇制备过程，包括以下步骤：a）10-DAB-III与氯乙酸的羟基酰化反应得到化合物2；b）化合物2和3的缩合反应得到化合物4；c）去保护基对甲氧基苯基（PMP）保护基的去保护反应得到化合物5；d）去除化合物5的保护基R1以制备多西紫杉醇；其中，R1是氯乙酰氯等乙酰化试剂，R2是对甲氧基苯基（PMP）等酮和醛，R3是叔丁基等烷基；e）将粗多西紫杉醇快速过滤于短硅胶过滤器上，得到纯度>95%的无水多西紫杉醇；f）结晶化步骤e）的无水多西紫杉醇，得到药用级多西紫杉醇三水合物。在本发明的制备方法中，所使用的保护基易于去除，中间体的纯化方便，生产成本降低，反应步骤较少，产率和纯度较高，并且这些过程可以扩展到商业规模生产。本发明的另一个重要方面是制备药用级多西紫杉醇而无需使用色谱法。