2'-O-TBDMS-7-O-TES-9,10-diketo-paclitaxel | 162664-54-2

• 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: 2'-O-TBDMS-7-O-TES-9,10-diketo-paclitaxel
• 英文别名: 2'-O-TBDMS-7-O-TES-9,10-diketopaclitaxel；2'-TBS-10-deacetyl-7-TES-10-ketopaclitaxel；[(1S,2S,3R,4S,7R,9S,10S,15S)-4-acetyloxy-15-[(2R,3S)-3-benzamido-2-[tert-butyl(dimethyl)silyl]oxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11,12-dioxo-9-triethylsilyloxy-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 162664-54-2
• 化学式: C₅₇H₇₅NO₁₃Si₂
• 分子量: 1038.39
• InChiKey: KVBZPXZXQXPBHH-MOOBGUANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.43
• 重原子数：
  73
• 可旋转键数：
  20
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  190
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2'-O-TBDMS-7-O-TES-9,10-diketo-paclitaxel 在 对甲苯磺酸 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 锂硼氢 、 四丁基氟化铵 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 52.0h， 生成 3-O-benzyl 5-O-[(1R,2S,5R,7S,11R,12S,15S,17S,18S,19S)-2,12-diacetyloxy-18-benzoyloxy-17-hydroxy-9-(4-methoxyphenyl)-14,19,20,20-tetramethyl-4,8,10-trioxapentacyclo[9.7.1.113,17.02,5.07,19]icos-13-en-15-yl] (4S)-2-(4-methoxyphenyl)-4-(2-methylpropyl)-1,3-oxazolidine-3,5-dicarboxylate
  参考文献：
  名称：

  Biologically Active Taxane Analogs and Methods of Treatment

  摘要：

  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。

  公开号：

  US20080207743A1
• 作为产物：
  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

文献信息

• The Chemistry of the Taxane Diterpene:  Stereoselective Reductions of Taxanes
  作者：Gunda I. Georg、Geraldine C. B. Harriman、Apurba Datta、Syed Ali、Zacharia Cheruvallath、Dinah Dutta、David G. Vander Velde、Richard H. Himes

  DOI：10.1021/jo981194s

  日期：1998.11.1

  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.
• [EN] 9,10-alpha,alpha-OH-TAXANE ANALOGS AND METHODS FOR PRODUCTION THEREOF<br/>[FR] ANALOGUES DE 9,10-<supplemental>20050714</supplemental>US5635531ACHEN SHU-HUI [US]19970603XX
  申请人：TAPESTRY PHARMACEUTICALS INC

  公开号：WO2005030150A3

  公开（公告）日：2005-07-14
• Synthesis of a novel C-10 spiro-epoxide of paclitaxel
  作者：Michael A. Walker、Timothy D. Johnson、Stella Huang、Dolatorai M. Vyas、John F. Kadow

  DOI：10.1016/s0960-894x(01)00280-3

  日期：2001.7

  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.
• WO2008/121476
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• WO2008/106621
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