10-deacetyl-2'-(tert-butyldimethylsilyl)-7-(triethylsilyl) paclitaxel | 162809-97-4

• 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-deacetyl-2'-(tert-butyldimethylsilyl)-7-(triethylsilyl) paclitaxel
• 英文别名: 2'-(tert-butyldimethylsilyl)-10-deacetyl-7-(triethylsilyl)taxol；2'-O-(tert-butyldimethylsilyl)-10-deacetyl-7-O-triethylsilylpaclitaxel；2'-O-TBDMS-7-O-TES-10-deacetyl-paclitaxel；2'-O-TBS,7-O-TES,10-O-deacetyl-paclitaxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 162809-97-4
• 化学式: C₅₇H₇₇NO₁₃Si₂
• 分子量: 1040.41
• InChiKey: VVYVIPSAMZTUCH-VSWPBMBDSA-N

物化性质

• 熔点：
  158-161 °C
• 沸点：
  956.3±65.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.22
• 重原子数：
  73
• 可旋转键数：
  20
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  193
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  10-deacetyl-2'-(tert-butyldimethylsilyl)-7-(triethylsilyl) paclitaxel 在 N-甲基吲哚酮 、 四丙基高钌酸铵 作用下， 以 二氯甲烷 为溶剂， 以79%的产率得到2'-O-TBDMS-7-O-TES-9,10-diketo-paclitaxel
  参考文献：
  名称：

  新型C-9和C-10修饰的生物活性紫杉烷的合成

  摘要：

  已经开发了一种用于合成迄今未报道的C-9和C-10修饰的紫杉烷的方法。这些类似物对B 16黑色素瘤细胞表现出优异的细胞毒性。

  DOI：

  10.1016/0040-4039(95)00208-t
• 作为产物：
  描述：

  7-表-10-脱乙酰基紫杉醇 生成 10-deacetyl-2'-(tert-butyldimethylsilyl)-7-(triethylsilyl) paclitaxel
  参考文献：
  名称：

  The Chemistry of the Taxane Diterpene:  Stereoselective Reductions of Taxanes

  摘要：

  Stereoselective reductions of taxanes are detailed. Chelation-controlled reductions employing SmI2 are described for the stereoselective reduction of the 9-keto functionality of the diterpene moiety of several taxanes. In all cases the 9 beta-hydroxy stereochemistry was obtained exclusively. In addition to C9 reduction, partial C10-deoxygenation via beta-elimination was observed. Lower reaction temperatures favored the reduction pathway without beta-elimination. Acetic acid as the proton source gave higher yields and cleaner reaction products. This chemistry provided access to taxanes with 9 beta-hydroxy, 10 beta-hydroxy stereochemistry. Evidence is presented, suggesting that chelation of samarium with the 7 beta-hydroxyl group is required for the reduction of the C9 ketone moiety. The synthesis of paclitaxel analogues, possessing the 9 alpha-hydroxy, 10 alpha-hydroxy stereochemistry was also achieved. Reduction of the 10-ketone group of 10-oxopaclitaxel employing NaBH4 produced 10-deacetyl-10-epipaclitaxel stereoselectively. Using an excess of NaBH4 in this reaction gave exclusively the 9 alpha-hydroxy, 10 alpha-hydroxy paclitaxel analogue.

  DOI：

  10.1021/jo981194s

文献信息

• [EN] THIOLATED PACLITAXELS FOR REACTION WITH GOLD NANOPARTICLES AS DRUG DELIVERY AGENTS<br/>[FR] PACLITAXELS THIOLÉS DESTINÉS À RÉAGIR AVEC DES NANOPARTICULES D'OR, SERVANT D'AGENTS DE DISTRIBUTION DE MÉDICAMENTS
  申请人：VIRGINIA TECH INTELL PROP

  公开号：WO2009062138A1

  公开（公告）日：2009-05-14

  Thioloated taxane derivatives are linked to colloidal metal particles such as gold nanoparticles for use as antitumor agents. The antitumor agents may be targeted to tumors.

  硫代納二烯衍生物与金纳米粒子等胶体金属颗粒相结合，用作抗肿瘤药剂。这些抗肿瘤药剂可以针对肿瘤。
• Synthesis and microtubule binding of fluorescent paclitaxel derivatives
  作者：Erkan Baloglu、David G.I Kingston、Pruthvi Patel、Sabarni K Chatterjee、Susan L Bane

  DOI：10.1016/s0960-894x(01)00453-x

  日期：2001.9

  The preparation of two new fluorescent derivatives of paclitaxel in which the fluorophore is bonded to paclitaxel at the C-10 position is reported. Both analogues, 10-deacetyl-10-(m-aminobenzoyl)paclitaxel (1, BTax) and 10-deacetyl-10-[7-(diethylamino) coumarin-3-carbonyl]paclitaxel (2, CTax) retain good activity as promoters of in vitro tubulin assembly. Microtubule binding enhances the emission intensity

  报道了两种新的紫杉醇荧光衍生物的制备，其中荧光团在C-10位键合至紫杉醇。10-去乙酰基-10-（间氨基苯甲酰基）紫杉醇（1，BTax）和10-去乙酰基-10- [7-（二乙基氨基）香豆素-3-羰基]紫杉醇（2，CTax）的类似物都具有良好的启动子活性。的微管蛋白组装。微管结合提高了两种探针的发射强度。
• Synthesis of 7- and 10-spermine conjugates of paclitaxel and 10-deacetyl-paclitaxel as potential prodrugs
  作者：Arturo Battaglia、Andrea Guerrini、Eleonora Baldelli、Gabriele Fontana、Greta Varchi、Cristian Samorì、Ezio Bombardelli

  DOI：10.1016/j.tetlet.2006.02.108

  日期：2006.4

  chemical modification into taxol skeleton in order to increase drug selectivity toward tumor cells. The cytotoxic activity of these conjugates was evaluated in MCF7 and MCF7-R cell lines. The observed low cytotoxicity suggests that these conjugates could act as potential prodrugs.

  已经开发了在紫杉醇和10-去乙酰基紫杉醇的7和10位带有线性多胺精胺的两种紫杉醇类似物的有效合成方法。这些多胺-紫杉醇-缀合物被分离为水溶性二氟化物盐。本工作的目的是将化学修饰引入紫杉酚骨架中，以增加对肿瘤细胞的药物选择性。在MCF7和MCF7-R细胞系中评估了这些缀合物的细胞毒性活性。观察到的低细胞毒性表明这些缀合物可以充当潜在的前药。
• Biologically Active Taxane Analogs and Methods of Treatment
  申请人：Lamb Rodger

  公开号：US20080207743A1

  公开（公告）日：2008-08-28

  The present application relates to new taxane analogs, pharmaceutical compositions comprising such analogs and methods of treating cancer comprising such compositions. The compounds according to the present application have the general formula: wherein R 1 and R 2 are each selected from H, alkyl, alkenyl or aryl; R 3 is hydroxyl or OP 1 ; R 4 is OH or R 7 COO; R 7 is alkyl, alkenyl or aryl, R 8 and R 9 are each independently selected from H, alkyl or alkenyl. The compounds of the present application may particularly be 9,10-α,α-OH taxane analogs that are formed by a process starting with a standard taxane as the starting compound.

  本申请涉及新的紫杉醇类似物，包括这种类似物的药物组合物以及包括这种组合物的治疗癌症的方法。根据本申请的化合物具有一般公式：其中R1和R2分别选自H、烷基、烯基或芳基；R3是羟基或OP1；R4是OH或R7COO；R7是烷基、烯基或芳基，R8和R9分别独立选自H、烷基或烯基。本申请的化合物可能特别是通过以标准紫杉醇作为起始化合物开始的过程形成的9,10-α,α-OH紫杉醇类似物。
• C-10 CARBAMATES OF TAXANES
  申请人：Ballatore Carlo

  公开号：US20090306014A1

  公开（公告）日：2009-12-10

  Provided herein are C-10 taxane carbamates and pharmaceutically acceptable derivatives thereof. In certain embodiments, provided herein are compounds, compositions and methods for treating cancer and taupathy.

  本文提供了C-10紫杉烷氨甲酸酯及其药学上可接受的衍生物。在某些实施方式中，提供了化合物、组合物和治疗癌症和tau病理的方法。